acetylcysteine
type: AminoAcidMonograph
pref label:
  en: Acetylcysteine
  ja: アセチルシステイン
monograph id: JP18-acetylcysteine
publisher: JP
status: Official
version: 18
molecular formula: C5H9NO3S
molecular weight: 163.19
definition:
  en: Acetylcysteine contains not less than 99.
appearance:
  en: Acetylcysteine occurs as white, crystals or crys-talline powder. It is freely soluble in water and in ethanol (99.5). It dissolves in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Acetylcysteine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋21.0 – ＋27.09Weigh accu-rately an amount of Acetylcysteine, equivalent to about 2.5 g calculated on the dried basis, and dissolve with 2 mL of a so-lution of disodium dihydrogen ethylenediamine tetraacetate dihydrate (1 in 100) and 15 mL of a solution of sodium hy-droxide (1 in 25). To this solution add a solution, prepared by adjusting the pH to 7.0 of 500 mL of a solution of potas-sium dihydrogen phosphate (17 in 125) with sodium hydrox-ide TS and adding water to make 1000 mL, to make exactly 50 mL. Determine the optical rotation of this solution using ‌JP XVIII Official Monographs / Aciclovir 407 a 100-mm cell.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 0.40 g of Acetyl-cysteine in 25 mL of sodium hydroxide TS, add 4 mL of hydrogen peroxide (30), heat in a water bath for 45 minutes, and cool. Then add 5 mL of nitric acid, add water to make 50 mL, and perform the test using this solution as the test so-lution. Prepare the control solution with 0.45 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.040z). Sulfate <1.14>—Perform the test with 0.8 g of Acetyl- cysteine. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.030z). Ammonium <1.02>—Perform the test with 0.10 g of Acetylcysteine, using the distillation under reduced pressure. Prepare the control solution with 2.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Dissolve 1.0 g of Acetyl- cysteine in 40 mL of water, add 3 mL of sodium hydroxide TS, 2 mL of dilute acetic acid and water to make 50 mL, and perform the test using this solution as the test solution. Pre-pare the control solution as follows: To 1.0 mL of Standard Lead Solution add 2 mL of dilute acetic acid and water to make 50 mL (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of Acetylcysteine according to Method 1, and perform the test according to Method A. Prepare the control solution with 1.0 mL of Standard Iron Solution (not more than 10 ppm). Related substances—Dissolve 50 mg of Acetyl-cysteine in 25 mL of the mobile phase, and use this solution as the sample solution. The sample solution is prepared before using. Perform the test with 10 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the following conditions, determine each peak area by the automatic integration method, and calculate their amounts by the area percentage method: the area of the peak other than acetylcysteine is not more than 0.3z, and the total area of the peak other than acetylcysteine is not more than 0.6z. Operating conditions— Detector: An ultraviolet absorpti…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Acetylcysteine, place it in a stoppered flask, dissolve in 20 mL of water, add 4 g of potassium iodide and 5 mL of dilute hydrochloric acid, then add exactly 25 mL of 0.05 mol/L iodine VS, stop-per tightly, allow to stand for 20 minutes in an ice cold water in the dark, and titrate <2.50> the excess of iodine with 0.1 mol/L sodium thiosulfate VS (indicator: 1 mL of starch TS). Perform a blank determination in the same manner. Each mL of 0.05 mol/L iodine VS ＝ 16.32 mg of C5H9NO3S
storage conditions:
  en: Containers—Tight containers.

cycloserine
type: AminoAcidMonograph
pref label:
  en: Cycloserine
  ja: サイクロセリン
monograph id: JP18-cycloserine
publisher: JP
status: Official
version: 18
molecular formula: C3H6N2O2
molecular weight: 102.09
definition:
  en: Cycloserine contains not less than 950 mg (potency) and not more than 1020 mg (potency) per mg, calcu-lated on the dried basis.
appearance:
  en: Cycloserine occurs as white to light yellow-white, crystals or crystalline powder. It is soluble in water, and sparingly soluble in ethanol (95). ‌824
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Cycloserine, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum or the spectrum of previously dried Cycloserine RS: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋108 – ＋1149(2.5 g calcu-lated on the dried basis, 2 mol/L sodium hydroxide TS, 50 mL, 100 mm). pH <2.54> Dissolve 1.0 g of Cycloserine in 20 mL of water: the pH of the solution is between 5.0 and 7.4.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Cycloserine according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Condensation products—Dissolve 20 mg of Cycloser-ine in sodium hydroxide TS to make exactly 50 mL, and de-termine the absorbance of this solution at 285 nm as directed Cyproheptadine Hydrochloride Hydrate

ethyl-l-cysteine-hydrochloride
type: AminoAcidMonograph
pref label:
  en: Ethyl L-Cysteine Hydrochloride
  ja: L-エチルシステイン塩酸塩
monograph id: JP18-ethyl-l-cysteine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C5H11NO2S.HCl
molecular weight: 185.67
cas number: 868-59-7
appearance:
  en: Ethyl L-Cysteine Hydrochloride occurs as white, crystals or crystalline powder. It has a characteristic odor, and has a bitter taste at first with a burning aftertaste. It is very soluble in water, and freely soluble in ethanol (95). Melting point: about 1269C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of Ethyl L-Cysteine Hydrochloride as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. (2) A solution of Ethyl L-Cysteine Hydrochloride (1 in 20) responds to Qualitative Tests <1.09> (1) for chloride. D Optical rotation <2.49> [a]20: －10.0 – －13.09(after dry-ing, 2.0 g, 1 mol/L hydrochloric acid TS, 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfate <1.14>—Perform the test with 0.6 g of Ethyl L-Cysteine Hydrochloride. Prepare the the control so-lution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Heavy metals <1.07>—Proceed with 1.0 g of Ethyl L-Cysteine Hydrochloride according to Method 1, and per- form the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Conduct this procedure rapidly. Dissolve 0.05 g each of Ethyl L-Cysteine Hydrochloride and N-ethylmaleimide in 5 mL of mobile phase, allow to stand for 30 minutes, and use this solution as the sample solution. Pipet 3 mL of the sample solution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 2 mL each of the sam-ple solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi-tions. Determine each peak area of these solutions by the automatic integration method: a peak area obtained from the sample solution with the relative retention time to ethyl L-cysteine-N-ethylmaleimide complex from the standard so-lution being about 0.7 is not larger than the peak area of ethyl L-cysteine-N-ethylmaleimide complex from the stand-ard solution. Each area of all peaks other than ethyl L-cysteine-N-ethylmaleimide complex and N-ethylmaleimide from the sample solution is not larger than 1/3 times the peak area of ethyl L-cysteine N-ethylmaleimide complex from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 250 nm). Column: A stainless steel column about 6 mm in inside di-ameter and about 15 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of 0.02 mol/L potassium dihy-drogenphoshate TS and acetonitrile (2:1). Flow rate: Adjust so that the retention time …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of Ethyl L-Cysteine Hydrochloride, previously dried, transfer into a glass-stoppered flask, and dissolve in 10 mL of water previously freshly boiled and cooled to a temperature not exceeding 59C in a stream of nitrogen. Add exactly 20 mL of 0.05 mol/L iodine VS, previously cooled to a temperature not exceeding 59C, and allow to stand for 30 seconds, then titrate <2.50> with 0.1 mol/L sodium thiosulfate VS, on cool-ing below 59C (indicator: 1 mL of starch TS). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.05 mol/L iodine VS ＝ 18.57 mg of C5H11NO2S.HCl
storage conditions:
  en: Containers—Tight containers.

glycine
type: AminoAcidMonograph
pref label:
  en: Glycine
  ja: グリシン
monograph id: JP18-glycine
publisher: JP
status: Official
version: 18
molecular formula: C2H5NO2
molecular weight: 75.07
definition:
  en: Glycine, when dried, contains not less than 98.
appearance:
  en: Glycine occurs as white, crystals or crystalline powder. It has a sweet taste. It is freely soluble in water and in formic acid, and practi-cally insoluble in ethanol (95). It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Glycine, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry Gonadorelin Acetate
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 80 mg of Glycine, previ-ously dried, dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 7.507 mg of C2H5NO2
storage conditions:
  en: Containers—Well-closed contain-ers.

l-alanine
type: AminoAcidMonograph
pref label:
  en: L-Alanine
  ja: L-アラニン
monograph id: JP18-l-alanine
publisher: JP
status: Official
version: 18
molecular formula: C3H7NO2
molecular weight: 89.09
definition:
  en: L-Alanine, when dried, contains not less than 98.
appearance:
  en: L-Alanine occurs as white, crystals or crystal-line powder. It has a slightly sweet taste. It is freely soluble in water and in formic acid, and practi-cally insoluble in ethanol (99.5). It dissolves in 6 mol/L hydrochloric acid TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Alanine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋13.5 – ＋15.59(after dry-ing, 2.5 g, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> Dissolve 1.0 g of L-Alanine in 20 mL of water: the pH of the solution is between 5.7 and 6.7.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of L-Alanine in 10 mL of water: the solution is clear and colorless. Chloride <1.03>—Perform the test with 0.5 g of L-Alanine. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Alanine. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Alanine. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 1.0 g of L-Alanine according to Method 1, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of L-Alanine according to Method 1, and perform the test according to Method A. Prepare the control solution with 1.0 mL of Standard Iron Solution (not more than 10 ppm). Related substances—Weigh accurately about 0.5 g of L-Alanine, dissolve in 0.5 mL of hydrochloric acid and water to make exactly 100 mL. Pipet 10 mL of this solution, add 0.02 mol/L hydrochloric acid TS to make exactly 50 mL, and use this solution as the sample solution. Separately, accurately measure 2.5 mmol amounts of L-aspartic acid, L-threonine, L-serine, L-glutamic acid, glycine, L-alanine, L-cystine, L-valine, L-methionine, L-isoleucine, L-leucine, L-tyrosine, L-phenylalanine, L-lysine hydrochloride, ammo-nium chloride, L-histidine and L-arginine, dissolve in 0.1 mol/L hydrochloric acid TS to make exactly 1000 mL, and use this solution as the standard stock solution. Pipet 5 mL of the standard stock solution, add 0.02 mol/L hydrochloric acid TS to make exactly 100 mL. Pipet 4 mL of this solution, add 0.02 mol/L hydrochloric acid TS to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution …

l-arginine-hydrochloride
type: AminoAcidMonograph
pref label:
  en: L-Arginine Hydrochloride
  ja: L-アルギニン塩酸塩
monograph id: JP18-l-arginine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C6H14N4O2.HCl
molecular weight: 210.66
cas number: 1119-34-2
definition:
  en: L-Arginine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: L-Arginine Hydrochloride occurs as white, crystals or crystalline powder. It is odorless, and has a slight, characteristic taste. It is freely soluble in water and in formic acid, and very slightly soluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spectrum of L-Arginine Hydrochloride, previously dried, as directed in the potassium bromide disk method under In-frared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. (2) A solution of L-Arginine Hydrochloride (1 in 50) responds to the Qualitative Tests <1.09> for chloride. D Optical rotation <2.49> [a]20: ＋21.5 – ＋23.59(after dry-ing, 2 g, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> Dissolve 1.0 g of L-Arginine Hydrochloride in 10 mL of water: the pH of this solution is between 4.7 and 6.2.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of L-Arginine Hydrochloride in 10 mL of water: the solution is clear and colorless. Sulfate <1.14>—Perform the test with 0.6 g of L-Arginine Hydrochloride. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of ‌L-Arginine Hydrochloride, using the distillation under reduced pressure. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z).‌ Heavy metals <1.07>—Proceed with 1.0 g of L-Arginine Hydrochloride according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of L-Arginine Hydrochloride according to Method 1, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.20 g of L-Arginine Hydrochloride in 10 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add water to make exactly 10 mL. Pipet 1 mL of this solu-tion, add water to make exactly 25 mL, and use this solution as the standard solution. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethanol (99.5), water, 1-butanol and ammonia water (28) (2:1:1:1) to a distance of about 10 cm, and dry the plate at 1009C for 30 minutes. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate, and heat the plate at 809C for 5 minutes: the spots other than the principal spot obtained from the sample solu-tion are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.20z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of L-Arginine Hydro-chloride, previously dried, dissolve in 2 mL of formic acid, add exactly 15 mL of 0.1 mol/L perchloric acid VS, and heat on a water bath for 30 minutes. After cooling, add 45 mL of acetic acid (100), and titrate <2.50> the excess perchloric acid with 0.1 mol/L sodium acetate VS (potentiometric titration). Perform a blank determination in the same manner. Each mL of 0.1 mol/L perchloric acid VS ＝ 10.53 mg of C6H14N4O2.HCl
storage conditions:
  en: Containers—Tight containers.

l-arginine
type: AminoAcidMonograph
pref label:
  en: L-Arginine
  ja: L-アルギニン
monograph id: JP18-l-arginine
publisher: JP
status: Official
version: 18
molecular formula: C6H14N4O2
molecular weight: 174.2
definition:
  en: L-Arginine, when dried, contains not less than 98.
appearance:
  en: L-Arginine occurs as white, crystals or crystal-line powder. It has a characteristic odor. It is freely soluble in water and in formic acid, and practi-cally insoluble in ethanol (99.5). It dissolves in dilute hydrochloric acid. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of previously dried L-Arginine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋26.9 – ＋27.99(after dry-ing, 2 g, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> The pH of a solution prepared by dissolving 1.0 g of L-Arginine in 10 mL of water is between 10.5 and 12.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution ob-tained by dissolving 1.0 g of L-Arginine in 10 mL of water is clear and colorless. Chloride <1.03>—Perform the test with 0.5 g of L-Arginine. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Arginine. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Arginine, using the distillation under reduced pressure. Prepare the control solution with 5.0 mL of Standard Am-monium Solution (not more than 0.02z). Heavy metals <1.07>—Dissolve 2.0 g of L-Arginine in 30 mL of water, add 1 drop of phenolphthalein TS, neutral- ize with dilute hydrochloric acid, add 2 mL of dilute acetic acid and water to make 50 mL, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of L-Arginine according to Method 1, and perform the test according to Method A. Prepare the control solution with 1.0 mL of Standard Iron Solution (not more than 10 ppm). Related substances—Dissolve 0.10 g of L-Arginine in 10 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add water to make exactly 50 mL. Pipet 2 mL of this solution, add water to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 2-propanol and ammonia solution (28) (7:3) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly ninhydrin-butanol TS on the plate, and heat the plate at 809C for 10 minutes: the spot other than the principal spot obtained from the sample solut…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 80 mg of L-Arginine, previ-ously dried, dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 8.710 mg of C6H14N4O2
storage conditions:
  en: Containers—Tight containers.

l-cysteine-hydrochloride-hydrate
type: AminoAcidMonograph
pref label:
  en: L-Cysteine Hydrochloride Hydrate
  ja: L-システイン塩酸塩水和物
monograph id: JP18-l-cysteine-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C3H7NO2S.HCl.H2O
molecular weight: 175.63
cas number: 7048-04-6
definition:
  en: L-Cysteine Hydrochloride Hydrate contains not less than 98.
appearance:
  en: L-Cysteine Hydrochloride Hydrate occurs as white, crystals or crystalline powder. It has a characteristic odor and a strong acid taste. It is very soluble in water, and soluble in ethanol (99.5). It dissolves in 6 mol/L hydrochloric acid TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of L-Cysteine Hydrochloride Hydrate as directed in the potassium chloride disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. (2) To 10 mL of a solution of L-Cysteine Hydrochloride Hydrate (1 in 50) add 1 mL of hydrogen peroxide (30), heat on a water bath for 20 minutes, and cool: the solution re-sponds to Qualitative Tests <1.09> (2) for chloride. D Optical rotation <2.49> [a]20: ＋6.0 – ＋7.59(2 g, calculated on the dried basis, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> The pH of a solution prepared by dissolving 1.0 g of L-Cysteine Hydrochloride Hydrate in 100 mL of water is between 1.3 and 2.3.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution ob-tained by dissolving 1.0 g of L-Cysteine Hydrochloride Hy-drate in 10 mL of water is clear and colorless. Sulfate <1.14>—Dissolve 0.8 g of L-Cysteine Hydro-chloride Hydrate in 30 mL of water and 3 mL of dilute hy- drochloric acid, and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the con-trol solution as follows: To 0.35 mL of 0.005 mol/L sulfuric acid VS add 3 mL of dilute hydrochloric acid and water to make 50 mL. To both of the test solution and the control solution add 4 mL of barium chloride TS (not more than 0.021z). Ammonium <1.02>—Perform the test with 0.25 g of L-Cysteine Hydrochloride Hydrate using the distillation under reduced pressure. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 1.0 g of L-Cysteine Hydrochloride Hydrate according to Method 4, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of L-Cysteine Hydrochloride Hydrate according to Method 1, and perform the test according to Method A. Prepare the control solution with 1.0 mL of Standard Iron Solution (not more than 10 ppm). Related substances—Dissolve 0.10 g of L-Cysteine Hydrochloride Hydrate in N-ethylmaleimide solution (1 in 50) to make 10 mL, allow to stand for 30 minutes, and use this solution as the sample solution. Pipet 1 mL of the sam-ple solution, add water to make exactly 10 mL. Pipet 1 mL of this solution, add water to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-Layer Chromatogra-phy <2.03>. Spot 5 mL each of the sample solution and stand-ard solution on a plate of silica gel for thin-layer chromatog-raphy. Then develop with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of L-Cysteine Hydro-chloride Hydrate, place in a glass-stoppered flask, and dis-solve in 20 mL of water. Dissolve 4 g of potassium iodide in this solution, soak immediately in ice cold water, add 5 mL of dilute hydrochloric acid and exactly 25 mL of 0.05 mol/L iodine VS, allow to stand for 20 minutes in a dark place, titrate <2.50> the excess of iodine with 0.1 mol/L sodium thiosulfate VS (indicator: starch TS). Perform a blank deter-mination in the same manner, and make any necessary cor-rection. Each mL of 0.05 mol/L iodine VS ＝ 15.76 mg of C3H7NO2S.HCl
storage conditions:
  en: Containers—Tight containers.

l-cysteine
type: AminoAcidMonograph
pref label:
  en: L-Cysteine
  ja: L-システイン
monograph id: JP18-l-cysteine
publisher: JP
status: Official
version: 18
molecular formula: C3H7NO2S
molecular weight: 121.16
appearance:
  en: L-Cysteine occurs as white crystals or a white crystalline powder. It has a characteristic odor and a pun-gent taste. It is freely soluble in water, and practically insoluble in ethanol (99.5). It dissolves in 1 mol/L hydrochloric acid TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Cysteine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋8.0 – ＋10.09(2 g calcu-lated on the dried basis, 1 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> The pH of a solution prepared by dissolving 1.25 g of L-Cysteine in 50 mL of water is 4.7 to 5.7.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of L-Cysteine in 20 mL of water: the solution is clear and colorless. Chloride <1.03>—Dissolve 0.30 g of L-Cysteine in 10 mL of diluted nitric acid (1 in 4), add 10 mL of hydrogen peroxide (30), heat for 20 minutes in a boiling water bath, cool, and then add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.35 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.041z). Sulfate <1.14>—Dissolve 0.6 g of L-Cysteine in 30 mL of water and 3 mL of dilute hydrochloric acid, and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: To 0.35 mL of 0.005 mol/L sulfuric acid VS add 3 mL of dilute hydrochloric acid and water to make 50 mL. Prepare the test mL of Standard Iron Solution (not more than 10 ppm). Related substances—Dissolve 0.10 g of L-Cysteine in N-ethylmaleimide solution (1 in 50) to make exactly 10 mL, leave for 30 minutes, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 10 mL, pipet 1 mL of this solution, add water to make exactly 50 mL, and use this solution as the standard solution (1). Separately, dissolve 0.10 g of L-cystine in 0.5 mol/L hydrochloric acid TS to make exactly 20 mL. Pipet 1 mL of this solution, add water to make 100 mL, and use this solution as the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 10 mL each of the sample solution and standard solutions (1) and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, water, and acetic acid (100) (3:1:1) to a distance of about 10 cm, and dry the plate for 30 minutes at 809C. Spray the plate evenly with a solution of ninhydrin in a mix-ture of methanol and acetic acid (100) (97:3) (1 in 100), and then heat at 809C for 10 minutes: the spo…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of L-Cysteine, place it in a stoppered flask, and dissolve in 20 mL of water. Dis-solve 4 g of potassium iodide in this solution, immediately place in ice cold water, add 5 mL of dilute hydrochloric acid and exactly 25 mL of 0.05 mol/L iodine VS, leave in a dark place for 20 minutes, and then titrate <2.50> an excess amount of iodine with 0.1 mol/L sodium thiosulfate VS (in-dicator: starch TS). Perform a blank determination in the same manner. Each mL of 0.05 mol/L iodine VS ＝ 12.12 mg of C3H7NO2S
storage conditions:
  en: Containers—Tight containers.

l-histidine-hydrochloride-hydrate
type: AminoAcidMonograph
pref label:
  en: L-Histidine Hydrochloride Hydrate
  ja: L-ヒスチジン塩酸塩水和物
monograph id: JP18-l-histidine-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
cas number: 5934-29-2
definition:
  en: L-Histidine Hydrochloride Hydrate contains not less than 99.
appearance:
  en: L-Histidine Hydrochloride Hydrate occurs as white crystals or a white crystalline powder. It has an acid taste at first, and a slight bitter taste later. It is freely soluble in water and in formic acid, and practi-cally insoluble in ethanol (99.5). It dissolves in 6 mol/L hydrochloric acid TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of L-Histidine Hydrochloride Hydrate as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. (2) A solution of L-Histidine Hydrochloride Hydrate (1 in 10) responds to Qualitative Tests <1.09> for chloride. D Optical rotation <2.49> [a]20: ＋9.2 – ＋10.69(5.5 g calcu-lated on the anhydrous basis, 6 mol/L hydrochloric acid TS, 50 mL, 100 mm). pH <2.54> The pH of a solution of 1.0 g of L-Histidine Hy-drochloride Hydrate in 10 mL of water is between 3.5 and 4.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution of 1.0 g of L-Histidine Hydrochloride Hydrate in 10 mL of water is clear and colorless. Sulfate <1.14>—Perform the test with 0.6 g of L-Histidine Hydrochloride Hydrate. Prepare the control so- <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatogra-phy, develop the plate with a mixture of 1-propanol and am-monia solution (28) (67:33) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly a solution of ninhydrin in a mixture of methanol and acetic acid (100) (97:3) (1 in 100) to the plate, and heat the plate at 809C for 10 minutes: the spot other than the principal spot obtained from the sample solution is not more intense than the spot from the standard solution. Water <2.48> 7.2 – 10.0z (0.12 g, volumetric titration, direct titration, using a mixture of methanol for water deter-mination and formamide for water determination (2:1) in-stead of methanol for water determination). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of L-Histidine Hydro-chloride Hydrate, dissolve in 3 mL of formic acid, add ex-actly 15 mL of 0.1 mol/L perchloric acid VS, and heat on a water bath for 30 minutes. After cooling, add 45 mL of acetic acid (100), and titrate <2.50> the excess of perchloric acid with 0.1 mol/L sodium acetate VS (potentiometric titra-tion). Perform a blank determination in the same manner. Each mL of 0.1 mol/L perchloric acid VS ＝ 9.581 mg of C6H9N3O2.HCl
storage conditions:
  en: Containers—Tight containers.

l-histidine
type: AminoAcidMonograph
pref label:
  en: L-Histidine
  ja: L-ヒスチジン
monograph id: JP18-l-histidine
publisher: JP
status: Official
version: 18
molecular formula: C6H9N3O2
molecular weight: 155.15
definition:
  en: L-Histidine contains not less than 99.
appearance:
  en: L-Histidine occurs as white, crystals or crystal-line powder, having a slight bitter taste. It is freely soluble in formic acid, and soluble in water, and practically insoluble in ethanol (99.5). It dissolves in 6 mol/L hydrochloric acid TS. It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Histidine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, dis-solve the sample with a little amount of water, evaporate the water at 609C under reduced pressure, dry the residue, and perform the test. D Optical rotation <2.49> [a]20: ＋11.8 – ＋12.89(5.5 g calcu-lated on the dried basis, 6 mol/L hydrochloric acid TS, 50 mL, 100 mm). pH <2.54> The pH of a solution of 1.0 g of L-Histidine in 50 mL of water is between 7.0 and 8.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution of 0.40 g of L-Histidine in 20 mL of water is clear and colorless. Chloride <1.03>—Perform the test with 0.5 g of L-Histidine. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Histidine. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Histidine. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Dissolve 1.0 g of L-Histidine in 30 mL of water by warming. To this solution add 2.4 mL of dilute hydrochloric acid, 2 mL of dilute acetic acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: To 1.0 mL of Standard Lead Solution add 2 mL of dilute acetic acid and water to make 50 mL (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of L-Histidine according to Method 1, and perform the test ac-cording to Method A. Prepare the control solution with 1.0 mL of Standard Iron Solution (not more than 10 ppm). Related substances—Dissolve 0.10 g of L-Histidine in 10 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make ex-actly 10 mL. Pipet 1 mL of this solution, add water to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography, develop the plate with a mixture of 1-propanol and ammonia solution (28) (67:33) to a dis-tance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly a solution of ninhydrin in a mixture of methanol and acetic acid (100) (97:3) (1 in 100) to the plate, and heat at 809C f…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of L-Histidine, dis-solve in 2 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (poten-tiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 15.52 mg of C6H9N3O2
storage conditions:
  en: Containers—Tight containers.

l-isoleucine
type: AminoAcidMonograph
pref label:
  en: L-Isoleucine
  ja: L-イソロイシン
monograph id: JP18-l-isoleucine
publisher: JP
status: Official
version: 18
molecular formula: C6H13NO2
molecular weight: 131.17
definition:
  en: L-Isoleucine, when dried, contains not less than 98.
appearance:
  en: L-Isoleucine occurs as white, crystals or crys-talline powder. It is odorless or has a faint characteristic odor, and has a slightly bitter taste. It is freely soluble in formic acid, sparingly soluble in water, and practically insoluble in ethanol (95). It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Isoleucine, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. D Optical rotation <2.49> [a]20: ＋39.5 – ＋41.59(after dry-ing, 1 g, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> Dissolve 1.0 g of L-Isoleucine in 100 mL of water: the pH of this solution is between 5.5 and 6.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of L-Isoleucine in 10 mL of 1 mol/L hydrochloric acid TS: the solution is clear and colorless. Chloride <1.03>—Perform the test with 0.5 g of L-Isoleucine. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Isoleucine. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Isoleucine. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Dissolve 1.0 g of L-Isoleucine in 40 mL of water and 2 mL of dilute acetic acid by warm- ing, cool, and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of Standard Lead Solution add 2 mL of dilute acetic acid and water to make 50 mL (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of L-Isoleucine according to Method 2, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of L-Isoleucine in 25 mL of water, and use this solution as the sample solu-tion. Pipet 1 mL of the sample solution, and add water to make exactly 50 mL. Pipet 5 mL of this solution, add water to make exactly 20 mL, and use this solution as the standard ‌JP XVIII Official Monographs / L-Isoleucine, L-Leucine and L-Valine Granules 1197 solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly the plate with a solution of ninhydrin in acetone (1 in 50), and heat the plate at 809C for 5 minutes: the spots other than t…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.13 g of L-Isoleucine, pre-viously dried, and dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS Flow rate: Adjust so that the retention time of L-valine is about 2.5 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, valine, isoleucine and leucine are eluted in this order, and the resolution between the peaks of isoleucine and leucine is not less than 1.5. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviations of the reten-tion time of isoleucine, leucine and valine are not more than 1.0z, respectively. Uniformity of dosage units <6.02> Perform the test accord-ing to the following method: the Granules in single-dose package meets the requirement of the Content uniformity test. To the total content of 1 package of L-Isoleucine, L-Leu-cine and L-Valine Granules add exactly V/25 mL of the in-ternal standard solution, and add 0.1 mol/L hydrochloric acid TS to make V mL so that each mL contains about 3.8 mg of L-isoleucine (C6H13NO2). To 2 mL of this solution add ＝ 13.12 mg of C6H 13NO2 0.02 mol/L hydrochloric acid TS to make 200 mL, and use this solution as the sample solution. Then, proceed as di-
storage conditions:
  en: Containers—Tight containers.

l-leucine
type: AminoAcidMonograph
pref label:
  en: L-Leucine
  ja: L-ロイシン
monograph id: JP18-l-leucine
publisher: JP
status: Official
version: 18
molecular formula: C6H13NO2
molecular weight: 131.17
definition:
  en: L-Leucine, when dried, contains not less than 98.
appearance:
  en: L-Leucine occurs as white, crystals or crystal-line powder. It is odorless or has a faint characteristic odor, and has a slightly bitter taste. It is freely soluble in formic acid, sparingly soluble in water, and practically insoluble in ethanol (95). It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Leucine, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋14.5 – ＋16.09(after dry-ing, 1 g, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> Dissolve 1.0 g of L-Leucine in 100 mL of water: Pipet 5 mL of this solution, add water to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solu-tion and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate, and heat the plate at 809C for 5 minutes: the spots other than the principal spot obtained from the sample solu-tion are not more intense than the spot from the standard so-lution. Loss on drying <2.41> Not more than 0.30z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.13 g of L-Leucine, previ-ously dried, and dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L per-chloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 13.12 mg of C6H13NO2
storage conditions:
  en: Containers—Well-closed contain-ers.

l-lysine-acetate
type: AminoAcidMonograph
pref label:
  en: L-Lysine Acetate
  ja: L-リシン酢酸塩
monograph id: JP18-l-lysine-acetate
publisher: JP
status: Official
version: 18
molecular formula: C6H14N2O2.C2H4O2
molecular weight: 206.24
definition:
  en: L-Lysine Acetate, when dried, contains not less than 98.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of L-Lysine Acetate as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. (2) A solution of L-Lysine Acetate (1 in 20) responds to Qualitative Tests <1.09> (2) for acetate. D Optical rotation <2.49> [a]20: ＋8.5 – ＋10.09(after drying, 2.5 g, water, 25 mL, 100 mm). pH <2.54> Dissolve 1.0 g of L-Lysine Acetate in 10 mL of water: the pH of the solution is between 6.5 and 7.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of L-Lysine Acetate in 10 mL of water: the solution is color-less and clear. Chloride <1.03>—Perform the test with 0.5 g of L-Lysine Acetate. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Lysine Acetate. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Lysine Acetate. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 1.0 g of L-Lysine Acetate according to Method 4, and perform the test. Pre- pare the control solution with 1.0 mL of Standard Lead So-lution (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of L-Lysine Acetate according to Method 1, and perform the test according to Method A. Prepare the control solution with 1.0 mL of Standard Iron Solution (not more than 10 ppm). Related substances—Weigh accurately about 0.5 g of L-Lysine Acetate, dissolve in 0.5 mL of hydrochloric acid and water to make exactly 100 mL. Pipet 10 mL of this solu-tion, add 0.02 mol/L hydrochloric acid to make exactly 50 mL, and use this solution as the sample solution. Separately, weigh accurately 2.5 mmol amounts of L-aspartic acid, L-threonine, L-serine, L-glutamic acid, glycine, L-alanine, L-cystine, L-valine, L-methionine, L-isoleucine, L-leucine, L-tyrosine, L-phenylalanine, L-lysine hydrochloride, ammo-nium chloride, L-histidine and L-arginine, dissolve in 0.1 mol/L hydrochloric acid TS to make exactly 1000 mL, and use this solution as the standard stock solution. Pipet 5 mL of this solution, add 0.02 mol/L hydrochloric acid to make exactly 100 mL. Pipet 4 mL of this solution, add 0.02 mol/L hydrochloric acid to make exactly 50 mL, and use this solu-tion as the standard solution. Perform the test with exactly 20 mL each of the sample s…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of L-Lysine Acetate, previously dried, dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L per-chloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 10.31 mg of C6H14N2O2.C2H4O2
storage conditions:
  en: Containers—Tight containers.

l-lysine-hydrochloride
type: AminoAcidMonograph
pref label:
  en: L-Lysine Hydrochloride
  ja: L-リシン塩酸塩
monograph id: JP18-l-lysine-hydrochloride
publisher: JP
status: Official
version: 18
definition:
  en: L-Lysine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: L-Lysine Hydrochloride occurs as a white pow-der. It has a slight, characteristic taste. It is freely soluble in water and in formic acid, and practi-cally insoluble in ethanol (95). It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of L-Lysine Hydrochloride, previously dried, as di-rected in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi-ties of absorption at the same wave numbers. If any differ-ence appears between the spectra, dissolve L-Lysine Hydro-chloride in water, evaporate the water to dryness at 609C, and repeat the test with the residue. (2) A solution of L-Lysine Hydrochloride (1 in 10) re-sponds to Qualitative Tests <1.09> for chloride. D Optical rotation <2.49> [a]20: ＋19.0 – ＋21.59(after dry-ing, 2 g, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> Dissolve 1.0 g of L-Lysine Hydrochloride in 10 mL of water: the pH of this solution is between 5.0 and 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of L-Lysine Hydrochloride in 10 mL of water: the solution is clear and colorless. Sulfate <1.14>—Perform the test with 0.6 g of L-Lysine Hydrochloride. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Lysine Hydrochloride. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 2.0 g of L-Lysine Hydrochloride according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of L-Lysine Hydrochloride according to Method 1, and per- ‌JP XVIII Official Monographs / Lysozyme Hydrochloride 1283 form the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of L-Lysine Hy-drochloride in 25 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 50 mL, pipet 5 mL of this solution, add water to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-propanol and ammonia water (28) (67:33) to a distance of about 10 cm, and dry the plate at 1009C for 30 minutes. Spray evenly the plate with a solution of ninhydrin in acetone (1 in 50) and heat the plate at 809C for 5 minutes: the spots other than the principal spot ob-tained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 1.0z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of L-Lysine Hydro-chloride, previously dried, dissolve in 2 mL of formic acid, add exactly 15 mL of 0.1 mol/L perchloric acid VS, and heat on a water bath for 30 minutes. After cooling, add 45 mL of acetic acid (100), and titrate <2.50> the excess perchloric acid with 0.1 mol/L sodium acetate VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 9.132 mg of C6H14N2O2.HCl
storage conditions:
  en: Containers—Tight containers.

l-methionine
type: AminoAcidMonograph
pref label:
  en: L-Methionine
  ja: ‌L-メチオニン
monograph id: JP18-l-methionine
publisher: JP
status: Official
version: 18
molecular formula: C5H11NO2S
molecular weight: 149.21
definition:
  en: L-Methionine, when dried, contains not less than 98.
appearance:
  en: L-Methionine occurs as white, crystals or crys-talline powder. It has a characteristic odor. It is freely soluble in formic acid, soluble in water, and very slightly soluble in ethanol (95). It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Methionine, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. D Optical rotation <2.49> [a]20: ＋21.0 – ＋25.09(after dry-ing, 0.5 g, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> Dissolve 0.5 g of L-Methionine in 20 mL of water: the pH of this solution is between 5.2 and 6.2.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of L-Methionine in 20 mL of water: the solution is clear and colorless. Chloride <1.03>—Dissolve 0.5 g of L-Methionine in 20 mL of water, and add 6 mL of dilute nitric acid and water to make 40 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS, 6 mL of dilute nitric acid and water to make 40 mL. In this test, to the test solution and the control solution add 10 mL each of silver nitrate TS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Methionine. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Methionine. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Dissolve 1.0 g of L-Methionine in 40 mL of water and 2 mL of dilute acetic acid, dissolve by warming, cool, and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the con-trol solution as follows: to 2.0 mL of Standard Lead Solu-tion add 2 mL of dilute acetic acid and water to make 50 mL (not more than 20 ppm). Arsenic <1.11>—Transfer 1.0 g of L-Methionine to a 100-mL decomposition flask, add 5 mL of nitric acid and 2 mL of sulfuric acid, put a small funnel on the mouth of the flask, and heat carefully until white fumes are evolved. After cooling, add two 2-mL portions of nitric acid, heat, add 2-mL portions of hydrogen peroxide (30) several times, and heat until the solution becomes colorless or pale yellow. After cooling, add 2 mL of saturated ammonium oxalate monohydrate solution, and heat again until white fumes are evolved. After cooling, add water to make 5 mL, and per-form the test with this solution as the test solution (not more than 2 ppm). Related substances—Dissolve 0.10 g of L-Methionine in 10 mL of water, and use this solution as the sampl…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of L-Methionine, pre-viously dried, and dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 14.92 mg of C5H11NO2S
storage conditions:
  en: Containers—Tight containers.

l-phenylalanine
type: AminoAcidMonograph
pref label:
  en: L-Phenylalanine
  ja: L-フェニルアラニン
monograph id: JP18-l-phenylalanine
publisher: JP
status: Official
version: 18
molecular formula: C9H11NO2
molecular weight: 165.19
definition:
  en: L-Phenylalanine, when dried, contains not less than 98.
appearance:
  en: L-Phenylalanine occurs as white, crystals or crystalline powder. It is odorless or has a faint characteristic odor, and has a slightly bitter taste. It is freely soluble in formic acid, sparingly soluble in water, and practically insoluble in ethanol (95). It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Phenylalanine, previously dried, as directed in the po-tassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －33.0 – －35.59(after dry-ing, 0.5 g, water, 25 mL, 100 mm). pH <2.54> Dissolve 0.20 g of L-Phenylalanine in 20 mL of water: the pH of this solution is between 5.3 and 6.3.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of L-Phenylalanine in 10 mL of 1 mol/L hydrochloric acid TS: the solution is clear and colorless. Chloride <1.03>—Perform the test with 0.5 g of L-Phenylalanine. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Phenylalanine. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Phenylalanine. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). ‌Heavy metals <1.07>—Dissolve 1.0 g of L-Phenylala-nine in 40 mL of water and 2 mL of dilute acetic acid by warming, cool, and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the con-trol solution as follows: to 2.0 mL of Standard Lead Solu-tion add 2 mL of dilute acetic acid and water to make 50 mL (not more than 20 ppm). Arsenic <1.11>—Dissolve 1.0 g of L-Phenylalanine in 5 mL of dilute hydrochloric acid and 15 mL of water, and perform the test with this solution as the test solution (not more than 2 ppm). Related substances—Dissolve 0.10 g of L-Phenylala-nine in 25 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add water to make exactly 50 mL. Pipet 5 mL of this solution, add water to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate, and heat the plate at 809C for 5 minutes: the spots other than the principa…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.17 g of L-Phenylalanine, previously dried, and dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 16.52 mg of C9H11NO2
storage conditions:
  en: Containers—Tight containers.

l-proline
type: AminoAcidMonograph
pref label:
  en: L-Proline
  ja: L-プロリン
monograph id: JP18-l-proline
publisher: JP
status: Official
version: 18
molecular formula: C5H9NO2
molecular weight: 115.13
definition:
  en: L-Proline contains not less than 99.
appearance:
  en: L-Proline occurs as white, crystals or crystal-line powder. It has a slightly sweet taste. It is very soluble in water and in formic acid, and slightly soluble in ethanol (99.5). It is deliquescent.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum 1 cm Absorbance <2.24> E1z 4 mg, methanol, 250 mL). (225 nm): 384 – 414 (after drying, of L-Proline as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Proglumide according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—To 1.0 g of Proglumide add 10 mL of a solution of magnesium nitrate hexahydrate in ethanol (95) (1 in 10) and 1.5 mL of hydrogen peroxide (30), burn the ethanol, and prepare the test solution according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of Proglumide in 5 mL of methanol, and use this solution as the sample so-lution. Pipet 1 mL of the sample solution, add methanol to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －84.0 – －86.09(1 g calculated on the dried basis, water, 25 mL, 100 mm). pH <2.54> The pH of a solution of 1.0 g of L-Proline in 10 mL of water is 5.9 to 6.9. Purity (1) Clarity and color of solution—Dissolve 1.0 g of L-Proline in 10 mL of water: the solution is clear and col-orless. Chloride <1.03>—Perform the test with 0.5 g of L-Proline. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Pro-line. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Proline. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 1.0 g of L-Pro-line according to Method 1, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of L-Proline according to Method 1, and perform the test ac-cording to Method A. Prepare the contr…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.12 g of L-Proline, dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 11.51 mg of C5H9NO2
storage conditions:
  en: Containers—Tight containers.

l-serine
type: AminoAcidMonograph
pref label:
  en: L-Serine
  ja: L-セリン
monograph id: JP18-l-serine
publisher: JP
status: Official
version: 18
molecular formula: C3H7NO3
molecular weight: 105.09
definition:
  en: L-Serine, when dried, contains not less than 98.
appearance:
  en: L-Serine occurs as white, crystals or a crystal-line powder. It has a slight sweet taste. It is freely soluble in water and in formic acid, and practi-cally insoluble in ethanol (99.5). It dissolves in 2 mol/L hydrochloric acid TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Serine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋14.0 – ＋16.09(After dry-ing, 2.5 g, 2 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> The pH of a solution prepared by dissolving 1.0 g of L-Serine in 10 mL of water is between 5.2 and 6.2. actly 10 mL. Pipet 1 mL of this solution, add water to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Then develop with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly a solution of ninhydrin in a mixture of methanol and acetic acid (100) (97:3) (1 in 100) on the plate, and heat the plate at 809C for 10 minutes: the spot other than the princi-pal spot obtained from the sample solution is not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.3z (1 g, 1059C, 3 hours). Residue on Ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.11 g of L-Serine, previ-ously dried, dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 10.51 mg of C3H7NO3
storage conditions:
  en: Containers—Tight containers.

l-threonine
type: AminoAcidMonograph
pref label:
  en: L-Threonine
  ja: L-トレオニン
monograph id: JP18-l-threonine
publisher: JP
status: Official
version: 18
molecular formula: C4H9NO3
molecular weight: 119.12
definition:
  en: L-Threonine, when dried, contains not less than 98.
appearance:
  en: L-Threonine occurs as white, crystals or crys-talline powder. It is odorless or has a slight, characteristic odor, and has a slightly sweet taste. It is freely soluble in formic acid, soluble in water, and practically insoluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Threonine, previously dried, as directed in the potas-sium bromide disk method under the Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －26.0 – －29.09(after dry-ing, 1.5 g, water, 25 mL, 100 mm). pH <2.54> Dissolve 0.20 g of L-Threonine in 20 mL of water: the pH of this solution is between 5.2 and 6.2.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of L-Threonine in 20 mL of water: the solution is clear and colorless. ‌Chloride <1.03>—Perform the test with 0.5 g of L-Threonine. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Threonine. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Threonine. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 1.0 g of L-Threo-nine according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Dissolve 1.0 g of L-Threonine in 5 mL of dilute hydrochloric acid, and perform the test with this solution as the test solution (not more than 2 ppm). Related substances—Dissolve 0.30 g of L-Threonine in 50 mL of water, and use this solution as the sample solu-tion. Pipet 1 mL of the sample solution, and add water to make exactly 50 mL. Pipet 5 mL of this solution, add water to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly the plate with a solution of ninhydrin in acetone (1 in 50), and heat the plate at 809C for 5 minutes: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.20z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.12 g of L-Threonine, pre-viously dried, dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 11.91 mg of C4H9NO3
storage conditions:
  en: Containers—Tight containers.

l-tryptophan
type: AminoAcidMonograph
pref label:
  en: L-Tryptophan
  ja: L-トリプトファン
monograph id: JP18-l-tryptophan
publisher: JP
status: Official
version: 18
molecular formula: C11H12N2O2
molecular weight: 204.23
definition:
  en: L-Tryptophan, when dried, contains not less than 98.
appearance:
  en: L-Tryptophan occurs as white to yellowish white, crystals or crystalline powder. It is odorless, and has a slightly bitter taste. It is freely soluble in formic acid, slightly soluble in water, and very slightly soluble in ethanol (95). It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Tryptophan, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. D Optical rotation <2.49> [a]20: －30.0 – －33.09Weigh accu- Amount (mg) of troxipide (C ＝ MS × QT/QS × 40 15H22N2O4) rately about 0.25 g of L-Tryptophan, previously dried, and dissolve in 20 mL of water by warming. After cooling, add water to make exactly 25 mL, and determine the optical rota- MS: Amount (mg) of Troxipide RS taken Internal standard solution—A solution of 4-aminoacetophe-none in 0.1 mol/L hydrochloric acid TS (3 in 2000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 258 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 309C. Mobile phase: To 1500 mL of diluted phosphoric acid (1 in 500) add diethylamine to adjust the pH to 3.0. To 1500 mL of this solution add 100 mL of methanol and 50 mL of tetrahydrofuran. Flow rate: Adjust so that the retention time of troxipide is about 7 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, troxipide and the internal standard are eluted in this order with the resolution between these peaks being not less than 3. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratio of the peak area of troxipide to that of the internal standard is not more than 1.0z.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity of solution—Dissolve 0.20 g of L-Tryp-tophan in 10 mL of 2 mol/L hydrochloric acid TS: the solu-tion is clear. Chloride <1.03>—Dissolve 0.5 g of L-Tryptophan in 6 mL of dilute nitric acid, and add water to make 50 mL. Per- form the test using this solution as the test solution. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochlo-ric acid VS (not more than 0.021z). Sulfate <1.14>—Dissolve 0.6 g of L-Tryptophan in 40 mL of water and 1 mL of dilute hydrochloric acid, and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Tryptophan. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 1.0 g of L-Tryp-tophan according to Method 4, and perform the test. Pre- pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 20 ppm). Arsenic <1.11>—Dissolve 1.0 g of L-Tryptophan in 3 mL of 1 mol/L hydrochloric acid TS and 2 mL of water by heating, and perform the test with this solution as the test so-lution (not more than 2 ppm). Related substances—Dissolve 0.30 g of L-Tryptophan in 1 mL of 1 mol/L hydrochloric acid TS, add water to make 50 mL, and use this solution as the sample solution. Pipet 1 ‌mL of the sample solution, and add water to make exactly 50 mL. Pipet 5 mL of this solution, add water to make exactly 20 mL, and use this solution as the standard solution. Per-form the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly a solution of ninhydrin in acetone (1 in 50) o…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of L-Tryptophan, pre-viously dried, dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 20.42 mg of C11H12N2O2
storage conditions:
  en: Containers—Tight containers.

l-tyrosine
type: AminoAcidMonograph
pref label:
  en: L-Tyrosine
  ja: L-チロシン
monograph id: JP18-l-tyrosine
publisher: JP
status: Official
version: 18
molecular formula: C9H11NO3
molecular weight: 181.19
definition:
  en: L-Tyrosine, when dried, contains not less than 99.
appearance:
  en: L-Tyrosine occurs as white, crystals or a crys-talline powder. It is freely soluble in formic acid, and practically insoluble in water and in ethanol (99.5). It dissolves in dilute hydrochloric acid and in ammonia TS. ‌Identification (1) Determine the absorption spectrum of a solution of L-Tyrosine in 0.1 mol/L hydrochloric acid (1 in 10,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-‌ acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS sorption at the same wavelengths. (2) Determine the infrared absorption spectrum of ＝ 18.12 mg of C9H 11NO3 L-Tyrosine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －10.5 – －12.59(after dry-ing, 2.5 g, 1 mol/L hydrochloric acid TS, 50 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of L-Tyrosine in 20 mL of 1 mol/L hydrochloric acid TS by warming: the solution is clear and colorless. Chloride <1.03>—Dissolve 0.5 g of L-Tyrosine in 12 mL of dilute nitric acid and 20 mL of water, and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: To 0.30 mL of 0.01 mol/L hydrochloric acid VS add 12 mL of dilute nitric acid and water to make 50 mL (not more than 0.021z). Sulfate <1.14>—Dissolve 0.6 g of L-Tyrosine in 5 mL of dilute hydrochloric acid, and add water to make 45 mL. Perform the test using this solution as the test solution. Pre-pare the control solution as follows: To 0.35 mL of 0.005 mol/L sulfuric acid VS add 5 mL of dilute hydrochloric acid and water to make 45 mL. To the test solution and the con-trol solution add 5 mL of barium chloride TS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Tyrosine. Prepare the control solution with 5.0 mL of Standard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 1.0 g of L-Tyro-sine according to Method 4, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of L-Tyrosine according to Method 3, and perform the test ac- cording to Method A. Prepare the control solution with 1.0 mL of Standard Iron Solution (not more than 10 ppm). Related substances—Dissolve 0.20 g of L-Tyrosine in 10 mL of diluted ammonia solution (28) (1 in 2), add water to make 20 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make ex-actly 10 mL, pipet 1 mL of this solution, add water to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.18 g of L-Tyrosine previ-ously dried, dissolve in 6 mL of formic acid, add 50 mL of
storage conditions:
  en: Containers—Tight containers.

l-valine
type: AminoAcidMonograph
pref label:
  en: L-Valine
  ja: L-バリン
monograph id: JP18-l-valine
publisher: JP
status: Official
version: 18
molecular formula: C5H11NO2
molecular weight: 117.15
definition:
  en: L-Valine, when dried, contains not less than 98.
appearance:
  en: L-Valine occurs as white, crystals or crystalline powder. It is odorless or has a faint characteristic odor, and has a slightly sweet taste, which becomes bitter. It is freely soluble in formic acid, soluble in water, and practically insoluble in ethanol (95). It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of L-Valine, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋26.5 – ＋29.09(after dry-ing, 2 g, 6 mol/L hydrochloric acid TS, 25 mL, 100 mm). pH <2.54> Dissolve 0.5 g of L-Valine in 20 mL of water: the pH of this solution is between 5.5 and 6.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of L-Valine in 20 mL of water: the solution is clear and col-orless. Chloride <1.03>—Perform the test with 0.5 g of L-Valine. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.6 g of L-Valine. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.028z). Ammonium <1.02>—Perform the test with 0.25 g of L-Valine. Prepare the control solution with 5.0 mL of Stand-ard Ammonium Solution (not more than 0.02z). Heavy metals <1.07>—Proceed with 1.0 g of L-Valine according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Proceed with 1.0 g of L-Valine, pre-pare the test solution according to Method 2, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of L-Valine in 25 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add water to make exactly 50 mL. Pipet 5 mL of this solution, add water to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and dry the plate at 809C for 30 minutes. Spray evenly a solution of ninhydrin in acetone (1 in 50) on the plate, and heat the plate at 809C for 5 minutes: the spots other than the principal spot obtained from the ‌sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.30z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.12 g of L-Valine, previ-ously dried, and dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L per-chloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 11.72 mg of C5H11NO2
storage conditions:
  en: Containers—Tight containers.

achyranthes-root-achyranthes-bidentata-blume-or
type: BiologicalSource
organism name: Achyranthes bidentata Blume or
derived from organism: achyranthes-bidentata-blume-or
organism part: the root

agar-gelidium-elegans-kuetzing
type: BiologicalSource
organism name: Gelidium elegans Kuetzing
derived from organism: gelidium-elegans-kuetzing

akebia-stem-akebia-quinata-decaisne-or
type: BiologicalSource
organism name: Akebia quinata Decaisne or
derived from organism: akebia-quinata-decaisne-or
organism part: climbing stem

akebia-stem-akebia-quinata-decaisne
type: BiologicalSource
organism name: Akebia quinata Decaisne
derived from organism: akebia-quinata-decaisne
organism part: climbing stem
family: Lardizabalaceae

alisma-tuber-alisma-orientale-juzepczuk
type: BiologicalSource
organism name: Alisma orientale Juzepczuk
derived from organism: alisma-orientale-juzepczuk
organism part: tuber
family: Alismataceae

aloe-the-leaves-mainly-of
type: BiologicalSource
organism name: the leaves mainly of
derived from organism: the-leaves-mainly-of
organism part: dried juice

aloe-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 5 mL

aloe-aloe-ferox-miller
type: BiologicalSource
organism name: Aloe ferox Miller
derived from organism: aloe-ferox-miller
organism part: dried juice

alpinia-officinarum-rhizome-alpinia-officinarum-hance
type: BiologicalSource
organism name: Alpinia officinarum Hance
derived from organism: alpinia-officinarum-hance
organism part: rhizome
family: Zingiberaceae

amomum-seed-amomum-villosum-loureiro-var
type: BiologicalSource
organism name: Amomum villosum Loureiro var
derived from organism: amomum-villosum-loureiro-var
organism part: seed mass

anemarrhena-rhizome-anemarrhena-asphodeloides-bunge
type: BiologicalSource
organism name: Anemarrhena asphodeloides Bunge
derived from organism: anemarrhena-asphodeloides-bunge
organism part: rhizome
family: Liliaceae

angelica-dahurica-root-angelica-dahurica-bentham-et
type: BiologicalSource
organism name: Angelica dahurica Bentham et
derived from organism: angelica-dahurica-bentham-et
organism part: the root

apricot-kernel-prunus-armeniaca-linn
type: BiologicalSource
organism name: Prunus armeniaca Linn
derived from organism: prunus-armeniaca-linn
organism part: the seed

aralia-rhizome-aralia-cordata-thunberg
type: BiologicalSource
organism name: Aralia cordata Thunberg
derived from organism: aralia-cordata-thunberg
organism part: usually the rhizome
family: Araliaceae

areca-areca-catechu-linn
type: BiologicalSource
organism name: Areca catechu Linn
derived from organism: areca-catechu-linn
organism part: the seed

artemisia-capillaris-flower-artemisia-capillaris-thunberg
type: BiologicalSource
organism name: Artemisia capillaris Thunberg
derived from organism: artemisia-capillaris-thunberg
organism part: Flower is the capitulum
family: Compositae

artemisia-leaf-artemisia-princeps-pampanini-or
type: BiologicalSource
organism name: Artemisia princeps Pampanini or
derived from organism: artemisia-princeps-pampanini-or
organism part: leaf and twig

artemisia-leaf-artemisia-princeps-pampanini
type: BiologicalSource
organism name: Artemisia princeps Pampanini
derived from organism: artemisia-princeps-pampanini
organism part: leaf and twig
family: Compositae

asiasarum-root-asiasarum-heterotropoides-f
type: BiologicalSource
organism name: Asiasarum heterotropoides F
derived from organism: asiasarum-heterotropoides-f
organism part: root and rhizome

asparagus-root-asparagus-cochinchinensis-merrill
type: BiologicalSource
organism name: Asparagus cochinchinensis Merrill
derived from organism: asparagus-cochinchinensis-merrill
organism part: the root
family: Liliaceae

astragalus-root-astragalus-membranaceus-bunge-or
type: BiologicalSource
organism name: Astragalus membranaceus Bunge or
derived from organism: astragalus-membranaceus-bunge-or
organism part: the root

astragalus-root-astragalus-membranaceus-bunge
type: BiologicalSource
organism name: Astragalus membranaceus Bunge
derived from organism: astragalus-membranaceus-bunge
organism part: the root
family: Leguminosae

atractylodes-lancea-rhizome-atractylodes-lancea-de-candolle
type: BiologicalSource
organism name: Atractylodes lancea De Candolle
derived from organism: atractylodes-lancea-de-candolle
organism part: rhizome

atractylodes-rhizome-light-yellow
type: BiologicalSource
organism name: light yellow
derived from organism: light-yellow
substance type: fibrous. A transverse section, with fine dots

bear-bile-ursus-arctos-linn
type: BiologicalSource
organism name: Ursus arctos Linn
derived from organism: ursus-arctos-linn
substance type: dried bile

bearberry-leaf-arctostaphylos-uvaursi-sprengel
type: BiologicalSource
organism name: Arctostaphylos uvaursi Sprengel
derived from organism: arctostaphylos-uvaursi-sprengel
organism part: the leaf
family: Ericaceae

bearberry-leaf-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

yellow-beeswax-apis-mellifera-linn
type: BiologicalSource
organism name: Apis mellifera Linn
derived from organism: apis-mellifera-linn
substance type: honeycombs such as those

belladonna-root-atropa-belladonna-linn
type: BiologicalSource
organism name: Atropa belladonna Linn
derived from organism: atropa-belladonna-linn
organism part: the root

belladonna-root-diethyl-ether
type: BiologicalSource
organism name: diethyl ether
derived from organism: diethyl-ether
substance type: add 25 mL

belladonna-total-alkaloids-the-extract-from-belladonna
type: BiologicalSource
organism name: the extract from Belladonna
derived from organism: the-extract-from-belladonna
substance type: prepared by purification

belladonna-total-alkaloids-the-internal-standard-solution
type: BiologicalSource
organism name: the internal standard solution
derived from organism: the-internal-standard-solution
substance type: solution, add exactly 3 mL

benincasa-seed-slightly-sclerified-parenchyma-beneath
type: BiologicalSource
organism name: slightly sclerified parenchyma beneath
derived from organism: slightly-sclerified-parenchyma-beneath
substance type: composed

bitter-cardamon-alpinia-oxyphylla-miquel
type: BiologicalSource
organism name: Alpinia oxyphylla Miquel
derived from organism: alpinia-oxyphylla-miquel
organism part: fruit
family: Zingiberaceae

bitter-orange-peel-the-ripe-fruit-of
type: BiologicalSource
organism name: the ripe fruit of
derived from organism: the-ripe-fruit-of
substance type: pericarp

brown-rice-oryza-sativa-linn
type: BiologicalSource
organism name: Oryza sativa Linn
derived from organism: oryza-sativa-linn
organism part: fruit

bupleurum-root-bupleurum-falcatum-linn
type: BiologicalSource
organism name: Bupleurum falcatum Linn
derived from organism: bupleurum-falcatum-linn
organism part: the root

bupleurum-root-dilute-sodium-hydroxide-ts
type: BiologicalSource
organism name: dilute sodium hydroxide TS
derived from organism: dilute-sodium-hydroxide-ts
substance type: solution, add 2.5 mL

burdock-fruit-arctium-lappa-linn
type: BiologicalSource
organism name: Arctium lappa Linn
derived from organism: arctium-lappa-linn
organism part: fruit

cacao-butter-theobroma-cacao-linn
type: BiologicalSource
organism name: Theobroma cacao Linn
derived from organism: theobroma-cacao-linn
organism part: fat obtained from the seed

calumba-jateorhiza-columba-miers
type: BiologicalSource
organism name: Jateorhiza columba Miers
derived from organism: jateorhiza-columba-miers
organism part: cross-sectioned root
family: Menispermaceae

capsicum-capsicum-annuum-linn
type: BiologicalSource
organism name: Capsicum annuum Linn
derived from organism: capsicum-annuum-linn
organism part: fruit

cardamon-elettaria-cardamomum-maton
type: BiologicalSource
organism name: Elettaria cardamomum Maton
derived from organism: elettaria-cardamomum-maton
organism part: fruit
family: Zingiberaceae

cassia-seed-cassia-obtusifolia-linn
type: BiologicalSource
organism name: Cassia obtusifolia Linn
derived from organism: cassia-obtusifolia-linn
organism part: the seed

catalpa-fruit-catalpa-ovata-g
type: BiologicalSource
organism name: Catalpa ovata G
derived from organism: catalpa-ovata-g
organism part: fruit

cherry-bark-prunus-jamasakura-siebold-ex
type: BiologicalSource
organism name: Prunus jamasakura Siebold ex
derived from organism: prunus-jamasakura-siebold-ex
organism part: the bark

cimicifuga-rhizome-cimicifuga-dahurica-maximowicz
type: BiologicalSource
organism name: Cimicifuga dahurica Maximowicz
derived from organism: cimicifuga-dahurica-maximowicz
organism part: rhizome

cinnamon-bark-cinnamomum-cassia-j
type: BiologicalSource
organism name: Cinnamomum cassia J
derived from organism: cinnamomum-cassia-j
organism part: bark of the trunk

citrus-unshiu-peel-the-ripe-fruit-of
type: BiologicalSource
organism name: the ripe fruit of
derived from organism: the-ripe-fruit-of
substance type: pericarp

citrus-unshiu-peel-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

citrus-unshiu-peel-citrus-unshiu-marcowicz
type: BiologicalSource
organism name: Citrus unshiu Marcowicz
derived from organism: citrus-unshiu-marcowicz
organism part: pericarp of the ripe fruit
family: Rutaceae

clematis-root-clematis-mandshurica-ruprecht
type: BiologicalSource
organism name: Clematis mandshurica Ruprecht
derived from organism: clematis-mandshurica-ruprecht
organism part: Root is the root with rhizome

clematis-root-short-rhizome-and-numerous
type: BiologicalSource
organism name: short rhizome and numerous
derived from organism: short-rhizome-and-numerous
organism part: Root consists

clematis-root-acetic-anhydride
type: BiologicalSource
organism name: acetic anhydride
derived from organism: acetic-anhydride
organism part: Root add 3 mL

clove-syzygium-aromaticum-merrill-et
type: BiologicalSource
organism name: Syzygium aromaticum Merrill et
derived from organism: syzygium-aromaticum-merrill-et
organism part: flowering bud

cnidium-monnieri-fruit-cnidium-monnieri-cusson
type: BiologicalSource
organism name: Cnidium monnieri Cusson
derived from organism: cnidium-monnieri-cusson
organism part: fruit
family: Umbelliferae

cnidium-rhizome-cnidium-officinale-makino
type: BiologicalSource
organism name: Cnidium officinale Makino
derived from organism: cnidium-officinale-makino
organism part: rhizome
family: Umbelliferae

codonopsis-root-codonopsis-pilosula-nannfeldt-or
type: BiologicalSource
organism name: Codonopsis pilosula Nannfeldt or
derived from organism: codonopsis-pilosula-nannfeldt-or
organism part: Root is the root

codonopsis-root-codonopsis-pilosula-nannfeldt
type: BiologicalSource
organism name: Codonopsis pilosula Nannfeldt
derived from organism: codonopsis-pilosula-nannfeldt
organism part: Root is the root
family: Campanulaceae

coix-seed-coix-lachryma
type: BiologicalSource
organism name: Coix lachryma
derived from organism: coix-lachryma
organism part: the seed

condurango-marsdenia-cundurango-reichenbach-filius
type: BiologicalSource
organism name: Marsdenia cundurango Reichenbach filius
derived from organism: marsdenia-cundurango-reichenbach-filius
organism part: bark of the trunk
family: Asclepiadaceae

coptis-rhizome-the-standard-solution
type: BiologicalSource
organism name: the standard solution
derived from organism: the-standard-solution
substance type: not more than that
family: not more than 5 ppm

coptis-rhizome-coptis-japonica-makino
type: BiologicalSource
organism name: Coptis japonica Makino
derived from organism: coptis-japonica-makino
organism part: Rhizome is the rhizome

coptis-rhizome-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 20 mL

cornus-fruit-cornus-officinalis-siebold-et
type: BiologicalSource
organism name: Cornus officinalis Siebold et
derived from organism: cornus-officinalis-siebold-et
substance type: pulp of the pseudocarp

cornus-fruit-the-spot
type: BiologicalSource
organism name: the spot
derived from organism: the-spot
substance type: found immediately below

corydalis-tuber-corydalis-turtschaninovii-basser-forma
type: BiologicalSource
organism name: Corydalis turtschaninovii Basser forma
derived from organism: corydalis-turtschaninovii-basser-forma
organism part: Tuber is the tuber

corydalis-tuber-sodium-perchlorate
type: BiologicalSource
organism name: sodium perchlorate
derived from organism: sodium-perchlorate
substance type: solution add 14.05 g

corydalis-tuber-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 5 mL

crataegus-fruit-parenchyma-cells-beneath-these
type: BiologicalSource
organism name: parenchyma cells beneath these
derived from organism: parenchyma-cells-beneath-these
substance type: or 2- to 3-cellular layer

cyperus-rhizome-cyperus-rotundus-linn
type: BiologicalSource
organism name: Cyperus rotundus Linn
derived from organism: cyperus-rotundus-linn
organism part: rhizome

digenea-digenea-simplex-c
type: BiologicalSource
organism name: Digenea simplex C
derived from organism: digenea-simplex-c
organism part: whole algae

dioscorea-rhizome-dioscorea-japonica-thunberg-or
type: BiologicalSource
organism name: Dioscorea japonica Thunberg or
derived from organism: dioscorea-japonica-thunberg-or
organism part: rhizome (rhizophore)

dioscorea-rhizome-dioscorea-japonica-thunberg
type: BiologicalSource
organism name: Dioscorea japonica Thunberg
derived from organism: dioscorea-japonica-thunberg
organism part: rhizome (rhizophore)
family: Dioscoreaceae

dolichos-seed-dolichos-lablab-linn
type: BiologicalSource
organism name: Dolichos lablab Linn
derived from organism: dolichos-lablab-linn
organism part: the seed

dolichos-seed-sclerenchymatous-and-sandglass-like
type: BiologicalSource
organism name: sclerenchymatous and sandglass like
derived from organism: sclerenchymatous-and-sandglass-like
substance type: a single layer

eleutherococcus-senticosus-rhizome-eleutherococcus-senticosus-maximowicz
type: BiologicalSource
organism name: Eleutherococcus senticosus Maximowicz
derived from organism: eleutherococcus-senticosus-maximowicz
organism part: rhizome
family: Acanthopanax senticosus Harms

ephedra-herb-ephedra-sinica-stapf
type: BiologicalSource
organism name: Ephedra sinica Stapf
derived from organism: ephedra-sinica-stapf
organism part: terrestrial stem

ephedra-herb-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

epimedium-herb-epimedium-koreanum-nakai
type: BiologicalSource
organism name: Epimedium koreanum Nakai
derived from organism: epimedium-koreanum-nakai
substance type: terrestrial part

eucommia-bark-eucommia-ulmoides-oliver
type: BiologicalSource
organism name: Eucommia ulmoides Oliver
derived from organism: eucommia-ulmoides-oliver
organism part: the bark
family: Eucommiaceae

euodia-fruit-euodia-officinalis-dode
type: BiologicalSource
organism name: Euodia officinalis Dode
derived from organism: euodia-officinalis-dode
organism part: fruit
family: Evodia officinalis Dode

fennel-foeniculum-vulgare-miller
type: BiologicalSource
organism name: Foeniculum vulgare Miller
derived from organism: foeniculum-vulgare-miller
organism part: fruit
family: Umbelliferae

forsythia-fruit-forsythia-suspensa-vahl
type: BiologicalSource
organism name: Forsythia suspensa Vahl
derived from organism: forsythia-suspensa-vahl
organism part: fruit
family: Oleaceae

fritillaria-bulb-fritillaria-verticillata-willdenow-var
type: BiologicalSource
organism name: Fritillaria verticillata Willdenow var
derived from organism: fritillaria-verticillata-willdenow-var
substance type: the bulb

gambir-the-leaves-and-young
type: BiologicalSource
organism name: the leaves and young
derived from organism: the-leaves-and-young

gardenia-fruit-gardenia-jasminoides-ellis
type: BiologicalSource
organism name: Gardenia jasminoides Ellis
derived from organism: gardenia-jasminoides-ellis
organism part: fruit
family: Rubiaceae

gardenia-fruit-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

gastrodia-tuber-gastrodia-elata-blume
type: BiologicalSource
organism name: Gastrodia elata Blume
derived from organism: gastrodia-elata-blume
organism part: tuber
family: Orchidaceae

gentian-gentiana-lutea-linn
type: BiologicalSource
organism name: Gentiana lutea Linn
derived from organism: gentiana-lutea-linn
organism part: root and rhizome

geranium-herb-geranium-thunbergii-siebold-et
type: BiologicalSource
organism name: Geranium thunbergii Siebold et
derived from organism: geranium-thunbergii-siebold-et
substance type: terrestrial part

ginseng-panax-ginseng-c
type: BiologicalSource
organism name: Panax ginseng C
derived from organism: panax-ginseng-c
organism part: the root

ginseng-dilute-sodium-hydroxide-ts
type: BiologicalSource
organism name: dilute sodium hydroxide TS
derived from organism: dilute-sodium-hydroxide-ts
substance type: solution, add 3 mL

ginseng-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

glehnia-root-and-rhizome-glehnia-littoralis-fr
type: BiologicalSource
organism name: Glehnia littoralis Fr
derived from organism: glehnia-littoralis-fr
organism part: root and rhizome

glycyrrhiza-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

hedysarum-root-hedysarum-polybotrys-handel
type: BiologicalSource
organism name: Hedysarum polybotrys Handel
derived from organism: hedysarum-polybotrys-handel
organism part: the root

hemp-fruit-cannabis-sativa-linn
type: BiologicalSource
organism name: Cannabis sativa Linn
derived from organism: cannabis-sativa-linn
organism part: fruit

honey-apis-mellifera-linn
type: BiologicalSource
organism name: Apis mellifera Linn
derived from organism: apis-mellifera-linn
substance type: honeycomb

houttuynia-herb-houttuynia-cordata-thunberg
type: BiologicalSource
organism name: Houttuynia cordata Thunberg
derived from organism: houttuynia-cordata-thunberg
substance type: terrestrial part
family: Saururaceae

imperata-rhizome-imperata-cylindrica-beauvois
type: BiologicalSource
organism name: Imperata cylindrica Beauvois
derived from organism: imperata-cylindrica-beauvois
organism part: rhizome
family: Gramineae

imperata-rhizome-sulfuric-acid-to-make
type: BiologicalSource
organism name: sulfuric acid to make
derived from organism: sulfuric-acid-to-make
substance type: solution in a test tube, and add carefully 0.5 mL

ipecac-cephaelis-ipecacuanha-a
type: BiologicalSource
organism name: Cephaelis ipecacuanha A
derived from organism: cephaelis-ipecacuanha-a
organism part: root and rhizome

ipecac-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

ipecac-syrup-glycerin-and-simple-syrup
type: BiologicalSource
organism name: Glycerin and Simple Syrup
derived from organism: glycerin-and-simple-syrup
substance type: solution add 100 mL

ipecac-syrup-the-standard-solution-under
type: BiologicalSource
organism name: the standard solution under
derived from organism: the-standard-solution-under
substance type: run with 2 mL

japanese-angelica-root-angelica-acutiloba-kitagawa-or
type: BiologicalSource
organism name: Angelica acutiloba Kitagawa or
derived from organism: angelica-acutiloba-kitagawa-or
organism part: the root

japanese-gentian-gentiana-scabra-bunge
type: BiologicalSource
organism name: Gentiana scabra Bunge
derived from organism: gentiana-scabra-bunge
organism part: root and rhizome

japanese-gentian-characteristic-cells-divided-into
type: BiologicalSource
organism name: characteristic cells divided into
derived from organism: characteristic-cells-divided-into
substance type: consisting

japanese-valerian-valeriana-fauriei-briquet
type: BiologicalSource
organism name: Valeriana fauriei Briquet
derived from organism: valeriana-fauriei-briquet
organism part: root and rhizome
family: Valerianaceae

japanese-zanthoxylum-peel-the-ripe-fruit-of
type: BiologicalSource
organism name: the ripe fruit of
derived from organism: the-ripe-fruit-of
substance type: pericarps

jujube-ziziphus-jujuba-miller-var
type: BiologicalSource
organism name: Ziziphus jujuba Miller var
derived from organism: ziziphus-jujuba-miller-var
organism part: fruit

jujube-seed-ziziphus-jujuba-miller-var
type: BiologicalSource
organism name: Ziziphus jujuba Miller var
derived from organism: ziziphus-jujuba-miller-var
organism part: the seed

koi-the-starch-of-zea
type: BiologicalSource
organism name: the starch of Zea
derived from organism: the-starch-of-zea
substance type: a saccharized substance obtained by hydrolysis

purified-lanolin-the-fatlike-substance-obtained
type: BiologicalSource
organism name: the fatlike substance obtained
derived from organism: the-fatlike-substance-obtained
substance type: purified product

purified-lanolin-the-spot-of-standard
type: BiologicalSource
organism name: the spot of standard
derived from organism: the-spot-of-standard
substance type: observable same level

purified-lanolin-ovis-aries-linn
type: BiologicalSource
organism name: Ovis aries Linn
derived from organism: ovis-aries-linn
substance type: the wool

leonurus-herb-leonurus-japonicus-houttuyn-or
type: BiologicalSource
organism name: Leonurus japonicus Houttuyn or
derived from organism: leonurus-japonicus-houttuyn-or
organism part: aerial part

lilium-bulb-lilium-lancifolium-thunberg
type: BiologicalSource
organism name: Lilium lancifolium Thunberg
derived from organism: lilium-lancifolium-thunberg
organism part: scaly leaves

lindera-root-lindera-strychnifolia-fernandez
type: BiologicalSource
organism name: Lindera strychnifolia Fernandez
derived from organism: lindera-strychnifolia-fernandez
organism part: the root

lithospermum-root-lithospermum-erythrorhizon-siebold-et
type: BiologicalSource
organism name: Lithospermum erythrorhizon Siebold et
derived from organism: lithospermum-erythrorhizon-siebold-et
organism part: the root

longan-aril-euphoria-longana-lamarck
type: BiologicalSource
organism name: Euphoria longana Lamarck
derived from organism: euphoria-longana-lamarck
substance type: the aril
family: Sapindaceae

longan-aril-depressed-parenchyma-cells
type: BiologicalSource
organism name: depressed parenchyma cells
derived from organism: depressed-parenchyma-cells
substance type: observed parenchyma consisting

longgu-large-mammal
type: BiologicalSource
organism name: large mammal
derived from organism: large-mammal
substance type: ossified bone

lonicera-leaf-and-stem-lonicera-japonica-thunberg
type: BiologicalSource
organism name: Lonicera japonica Thunberg
derived from organism: lonicera-japonica-thunberg
organism part: leaves and stems
family: Caprifoliaceae

loquat-leaf-eriobotrya-japonica-lindley
type: BiologicalSource
organism name: Eriobotrya japonica Lindley
derived from organism: eriobotrya-japonica-lindley
organism part: the leaf
family: Rosaceae

lycium-bark-lycium-chinense-miller-or
type: BiologicalSource
organism name: Lycium chinense Miller or
derived from organism: lycium-chinense-miller-or
organism part: root bark

lycium-fruit-lycium-chinense-miller-or
type: BiologicalSource
organism name: Lycium chinense Miller or
derived from organism: lycium-chinense-miller-or
organism part: fruit

magnolia-bark-magnolia-obovata-thunberg
type: BiologicalSource
organism name: Magnolia obovata Thunberg
derived from organism: magnolia-obovata-thunberg
organism part: bark of the trunk

magnolia-bark-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

magnolia-flower-magnolia-biondii-pampanini
type: BiologicalSource
organism name: Magnolia biondii Pampanini
derived from organism: magnolia-biondii-pampanini
organism part: flower bud

mallotus-bark-mallotus-japonica-m
type: BiologicalSource
organism name: Mallotus japonica M
derived from organism: mallotus-japonica-m
organism part: the bark

malt-hordeum-vulgare-linn
type: BiologicalSource
organism name: Hordeum vulgare Linn
derived from organism: hordeum-vulgare-linn
substance type: dried ripe caryopsis

mentha-herb-mentha-arvensis-linn
type: BiologicalSource
organism name: Mentha arvensis Linn
derived from organism: mentha-arvensis-linn
substance type: terrestrial part

mentha-water-mentha-oil
type: BiologicalSource
organism name: mentha oil
derived from organism: mentha-oil
substance type: a clear, colorless liquid, having the odor

moutan-bark-paeonia-suffruticosa-andrews
type: BiologicalSource
organism name: Paeonia suffruticosa Andrews
derived from organism: paeonia-suffruticosa-andrews
organism part: root bark
family: Paeonia moutan Sims

mulberry-bark-morus-alba-linn
type: BiologicalSource
organism name: Morus alba Linn
derived from organism: morus-alba-linn
organism part: root bark

nelumbo-seed-nelumbo-nucifera-gaertner
type: BiologicalSource
organism name: Nelumbo nucifera Gaertner
derived from organism: nelumbo-nucifera-gaertner
organism part: the seed
family: Nymphaeaceae

nelumbo-seed-compressed-cells
type: BiologicalSource
organism name: compressed cells
derived from organism: compressed-cells
substance type: and parenchyma

nelumbo-seed-calcium-oxalate-and-tannin
type: BiologicalSource
organism name: calcium oxalate and tannin
derived from organism: calcium-oxalate-and-tannin
substance type: and parenchyma; aggregate crystals

notopterygium-notopterygium-incisum-ting-ex
type: BiologicalSource
organism name: Notopterygium incisum Ting ex
derived from organism: notopterygium-incisum-ting-ex
organism part: rhizome and root

nuphar-rhizome-nuphar-japonica-de-candolle
type: BiologicalSource
organism name: Nuphar japonica De Candolle
derived from organism: nuphar-japonica-de-candolle
organism part: longitudinally split rhizome

nutmeg-myristica-fragrans-houttuyn
type: BiologicalSource
organism name: Myristica fragrans Houttuyn
derived from organism: myristica-fragrans-houttuyn
organism part: the seed
family: Myristicaceae

nux-vomica-strychnos-nux
type: BiologicalSource
organism name: Strychnos nux
derived from organism: strychnos-nux
organism part: the seed

nux-vomica-diethyl-ether
type: BiologicalSource
organism name: diethyl ether
derived from organism: diethyl-ether
substance type: solution add 20 mL

nux-vomica-the-internal-standard-solution
type: BiologicalSource
organism name: the internal standard solution
derived from organism: the-internal-standard-solution
substance type: solution, add exactly 10 mL

nux-vomica-the-standard-solution-under
type: BiologicalSource
organism name: the standard solution under
derived from organism: the-standard-solution-under
substance type: run with 5 mL

ophiopogon-root-the-root-of-ophiopogon
type: BiologicalSource
organism name: the root of Ophiopogon
derived from organism: the-root-of-ophiopogon
substance type: enlarged part

oriental-bezoar-bos-taurus-linn
type: BiologicalSource
organism name: Bos taurus Linn
derived from organism: bos-taurus-linn
substance type: a stone formed in the gall sac

oyster-shell-ostrea-gigas-thunberg
type: BiologicalSource
organism name: Ostrea gigas Thunberg
derived from organism: ostrea-gigas-thunberg
substance type: shell
family: Ostreidae

panax-japonicus-rhizome-panax-japonicus-c
type: BiologicalSource
organism name: Panax japonicus C
derived from organism: panax-japonicus-c
organism part: rhizome

peach-kernel-prunus-persica-batsch-or
type: BiologicalSource
organism name: Prunus persica Batsch or
derived from organism: prunus-persica-batsch-or
organism part: the seed

peony-root-paeonia-lactiflora-pallas
type: BiologicalSource
organism name: Paeonia lactiflora Pallas
derived from organism: paeonia-lactiflora-pallas
organism part: the root
family: Paeoniaceae

peony-root-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

perilla-herb-branches-of-perilla-frutescens
type: BiologicalSource
organism name: branches of Perilla frutescens
derived from organism: branches-of-perilla-frutescens
organism part: leaves and the tips

pharbitis-seed-pharbitis-nil-choisy
type: BiologicalSource
organism name: Pharbitis nil Choisy
derived from organism: pharbitis-nil-choisy
organism part: Seed is the seed
family: Convolvulaceae

phellodendron-bark-phellodendron-amurense-ruprecht-or
type: BiologicalSource
organism name: Phellodendron amurense Ruprecht or
derived from organism: phellodendron-amurense-ruprecht-or
organism part: the bark

phellodendron-bark-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 20 mL

phellodendron-bark-phellodendron-amurense-ruprecht
type: BiologicalSource
organism name: Phellodendron amurense Ruprecht
derived from organism: phellodendron-amurense-ruprecht
organism part: the bark
family: Rutaceae

picrasma-wood-picrasma-quassioides-bennet
type: BiologicalSource
organism name: Picrasma quassioides Bennet
derived from organism: picrasma-quassioides-bennet
organism part: the wood
family: Simaroubaceae

pinellia-tuber-pinellia-ternata-breitenbach
type: BiologicalSource
organism name: Pinellia ternata Breitenbach
derived from organism: pinellia-ternata-breitenbach
organism part: tuber
family: Araceae

plantago-herb-plantago-asiatica-linn
type: BiologicalSource
organism name: Plantago asiatica Linn
derived from organism: plantago-asiatica-linn
substance type: entire plant

plantago-seed-plantago-asiatica-linn
type: BiologicalSource
organism name: Plantago asiatica Linn
derived from organism: plantago-asiatica-linn
organism part: the seed

plantago-seed-cells-containing-mucilage
type: BiologicalSource
organism name: cells containing mucilage
derived from organism: cells-containing-mucilage
substance type: composed

platycodon-root-platycodon-grandiflorus-a
type: BiologicalSource
organism name: Platycodon grandiflorus A
derived from organism: platycodon-grandiflorus-a
organism part: the root

pogostemi-herb-pogostemon-cablin-bentham
type: BiologicalSource
organism name: Pogostemon cablin Bentham
derived from organism: pogostemon-cablin-bentham
substance type: terrestrial part
family: Labiatae

polygala-root-polygala-tenuifolia-willdenow
type: BiologicalSource
organism name: Polygala tenuifolia Willdenow
derived from organism: polygala-tenuifolia-willdenow
organism part: root or the root bark
family: Polygalaceae

polygonatum-rhizome-polygonatum-kingianum-collett-et
type: BiologicalSource
organism name: Polygonatum kingianum Collett et
derived from organism: polygonatum-kingianum-collett-et
organism part: rhizome

polygonatum-rhizome-epidermis-parenchyma-lie
type: BiologicalSource
organism name: epidermis parenchyma lie
derived from organism: epidermis-parenchyma-lie
substance type: coated with cuticle; inside

polygonum-root-polygonum-multiflorum-thunberg
type: BiologicalSource
organism name: Polygonum multiflorum Thunberg
derived from organism: polygonum-multiflorum-thunberg
organism part: the root
family: Polygonaceae

polyporus-sclerotium-polyporus-umbellatus-fries
type: BiologicalSource
organism name: Polyporus umbellatus Fries
derived from organism: polyporus-umbellatus-fries
substance type: sclerotium
family: Polyporaceae

poria-sclerotium-wolfiporia-cocos-ryvarden-et
type: BiologicalSource
organism name: Wolfiporia cocos Ryvarden et
derived from organism: wolfiporia-cocos-ryvarden-et
substance type: sclerotium

prepared-glycyrrhiza-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

processed-aconite-root-aconitum-carmichaeli-debeaux-or
type: BiologicalSource
organism name: Aconitum carmichaeli Debeaux or
derived from organism: aconitum-carmichaeli-debeaux-or
organism part: tuberous root

processed-aconite-root-aconitum-carmichaeli-debeaux
type: BiologicalSource
organism name: Aconitum carmichaeli Debeaux
derived from organism: aconitum-carmichaeli-debeaux
organism part: tuberous root
family: Ranunculaceae

processed-ginger-zingiber-officinale-roscoe
type: BiologicalSource
organism name: Zingiber officinale Roscoe
derived from organism: zingiber-officinale-roscoe
organism part: rhizome
family: Zingiberaceae

prunella-spike-prunella-vulgaris-linn
type: BiologicalSource
organism name: Prunella vulgaris Linn
derived from organism: prunella-vulgaris-linn
substance type: spike

pueraria-root-pueraria-lobata-ohwi
type: BiologicalSource
organism name: Pueraria lobata Ohwi
derived from organism: pueraria-lobata-ohwi
organism part: the root
family: Leguminosae

quercus-bark-quercus-acutissima-carruthers
type: BiologicalSource
organism name: Quercus acutissima Carruthers
derived from organism: quercus-acutissima-carruthers
organism part: the bark

red-ginseng-panax-ginseng-c
type: BiologicalSource
organism name: Panax ginseng C
derived from organism: panax-ginseng-c
organism part: the root

red-ginseng-dilute-sodium-hydroxide-ts
type: BiologicalSource
organism name: dilute sodium hydroxide TS
derived from organism: dilute-sodium-hydroxide-ts
substance type: solution, add 3 mL

red-ginseng-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

rehmannia-root-rehmannia-glutinosa-liboschitz-var
type: BiologicalSource
organism name: Rehmannia glutinosa Liboschitz var
derived from organism: rehmannia-glutinosa-liboschitz-var
organism part: the root

rhubarb-rheum-palmatum-linn
type: BiologicalSource
organism name: Rheum palmatum Linn
derived from organism: rheum-palmatum-linn
organism part: usually the rhizome

rhubarb-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 20 mL

rose-fruit-rosa-multiflora-thunberg
type: BiologicalSource
organism name: Rosa multiflora Thunberg
derived from organism: rosa-multiflora-thunberg
organism part: false or true fruit
family: Rosaceae

rosin-plants-of-pinus-species
type: BiologicalSource
organism name: plants of Pinus species
derived from organism: plants-of-pinus-species
organism part: resin obtained from the exudation
family: Pinaceae

royal-jelly-the-supernatant-liquid
type: BiologicalSource
organism name: the supernatant liquid
derived from organism: the-supernatant-liquid
substance type: solution, pipet 2 mL

royal-jelly-the-internal-standard-solution
type: BiologicalSource
organism name: the internal standard solution
derived from organism: the-internal-standard-solution
substance type: solution, add exactly 2 mL

safflower-carthamus-tinctorius-linn
type: BiologicalSource
organism name: Carthamus tinctorius Linn
derived from organism: carthamus-tinctorius-linn
organism part: tubulous flower

saffron-crocus-sativus-linn
type: BiologicalSource
organism name: Crocus sativus Linn
derived from organism: crocus-sativus-linn
substance type: stigma

saffron-the-standard-solution
type: BiologicalSource
organism name: the standard solution
derived from organism: the-standard-solution
substance type: larger than that

salvia-miltiorrhiza-root-salvia-miltiorrhiza-bunge
type: BiologicalSource
organism name: Salvia miltiorrhiza Bunge
derived from organism: salvia-miltiorrhiza-bunge
organism part: the root
family: Labiatae

salvia-miltiorrhiza-root-the-cork-layer
type: BiologicalSource
organism name: the cork layer
derived from organism: the-cork-layer
substance type: at the outside

sappan-wood-caesalpinia-sappan-linn
type: BiologicalSource
organism name: Caesalpinia sappan Linn
derived from organism: caesalpinia-sappan-linn
substance type: duramen

saussurea-root-saussurea-lappa-clarke
type: BiologicalSource
organism name: Saussurea lappa Clarke
derived from organism: saussurea-lappa-clarke
organism part: the root
family: Compositae

schisandra-fruit-schisandra-chinensis-baillon
type: BiologicalSource
organism name: Schisandra chinensis Baillon
derived from organism: schisandra-chinensis-baillon
organism part: fruit
family: Schisandraceae

schizonepeta-spike-schizonepeta-tenuifolia-briquet
type: BiologicalSource
organism name: Schizonepeta tenuifolia Briquet
derived from organism: schizonepeta-tenuifolia-briquet
substance type: spike
family: Labiatae

scopolia-rhizome-scopolia-japonica-maximowicz
type: BiologicalSource
organism name: Scopolia japonica Maximowicz
derived from organism: scopolia-japonica-maximowicz
organism part: rhizome with root

scopolia-rhizome-diethyl-ether
type: BiologicalSource
organism name: diethyl ether
derived from organism: diethyl-ether
substance type: add 25 mL

scopolia-rhizome-scopolamine-and-atropine-being
type: BiologicalSource
organism name: scopolamine and atropine being
derived from organism: scopolamine-and-atropine-being
substance type: order with the resolution between the peaks

scutellaria-root-scutellaria-baicalensis-georgi
type: BiologicalSource
organism name: Scutellaria baicalensis Georgi
derived from organism: scutellaria-baicalensis-georgi
organism part: the root
family: Labiatae

senega-polygala-senega-linn
type: BiologicalSource
organism name: Polygala senega Linn
derived from organism: polygala-senega-linn
organism part: the root

senna-leaf-cassia-angustifolia-vahl-or
type: BiologicalSource
organism name: Cassia angustifolia Vahl or
derived from organism: cassia-angustifolia-vahl-or
organism part: leaflets

senna-leaf-the-leaf
type: BiologicalSource
organism name: the leaf
derived from organism: the-leaf
substance type: in parallel with the surface

senna-leaf-foreign-matter
type: BiologicalSource
organism name: foreign matter
derived from organism: foreign-matter
organism part: and fruit—When perform the test

senna-leaf-cassia-angustifolia-vahl
type: BiologicalSource
organism name: Cassia angustifolia Vahl
derived from organism: cassia-angustifolia-vahl
organism part: leaflets
family: Leguminosae

sesame-sesamum-indicum-linn
type: BiologicalSource
organism name: Sesamum indicum Linn
derived from organism: sesamum-indicum-linn
organism part: the seed

smilax-rhizome-smilax-glabra-roxburgh
type: BiologicalSource
organism name: Smilax glabra Roxburgh
derived from organism: smilax-glabra-roxburgh
organism part: rhizome
family: Liliaceae

sodium-sulfate-hydrate-sodium-sulfate
type: BiologicalSource
organism name: sodium sulfate
derived from organism: sodium-sulfate
substance type: mainly decahydrate
family: Na2SO4

sophora-root-sophora-flavescens-aiton
type: BiologicalSource
organism name: Sophora flavescens Aiton
derived from organism: sophora-flavescens-aiton
organism part: the root
family: Leguminosae

sweet-hydrangea-leaf-hydrangea-macrophylla-seringe-var
type: BiologicalSource
organism name: Hydrangea macrophylla Seringe var
derived from organism: hydrangea-macrophylla-seringe-var
organism part: leaf and twig

swertia-herb-swertia-japonica-makino
type: BiologicalSource
organism name: Swertia japonica Makino
derived from organism: swertia-japonica-makino
organism part: whole herb
family: Gentianaceae

swertia-herb-this-solution-under-the
type: BiologicalSource
organism name: this solution under the
derived from organism: this-solution-under-the
substance type: run with 10 mL

swertia-herb-these-peaks-being-not
type: BiologicalSource
organism name: these peaks being not
derived from organism: these-peaks-being-not
substance type: order with the resolution

toad-cake-bufo-gargarizans-cantor-or
type: BiologicalSource
organism name: Bufo gargarizans Cantor or
derived from organism: bufo-gargarizans-cantor-or
substance type: parotoid secretion

toad-cake-the-internal-standard-solution
type: BiologicalSource
organism name: the internal standard solution
derived from organism: the-internal-standard-solution
substance type: solution, add exactly 5 mL

toad-cake-bufo-gargarizans-cantor
type: BiologicalSource
organism name: Bufo gargarizans Cantor
derived from organism: bufo-gargarizans-cantor
substance type: parotoid secretion
family: Bufonidae

tragacanth-hydrochloric-acid
type: BiologicalSource
organism name: hydrochloric acid
derived from organism: hydrochloric-acid
substance type: formed, add 5 mL

tragacanth-astragalus-gummifer-labillardi
type: BiologicalSource
organism name: Astragalus gummifer Labillardi
derived from organism: astragalus-gummifer-labillardi
substance type: trunks

tribulus-fruit-tribulus-terrestris-linn
type: BiologicalSource
organism name: Tribulus terrestris Linn
derived from organism: tribulus-terrestris-linn
organism part: fruit

trichosanthes-root-trichosanthes-kirilowii-maximowicz
type: BiologicalSource
organism name: Trichosanthes kirilowii Maximowicz
derived from organism: trichosanthes-kirilowii-maximowicz
organism part: the root

turmeric-curcuma-longa-linn
type: BiologicalSource
organism name: Curcuma longa Linn
derived from organism: curcuma-longa-linn
organism part: rhizome

uncaria-hook-ammonia-solution
type: BiologicalSource
organism name: ammonia solution
derived from organism: ammonia-solution
substance type: solution add 1 mL

wood-creosote-phenols-obtained-from-by
type: BiologicalSource
organism name: phenols obtained from by
derived from organism: phenols-obtained-from-by
substance type: a mixture

wood-creosote-dry-distillation-of-stems
type: BiologicalSource
organism name: dry distillation of stems
derived from organism: dry-distillation-of-stems

adsorbed-diphtheria-purified-pertussis-tetanus-combined-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Adsorbed Diphtheria-Purified Pertussis-Tetanus Combined Vaccine
  ja: 沈降精製百日せきジフテリア破傷風混合ワクチン
monograph id: JP18-adsorbed-diphtheria-purified-pertussis-tetanus-combined-vaccine
publisher: JP
status: Official
version: 18
appearance:
  en: Adsorbed Diphtheria-Purified Pertussis-Teta-nus Combined Vaccine becomes a homogeneous, white tur-bid liquid on shaking. Adsorbed Diphtheria-Tetanus Combined Toxoid

adsorbed-hepatitis-b-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Adsorbed Hepatitis B Vaccine
  ja: 沈降 B 型肝炎ワクチン
monograph id: JP18-adsorbed-hepatitis-b-vaccine
publisher: JP
status: Official
version: 18
appearance:
  en: Adsorbed Hepatitis B Vaccine becomes a ho-mogeneous, whitish turbid liquid on shaking. L-Histidine

adsorbed-purified-pertussis-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Adsorbed Purified Pertussis Vaccine
  ja: 沈降精製百日せきワクチン
monograph id: JP18-adsorbed-purified-pertussis-vaccine
publisher: JP
status: Official
version: 18
appearance:
  en: Adsorbed Purified Pertussis Vaccine forms a homogeneous, white turbidity on shaking. Pethidine Hydrochloride

albumin-tannate
type: BiologicalSubstanceMonograph
pref label:
  en: Albumin Tannate
  ja: タンニン酸アルブミン
monograph id: JP18-albumin-tannate
publisher: JP
status: Official
version: 18
appearance:
  en: Albumin Tannate occurs as a light brown powder. It is odorless, or has a faint, characteristic odor. It is practically insoluble in water and in ethanol (95). It dissolves in sodium hydroxide TS with turbidity.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 0.1 g of Albumin Tannate add 10 amount amount amount amount amount mL of ethanol (95), and heat in a water bath for 3 minutes Total volume 1000 mL 1000 mL 1000 mL 1000 mL 1000 mL Changing mobile phases: When the procedure is run with 20 mL of the standard solution under the above operating conditions, switchover in sequence to mobile phases A, B, C, D and E so that aspartic acid, threonine, serine, glutamic acid, glycine, alanine, cystine, valine, methionine, isoleu-cine, leucine, tyrosine, phenylalanine, lysine, ammonia, histidine, and arginine are eluted in this order with the reso-lution between the peaks of isoleucine and leucine being not less than 1.2. Reaction reagents: Dissolve 204 g of lithium acetate dihy-drate in water, add 123 mL of acetic acid (100) and 401 mL of 1-methoxy-2-propanol, and water to make 1000 mL, introduce nitrogen for 10 minutes, and use this solution as solution (I). Separately, add 39 g of ninhydrin to 979 mL of 1-methoxy-2-propanol, introduce nitrogen for 5 minutes, add 81 mg of sodium borohydride, introduce nitrogen for 30 minutes, and use this solution as solution (II). To 1 volume of solution (I) add 1 volume of solution (II). Prepare before use. Flow rate of mobile phase: 0.20 mL per minute. Flow rate of reaction reagent: 0.24 mL per minute. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating conditions, the resolution between the peaks of glycine and alanine is not less than 1.2. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviations of the peak height and retention time of each amino acid obtained from the standard solution are not more than 5.0z and not more than 1.0z, respectively. Loss on drying <2.41> Not more than 0.3z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—Shake 1.0 g of Albumin Tannate with 50 mL of water for 5 minutes, and filter. To 25 mL of the fil-trate add 1.0 mL of 0.1 mol/L sodium hydroxide VS and 2 drops of phenolphthalein TS: a red color develops. (2) Fats—To 2.0 g of Albumin Tannate add 20 mL of petroleum benzine, shake vigorously for 15 minutes, and filter. Evaporate 10 mL of the filtrate on a water bath: the mass of the residue is not more than 50 mg. Loss on drying <2.41> Not more than 6.0z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 1.0z (0.5 g). Digestion test To 1.00 g of Albumin Tannate add 0.25 g of saccharated pepsin and 100 mL of water, shake well, and allow to stand for 20 minutes at 40 ± 19C in a water bath. Add 1.0 mL of dilute hydrochloric acid, shake, and allow to stand for 3 hours at 40 ± 19C. Cool rapidly to ordinary tem-perature, and filter. Wash the residue with three 10-mL por-tions of water, dry in a desiccator (silica gel) for 18 hours, and dry at 1059C for 5 hours: the mass of the residue is 0.50 to 0.58 g.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 90 mg of L-Alanine, previ-ously dried, dissolve in 3 mL of formic acid, add 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 8.909 mg of C3H7NO2
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dihydroergotoxine-mesilate
type: BiologicalSubstanceMonograph
pref label:
  en: Dihydroergotoxine Mesilate
  ja: ジヒドロエルゴトキシンメシル酸塩
monograph id: JP18-dihydroergotoxine-mesilate
publisher: JP
status: Official
version: 18
definition:
  en: Dihydroergotoxine Mesilate contains not less than 97.
appearance:
  en: Dihydroergotoxine Mesilate occurs as a white to pale yellow powder. It is soluble in methanol, sparingly soluble in ethanol (95), slightly soluble in water, in acetonitrile and in chloroform, and practically insoluble in diethyl ether. JP XVIII Official Monographs / Dihydroergotoxine Mesilate 861
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Dihydroergotoxine Mesilate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios of the peak areas of dihydroergocornine, dihydro-a-ergocryptine, dihydroergocristine and dihydro-b-ergocryptine to the peak area of the internal standard of these solutions. Amount (mg) of dihydroergotoxine mesilate D Optical rotation <2.49> [a]20: ＋11.0 – ＋15.09(0.2 g calcu- ＝ MS × (QTA ＋ QTB ＋ QTC ＋ QTD)/ lated on the anhydrous basis, dilute ethanol, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.10 g of Dihydroergotoxine Mesilate in 20 mL of water: the solu-tion is clear and the color of the solution is not more intense than that of the following control solution. Control solution: To a mixture of 1.0 mL of Cobalt (II) Chloride CS, 0.4 mL of Copper (II) Sulfate CS and 2.4 mL of Iron (III) Chloride CS add diluted hydrochloric acid (1 in 40) to make exactly 200 mL. Heavy metals <1.07>—Proceed with 1.0 g of Di- hydroergotoxine Mesilate according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Weigh accurately 0.100 g of Di-hydroergotoxine Mesilate, dissolve it in a mixture of chlo-roform and methanol (9:1) to make exactly 5 mL, and use this solution as the sample solution. Separately, weigh accu-rately 10 mg of dihydroergocristine mesilate for thin-layer chromatography, and dissolve in a mixture of chloroform and methanol (9:1) to make exactly 100 mL. Pipet 6 mL, 4 mL and 2 mL of this solution, add a mixture of chloroform and methanol (9:1) to make exactly 10 mL, respectively, and use these solutions as the standard solutions (1), (2) and (3), respectively. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03> without putting the filter paper in the developing vessel. Spot 5 mL each of the sample solution and the standard solutions (1), (2) and on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, ethyl acetate, methanol and ammonia solution (28) (50:50:3:1) to a distance of about 15 cm, and dry the plate with the aid of a cool air stream. Immediately after that, develop the plate again with a newly prepared mixture of dichloromethane, ethyl acetate, methanol and ammonia solution (28) (50:50:3:1) to a distance of about 15 cm, and dry the plate within 1 minute with the aid of a cool air stream. Spray evenly p-dimethylaminobenzal-deh…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Dihydroergotoxine mesilate—Weigh accurately about 30 mg each of Dihydroergotoxine Mesilate and Di-hydroergotoxine Mesilate RS, and dissolve them separately in a suitable amount of a mixture of water and acetonitrile (3:1). To these solutions add exactly 10 mL of the internal standard solution and an amount of a mixture of water and acetonitrile (3:1) to make 50 mL, and use these solutions as the sample solution and the standard solution. Perform the test with 20 mL of the sample solution and standard solution (QSA ＋ QSB ＋ QSC ＋ QSD) MS: Amount (mg) of Dihydroergotoxine Mesilate RS taken, calculated on the anhydrous basis QTA: Ratio of the peak area of dihydroergocornine to that of the internal standard of the sample solution × 659.80 QTB: Ratio of the peak area of dihydro-a-ergocryptine to that of the internal standard of the sample × 673.83 QTC: Ratio of the peak area of dihydroergocristine to that of the internal standard of the sample solution × 707.85 QTD: Ratio of the peak area of dihydro-b-ergocryptine to that of the internal standard of the sample solution × 673.83 QSA: Ratio of the peak area of dihydroergocornine to that of the internal standard of the standard solution × 659.80 QSB: Ratio of the peak area of dihydro-a-ergocryptine to that of the internal standard of the standard solution × 673.83 QSC: Ratio of the peak area of dihydroergocristine to that of the internal standard of the standard solution × 707.85 QSD: Ratio of the peak area of dihydro-b-ergocryptine to that of the internal standard of the standard solution × 673.83 Internal standard solution—Dissolve 0.04 g of chloram-phenicol in a mixture of water and acetonitrile (3:1) to make 250 mL. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant tempe…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

dried-thyroid
type: BiologicalSubstanceMonograph
pref label:
  en: Dried Thyroid
  ja: 乾燥甲状腺
monograph id: JP18-dried-thyroid
publisher: JP
status: Official
version: 18
definition:
  en: Dried Thyroid is the fresh thyroid gland, previously deprived of connective tissue and fat, minced, dried rapidly at a temperature not above 509C, and pow-dered, or diluted with suitable diluents. It is obtained from domesticated animals that are used for food by man. It contains not less than 0.
appearance:
  en: Dried Thyroid occurs as a light yellow to grayish brown powder. It has a slight, characteristic, meat-like odor.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Mount Dried Thyroid in diluted formalde-hyde solution (1 in 10), stain in hematoxylin TS for 10 to 30 minutes, wash with water, soak in a mixture of 1 mL of hy-drochloric acid and 99 mL of diluted ethanol (7 in 10) for 5 to 10 seconds, and again wash with water for about 1 hour. Stain in a solution of eosin Y (1 in 100) for 1 to 5 minutes, wash with water, dehydrate, and soak successively in diluted ethanol (7 in 10) for 5 to 10 seconds, in diluted ethanol (4 in 5) for 5 to 10 seconds, in diluted ethanol (9 in 10) for 1 to 2 minutes, in ethanol (95) for 1 to 5 minutes then in ethanol (99.5) for 1 to 5 minutes. Interpenetrate in xylene, seal with balsam, and examine under a microscope: epithelial nuclei forming follicles peculiar to the thyroid gland are observed.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Inorganic iodides—Mix 1.0 g of Dried Thyroid with 10 mL of a saturated solution of zinc sulfate, shake for 5 minutes, and filter. To 5 mL of the filtrate add 0.5 mL of starch TS, 4 drops of sodium nitrite TS and 4 drops of dilute sulfuric acid with thorough shaking: no blue color is pro-duced. (2) Fat—Extract 1.0 g of Dried Thyroid with diethyl ether for 2 hours using a Soxhlet extractor. Evaporate the diethyl ether extract, and dry the residue at 1059C to con-stant mass: the mass of the residue is not more than 30 mg. Loss on drying <2.41> Not more than 6.0z (1 g, 1059C, constant mass). Total ash <5.01> Not more than 5.0z (0.5 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Transfer about 1 g of Dried Thyroid, accurately weighed, to a crucible, add 7 g of potassium carbonate, mix carefully, and gently tap the crucible on the table to compact the mixture. Overlay with 10 g of potassium carbonate, and compact again thoroughly by tapping. Place the crucible in a muffle furnace preheated to a temperature between 6009C and 7009C, and ignite the mixture for 25 minutes. Cool, add 20 mL of water, heat gently to boiling, and filter into a flask. To the residue add 20 mL of water, boil, and filter into the same flask. Rinse the crucible and the char on the funnel with boiling water until the filtrate measures 200 mL. Add slowly 7 mL of freshly prepared bromine TS, 40 mL of di-luted phosphoric acid (1 in 2), and boil until starch iodide paper is no longer colored blue by the evolved gas. Wash down inside of the flask with water, and continue boiling for 5 minutes. During the boiling add water from time to time to maintain a volume at not less than 200 mL. Cool, add 5 mL of a solution of phenol (1 in 20), again rinse inside of the flask with water, and allow to stand for 5 minutes. Add 2 mL of diluted phosphoric acid (1 in 2) and 5 mL of potas- ‌sium iodide TS, and titrate <2.50> immediately the liberated iodine with 0.01 mol/L sodium thiosulfate VS (indicator: 3 mL of starch TS). Perform a blank determination in the same manner, and make any necessary correction.‌ Each mL of 0.01 mol/L sodium thiosulfate VS ＝ 0.2115 mg of I
storage conditions:
  en: Containers—Tight containers.

freeze-dried-bcg-vaccine-for-percutaneous-use
type: BiologicalSubstanceMonograph
pref label:
  en: Freeze-dried BCG Vaccine (for Percutaneous Use)
  ja: 乾燥 BCG ワクチン
monograph id: JP18-freeze-dried-bcg-vaccine-for-percutaneous-use
publisher: JP
status: Official
version: 18
definition:
  en: Freeze-dried BCG Vaccine (for Percutaneous Use) is a preparation for injection which is dissolved before use. It contains live bacteria derived from a culture of the bacillus of Calmette and Gueárin.
appearance:
  en: Freeze-dried BCG Vaccine (for Percutaneous Use) becomes a white to light yellow, turbid liquid on addi-tion of solvent. Beclometasone Dipropionate

freeze-dried-inactivated-tissue-culture-rabies-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Freeze-dried Inactivated Tissue Culture Rabies Vaccine
  ja: 乾燥組織培養不活化狂犬病ワクチン
monograph id: JP18-freeze-dried-inactivated-tissue-culture-rabies-vaccine
publisher: JP
status: Official
version: 18
appearance:
  en: Freeze-dried Inactivated Tissue Culture Rabies Vaccine becomes a colorless or light yellow-red clear liquid on addition of solvent. Ranitidine Hydrochloride

freeze-dried-live-attenuated-measles-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Freeze-dried Live Attenuated Measles Vaccine
  ja: 乾燥弱毒生麻しんワクチン
monograph id: JP18-freeze-dried-live-attenuated-measles-vaccine
publisher: JP
status: Official
version: 18
definition:
  en: Freeze-dried Live Attenuated Measles Vaccine is a preparation for injection which is dissolved before use. It contains live attenuated measles virus.
appearance:
  en: Freeze-dried Live Attenuated Measles Vaccine becomes a colorless, yellowish or reddish clear liquid on ad-dition of solvent. Meclofenoxate Hydrochloride

freeze-dried-live-attenuated-mumps-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Freeze-dried Live Attenuated Mumps Vaccine
  ja: 乾燥弱毒生おたふくかぜワクチン
monograph id: JP18-freeze-dried-live-attenuated-mumps-vaccine
publisher: JP
status: Official
version: 18
appearance:
  en: Freeze-dried Live Attenuated Mumps Vaccine becomes a clear, colorless, yellowish or reddish liquid on ad-dition of solvent. Mupirocin Calcium Hydrate

freeze-dried-live-attenuated-rubella-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Freeze-dried Live Attenuated Rubella Vaccine
  ja: 乾燥弱毒生風しんワクチン
monograph id: JP18-freeze-dried-live-attenuated-rubella-vaccine
publisher: JP
status: Official
version: 18
definition:
  en: Freeze-dried Live Attenuated Rubella Vaccine is a preparation for injection which is dissolved before use. It contains live attenuated rubella virus.
appearance:
  en: Freeze-dried Live Attenuated Rubella Vaccine becomes a colorless, yellowish or reddish, clear liquid on ad-dition of solvent. Saccharated Pepsin

freeze-dried-smallpox-vaccine-prepared-in-cell-culture
type: BiologicalSubstanceMonograph
pref label:
  en: Freeze-dried Smallpox Vaccine Prepared in Cell Culture
  ja: 乾燥細胞培養痘そうワクチン
monograph id: JP18-freeze-dried-smallpox-vaccine-prepared-in-cell-culture
publisher: JP
status: Official
version: 18
definition:
  en: Freeze-dried Smallpox Vaccine Prepared in Cell Culture is a preparation for injection which is dis-solved before use. It contains live vaccinia virus.
appearance:
  en: Freeze-dried Smallpox Vaccine Prepared in Cell Culture becomes a reddish clear liquid on addition of solvent. Sodium Acetate Hydrate

freeze-dried-smallpox-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Freeze-dried Smallpox Vaccine
  ja: 乾燥痘そうワクチン
monograph id: JP18-freeze-dried-smallpox-vaccine
publisher: JP
status: Official
version: 18
definition:
  en: Freeze-dried Smallpox Vaccine is a preparation for injection which is dissolved before use. It contains live vaccinia virus.
appearance:
  en: Freeze-dried Smallpox Vaccine becomes a white to gray, turbid liquid on addition of solvent. Freeze-dried Smallpox Vaccine Prepared in Cell Culture

heparin-calcium
type: BiologicalSubstanceMonograph
pref label:
  en: Heparin Calcium
  ja: ヘパリンカルシウム
monograph id: JP18-heparin-calcium
publisher: JP
status: Official
version: 18
definition:
  en: Heparin Calcium is the calcium salt of sulfated glycosaminoglycans composed of disaccharide units of D-glucosamine and uronic acid (L-iduronic acid or D- glucuronic acid) obtained from the intestinal mucosa of healthy edible swine. It contains not less than 180 Heparin Units (anti-factor IIa activity) per mg and not less than 8.
appearance:
  en: Heparin Calcium occurs as a white to grayish brown, powder or grains. It is freely soluble in water, and practically insoluble in ethanol (99.5). It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 10 mg of Heparin Calcium in 5 mL of water, and add 0.1 mL of 1 mol/L hydrochloric acid TS and 5 mL of toluidine blue O solution (1 in 20,000): a purple to red-purple color develops. Dissolve 1 mg each of Heparin Calcium and Heparin Sodium for Identification RS in 1 mL of water, and use these solutions as the sample solution and the standard solu-tion, respectively. Perform the test with 20 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions: the retention time for the major peak from the sam-ple solution and standard solution is identical. Operating conditions— Detector, column, column temperature, mobile phases A and B, flowing of mobile phase and flow rate: Proceed as di-rected under the operating conditions in Purity (9). System suitability— System performance: Dissolve 1.0 mg of Heparin Sodium for Identification RS in 0.60 mL of water. Dissolve 0.10 mg of Over-sulfated Chondroitin Sulfate for System Suitability RS in 0.20 mL of water. Dissolve 1.0 mg of dermatan sulfate in 2.0 mL of water. To 90 mL of the solution of Heparin So-dium for Identification RS add 30 mL each of the solutions of Over-sulfated Chondroitin Sulfate for System Suitability RS and dermatan sulfate, and mix. When the procedure is run with 20 mL of the mixture under the above operating conditions, dermatan sulfate, heparin and over-sulfated chondroitin sulfate are eluted in this order with the resolu-tion between the peaks of dermatan sulfate and heparin being not less than 1.0 and that between the peaks of heparin and over-sulfated chondroitin sulfate being not less than 1.5. A solution of 50 mg of Heparin Calcium in 5 mL of water responds to Qualitative Tests <1.09> for calcium salt. pH <2.54> Dissolve 1.0 g of Heparin Calcium in 100 mL of water: the pH of the solution is between 6.0 and 8.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Heparin Calcium in 20 mL of water: the solution is clear. Determine the absorbance of this solution at 400 nm as di-rected under Ultraviolet-visible Spectrophotometry <2.24>: the absorbance is not more than 0.05. Chloride <1.03>—Perform the test with 0.5 g of Heparin Calcium. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Heavy metals <1.07>—Proceed with 0.5 g of Heparin Calcium according to Method 2, and perform the test. Pre-pare the control solution with 1.5 mL of Standard Lead So-lution (not more than 30 ppm). Barium—Dissolve 30 mg of Heparin Calcium in 3.0 mL of water, and use this solution as the sample solution. To 1.0 mL of the sample solution add 3 drops of dilute sul-furic acid, and allow to stand for 10 minutes: no turbidity is produced. Total nitrogen—Weigh accurately about 0.1 g of Heparin Calcium, previously dried, and perform the test as directed under Nitrogen Determination <1.08>: the amount of nitrogen (N: 14.01) is not more than 3.0z. Protein—(i) Sodium carbonate solution: To 4 volumes of a mixture of sodium hydroxide solution (1 in 100) and anhydrous sodium carbonate solution (1 in 20) (1:1) add 1 volume of water. Copper sulfate solution: To 4 volumes of a mixture of copper (II) sulfate pentahydrate solution (1 in 80) and sodium tartrate dihydrate solution (149 in 5000) (1:1) add 1 volume of water. Alkaline copper solution for heparin: Mix 50 volumes of the sodium carbonate solution and 1 volume of the copper sulfate solution. Prepare before using. Procedure: Use a solution of Heparin Calcium (1 in 200) as the sample solution. Use a solution of bovine serum albumin (1 in 40,000) as the standard solution. To exactly 1 mL each of the sample solution and standard solution add exactly 5 mL of the alkaline copper solution for heparin, mix, and allow them to stand at room temperature for 10 minutes. To each of these solutions add exactly 0.5 mL of …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Heparin Substrate solution: Dissolve 25 mg of H-D-pheny-lalanyl-L-pipecolyl-L-arginyl-p-nitroanilide dihydrochloride in 32.0 mL of water. Anti-thrombin solution (for heparin assay): Dissolve human anti-thrombin in water so that each mL contains 1 IU. Dilute this solution to an appropriate dilution factor of approximately more than 16 times with the buffer solution, and designate this solution as the anti-thrombin solution (for heparin assay). The dilution factor with the buffer solution is adjusted so that the absorbance of reaction solution with the blank solution (average of five tubes) is not more than 2.0, and that of reaction solution with S4 (0.020 Unit/mL heparin standard solution) (average of two tubes) is not less than 0.2 and not more than 1.0 when the test is performed according to the Assay. The absorbance is measured with 1 cm light path in length. Factor IIa solution: Add an equivalent volume of water to the buffer solution, and use this solution as the fac-tor IIa diluent. Dissolve factor IIa in the factor IIa diluent to make a solution so that each mL contains 20 IU. Dilute this solution to an appropriate dilution factor of approximately less than 4 times with the factor IIa diluent, and designate this solution as the factor IIa solution. Adjust the dilution factor with the factor IIa diluent so that the absorbance of reaction solution with the blank solution (average of five tubes) is not more than 2.0, and that of reaction solution with S4 (0.020 Unit/mL heparin standard solution) (average of two tubes) is not less than 0.2 and not more than 1.0 when the test is performed according to the Assay. The absorbance is measured with 1 cm light path in length. Buffer solution: Dissolve 6.1 g of 2-amino-2-hydrox-ymethyl-1,3-propanediol, 10.2 g of sodium chloride, 2.8 g of disodium dihydrogen ethylenediamine tetraacetate dihydrate and 1.0 g of polyethylene glycol 6000 in 800 mL of water, adjust to pH 8.4 with 1 mol/L hydrochloric acid TS, and add water …
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

heparin-sodium
type: BiologicalSubstanceMonograph
pref label:
  en: Heparin Sodium
  ja: ヘパリンナトリウム
monograph id: JP18-heparin-sodium
publisher: JP
status: Official
version: 18
definition:
  en: Heparin Sodium is a sodium salt of sulfated glycosaminoglycans composed of disaccharide units of D-glucosamine and uronic acid (L-iduronic acid or D- glucuronic acid) obtained from the intestinal mucosa of healthy edible swine. It contains not less than 180 Heparin Units (anti-factor IIa activity) per mg, calculated on the dried basis.
appearance:
  en: Heparin Sodium occurs as a white to grayish brown, powder or grains. It is odorless. It is soluble in water, and practically insoluble in ethanol (95) and in diethyl ether. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Dissolve 1 mg each of Heparin Sodium and Heparin Sodium for Identification RS in 1 mL of water, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions: the retention time for the major peak from the sample solution and standard solution is identical. Operating conditions— Detector, column, column temperature, mobile phases A and B, flowing of mobile phase and flow rate: Proceed as di-rected under the operating conditions in Purity (7). System suitability— System performance: Dissolve 1.0 mg of Heparin Sodium for Identification RS in 0.60 mL of water. Dissolve 0.10 mg of Over-sulfated Chondroitin Sulfate for System Suitability RS in 0.20 mL of water. Dissolve 1.0 mg of dermatan sulfate in 2.0 mL of water. To 90 mL of the solution of Heparin So-dium for Identification RS add 30 mL each of the solutions of Over-sulfated Chondroitin Sulfate for System Suitability RS and dermatan sulfate, and mix. When the procedure is run with 20 mL of the mixture under the above operating conditions, dermatan sulfate, heparin and over-sulfated chondroitin sulfate are eluted in this order with the resolu-tion between the peaks of dermatan sulfate and heparin being not less than 1.0 and that between the peaks of heparin and over-sulfated chondroitin sulfate being not less than 1.5. pH <2.54> The pH of a solution of 1.0 g of Heparin So-dium in 100 mL of water is between 6.0 and 8.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Heparin Sodium in 20 mL of water: the solution is clear and colorless to light yellow. Barium—Dissolve 30 mg of Heparin Sodium in 3.0 mL of water, and use this solution as the sample solution. To 1.0 mL of the sample solution add 3 drops of dilute sul-furic acid, and allow to stand for 10 minutes: no turbidity is produced. Total nitrogen—Weigh accurately about 0.1 g of Heparin Sodium, previously dried at 609C for 3 hours under reduced pressure, and perform the test as directed under Nitrogen Determination <1.08>: the amount of nitrogen (N: 14.01) is not more than 3.0z. Protein—(i) Sodium carbonate solution: To 4 volumes of a mixture of sodium hydroxide solution (1 in 100) and anhydrous sodium carbonate solution (1 in 20) (1:1) add 1 volume of water. Copper sulfate solution: To 4 volumes of a mixture of copper (II) sulfate pentahydrate solution (1 in 80) and sodium tartrate dihydrate solution (149 in 5000) (1:1) add 1 volume of water. Alkaline copper solution for heparin: Mix 50 volumes of the sodium carbonate solution and 1 volume of the copper sulfate solution. Prepare before using. Procedure: Use a solution of Heparin Sodium (1 in 200) as the sample solution. Use a solution of bovine serum albumin (1 in 40,000) as the standard solution. To exactly 1 mL each of the sample solution and standard solution add exactly 5 mL of the alkaline copper solution for heparin, mix, and allow them to stand at room temperature for 10 minutes. To each of these solutions add exactly 0.5 mL of diluted Folin's TS (1 in 2), shake, and allow them to stand at room temperature for 30 minutes. Determine the absor-bances at 750 nm of these solutions as directed under Ultra-violet-visible Spectrophotometry <2.24> using water as the blank: the absorbance of the solution obtained from the sample solution is not more than that of the solution from the standard solution. Nucleic acid—Dissolve 40 mg of Heparin Sodium in 10 mL of water, and deter…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Substrate solution: Dissolve 25 mg of H-D-phenylalanyl-L-pipecolyl-L-arginyl-p-nitroanilide dihydro-chloride in 32.0 mL of water. Anti-thrombin solution (for heparin assay): Dissolve human anti-thrombin in water so that each mL contains 1 IU. Dilute this solution to an appropriate dilution factor of approximately more than 16 times with the buffer solution, and designate this solution as the anti-thrombin solution (for heparin assay). The dilution factor with the buffer solution is adjusted so that the absorbance of reaction solution with the blank solution (average of five tubes) is not more than 2.0, and that of reaction solution with S4 (0.020 Unit/mL heparin standard solution) (average of two tubes) is not less than 0.2 and not more than 1.0 when the test is performed according to the Assay. The absorbance is measured with 1 cm light path in length. Factor IIa solution: Add an equivalent volume of water to the buffer solution, and use this solution as the fac-tor IIa diluent. Dissolve factor IIa in the factor IIa diluent to make a solution so that each mL contains 20 IU. Dilute this solution to an appropriate dilution factor of approximately JP XVIII Official Monographs / Heparin Sodium 1103 less than 4 times with the factor IIa diluent, and designate this solution as the factor IIa solution. Adjust the dilution factor with the factor IIa diluent so that the absorbance of reaction solution with the blank solution (average of five tubes) is not more than 2.0, and that of reaction solution with S4 (0.020 Unit/mL heparin standard solution) (average of two tubes) is not less than 0.2 and not more than 1.0 when the test is performed according to the Assay. The absorbance is measured with 1 cm light path in length. Buffer solution: Dissolve 6.1 g of 2-amino-2-hydrox-ymethyl-1,3-propanediol, 10.2 g of sodium chloride, 2.8 g of disodium dihydrogen ethylenediamine tetraacetate dihydrate and 1.0 g of polyethylene glycol 6000 in 800 mL of water, adjust to pH 8.4 with 1 mol…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

human-normal-immunoglobulin
type: BiologicalSubstanceMonograph
pref label:
  en: Human Normal Immunoglobulin
  ja: 人免疫グロブリン
monograph id: JP18-human-normal-immunoglobulin
publisher: JP
status: Official
version: 18
appearance:
  en: Human Normal Immunoglobulin is a clear, colorless or yellow-brown liquid. Hydralazine Hydrochloride
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of Hydralazine Hy-drochloride, previously dried, transfer it to a glass-stoppered flask, dissolve in 25 mL of water, add 25 mL of hydrochloric acid, cool to room temperature, add 5 mL of chloroform, and titrate <2.50> with 0.05 mol/L potassium iodate VS while shaking until the purple color of the chloroform layer disappears. The end point is reached when the red-purple color no more reappears in the chloroform layer within 5 minutes after the layer has been decolorized. Each mL of 0.05 mol/L potassium iodate VS ＝ 9.832 mg of C H N .HCl 8 8 4 Description Human Normal Immunoglobulin is a clear, colorless or yellow-brown liquid. Hydralazine Hydrochloride

influenza-ha-vaccine
type: BiologicalSubstanceMonograph
pref label:
  en: Influenza HA Vaccine
  ja: インフルエンザ HA ワクチン
monograph id: JP18-influenza-ha-vaccine
publisher: JP
status: Official
version: 18
definition:
  en: Influenza HA Vaccine is a liquid for injection con-taining hemagglutinin of influenza virus. It conforms to the requirements of Influenza HA Vaccine in the Minimum Requirements for Biological Products. Description Influenza HA Vaccine is a clear liquid or a slightly whitish turbid liquid. A chain C99H153N25O35S4: 2381.68 B chain C158H234N40O42S2: 3429.92 [11061-68-0] Insulin Human (Genetical Recombination) is a recombinant human insulin. It is a peptide composed of A chain consisting of 21 amino acid residues and B chain consisting of 30 amino acid residues. It contains not less than 27.
appearance:
  en: Influenza HA Vaccine is a clear liquid or a slightly whitish turbid liquid. A chain C99H153N25O35S4: 2381.68 B chain C158H234N40O42S2: 3429.92 [11061-68-0] Insulin Human (Genetical Recombination) is a recombinant human insulin. It is a peptide composed of A chain consisting of 21 amino acid residues and B chain consisting of 30 amino acid residues. It contains not less than 27.5 Insulin Units per mg, calculated on the dried basis. Description Insulin Human (Genetical Recombination) occurs as a white powder. It is practically insoluble in water and in ethanol (95). It dissolves in 0.01 mol/L hydrochloric acid TS and in sodium hydroxide TS with decomposition. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Weigh accurately a suitable amount of Insu-lin Human (Genetical Recombination), and dissolve in 0.01 mol/L hydrochloric acid TS to make a solution so that each mL contains 2.0 mg. Transfer 500 mL of this solution into a clean test tube, add 2.0 mL of HEPES buffer solution (pH 7.5) and 400 mL of V8-protease TS, incubate at 259C for 6 hours, then add 2.9 mL of ammonium sulfate buffer solu-tion to stop the reaction, and use this solution as the sample solution. Separately, proceed with Insulin Human RS in the same manner as above, and use this solution as the standard solution. Perform the test with 50 mL each of the sample so-lution and standard solution as directed under Liquid Chro-matography <2.01> according to the following conditions, and compare the chromatograms obtained from these solu-tions: a similar peak is observed at the same retention time in the both chromatograms. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 214 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 10 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase A: A mixture of water, ammonium sulfate buffer solution and acetonitrile (7:2:1). Mobile phase B: A mixture of water, acetonitrile and am-monium sulfate buffer solution (2:2:1). Flowing of mobile phase: Change the mixing ratio of the mobile phase A and B linearly from 9:1 to 3:7 in 60 minutes after sample injection, further change to 0:10 linearly in 5 minutes, and then flow the mobile phase B only for 5 minutes. Flow rate: 1.0 mL per minute. System suitability— System performance: When the procedure is run with 50 mL of the standard solution under the above operating con- ditions, the symmetry factor of the two larger peaks which appear next to the first peak just after the solvent peak are not more than 1.5 respectively, and the resolution between these pe…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Related substances—Perform this procedure rapidly. Dissolve 7.5 mg of Insulin Human (Genetical Recombination) in 2 mL of 0.01 mol/L hydrochloric acid TS, and use this solution as the sample solution. Perform the test with 20 mL of the sample solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine the peak area of human insulin, A1, the peak area of the desamido substance having the relative retention time of about 1.3 to human insulin, AD, and the total area of the peaks other than the solvent peak, AT: the amounts of the desamido substance and related substances other than the desamido substance are not more than 2.0z, respectively. Previously, perform the test with 0.01 mol/L hydrochloric acid TS in the same manner to confirm the sol-vent peak. Amount (z) of the desamido substance ＝ AD/AT × 100 Amount (z) of related substances other than the desamido substance ＝ [{AT － (A1 ＋ AD)}/AT] × 100 Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 214 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase A: A mixture of phosphoric acid-sodium sulfate buffer solution (pH 2.3) and acetonitrile for liquid chromatography (41:9). Mobile phase B: A mixture of phosphoric acid-sodium sul-fate buffer solution (pH 2.3) and acetonitrile for liquid chro-matography (1:1). Flowing of mobile phase: Flow a mixture of the mobile phase A and B (78:22) for 36 minutes before and after the sample injection, then change the mixing ratio to 33:67 linearly in 25 minutes, and maintain this ratio for 6 minutes. Then flow the first mixture (78:22) for the next 15 minutes. Adjust the mixing ratio of the first mixture so that the reten-tion time of human insulin is about 25 minutes. Flow rate: 1.0 mL per minute. Ti…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform this procedure quickly. Weigh accurately about 7.5 mg of Insulin Human (Genetical Recombination), dissolve in 0.01 mol/L hydrochloric acid TS to make exactly 5 mL, and use this solution as the sample solution. Sepa-rately, weigh accurately a suitable amount of Insulin Human RS, dissolve exactly in 0.01 mol/L hydrochloric acid TS to make a solution so that each mL contains about 40 Insulin Units, and use this solution as the standard solution. Per-form the test with exactly 20 mL each of the sample solution JP XVIII Official Monographs / Insulin Human (Genetical Recombination) Injection 1157 and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and de-termine the peak areas of human insulin, ATI and ASI, and the peak areas of the desamido substance having the relative retention time of 1.3 to human insulin, ATD and ASD, respec-tively, of these solutions. ‌Amount (Insulin Unit/mg) of human insulin (C257H383N65O77S6) ＝ (MS × F )/D × (ATI ＋ ATD)/(ASI ＋ ASD) × 5/MT F: Labeled unit (Insulin Unit/mg) of Insulin Human RS D: Volume (mL) of 0.01 mol/L hydrochloric acid TS used to dissolve the reference standard MT: Amount (mg) of Insulin Human (Genetical Recombi-nation) taken, calculated on the dried basis MS: Amount (mg) of Insulin Human RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 214 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of phosphoric acid-sodium sul-fate buffer solution (pH 2.3) and acetonitrile for liquid chro-matography (3:1). Adjust the mixing ratio of the component of the mobile phase so that the retention time of human in-sulin is between 10 minutes and 17 minutes. Flow rate: 1.0 mL per minute. System suitability— System performance: Wh…
storage conditions:
  en: Containers—Tight containers. Storage—Not exceeding －209C.

insulin-aspart-genetical-recombination
type: BiologicalSubstanceMonograph
pref label:
  en: Insulin Aspart (Genetical Recombination)
  ja: インスリン アスパルト(遺伝子組換え)
monograph id: JP18-insulin-aspart-genetical-recombination
publisher: JP
status: Official
version: 18
appearance:
  en: Insulin Aspart (Genetical Recombination) oc-curs as a white powder. It is practically insoluble in water and in ethanol (95). It dissolves in 0.01 mol/L hydrochloric acid TS. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Weigh a suitable amount of Insulin Aspart (Genetical Recombination), and dissolve in 0.01 mol/L hy-drochloric acid TS to make a solution so that each mL con-tains 2.0 mg. Separately, dissolve Insulin Aspart RS in 0.01 mol/L hydrochloric acid TS to make a solution so that each mL contains 2.0 mg. Transfer 25 mL each of these solutions into clean test tubes, add 100 mL of HEPES buffer solution (pH 7.5) and 20 mL of V8-protease TS, and allow to react at 259C for 6 hours. Then add 145 mL of ammonium sulfate buffer solution to stop the reaction, and use these solutions as the sample solution and the standard solution, respec-tively. Perform the test with exactly 50 mL each of the sam-ple solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi-tions, and compare the peak (peak 1) eluted just after the peak of the solvent and the succeeding three peaks (peaks 2, 3 and 4) with apparently higher peak height in the chromato-grams obtained from these solutions: the similar peaks are observed at the same retention times. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 214 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 10 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (not exceeding 5 mm in parti-cle diameter). Column temperature: A constant temperature of about 409C. Mobile phase A: A mixture of water, ammonium sulfate buffer solution and acetonitrile for liquid chromatography (7:2:1). Mobile phase B: A mixture of water, acetonitrile for liquid chromatography and ammonium sulfate buffer solution (2:2:1). Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) 0 – 60 90 → 30 10 → 70 60 – 65 30 → 0 70 → 100 65 – 70 Flow rate: 1 mL per minute. System suitability— System performance: When the proc…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Related substances—Perform the test with 10 mL of the sample solution obtained in the Assay as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method, and calculate the amounts of them by the area percentage method: the amount of the peak of B28isoAsp insulin aspart, having the relative retention time of about 0.9 to insulin aspart, is not more than 0.3z, the total amount of the peak of A21Asp insulin aspart and B3Asp insulin aspart, having the relative retention times of about 1.3, and the peak of B3isoAsp insulin aspart, having the relative retention time of about 1.5, is not more than 1.0z, and the total amount of the peaks other than the peaks mentioned above is not more than 0.5z. Operating conditions— Detector, column, column temperature, mobile phase A, mobile phase B, flowing of mobile phase and flow rate: Pro-ceed as directed in the operating conditions in the Assay. Time span of measurement: From 4 minutes to 50 minutes after injection of the sample solution. System suitability— System performance and system repeatability: Proceed as directed in the system suitability in the Assay. Test for required detectability: Pipet 5 mL of the solution for system suitability test obtained in the Assay, add 0.01 mol/L hydrochloric acid TS to make exactly 10 mL. Con-firm that the area percentage of the peak of B28isoAsp insu-lin aspart obtained with 10 mL of this solution is equivalent to 80 to 120z of that with 10 mL of the solution for system suitability test. High-molecular proteins—Store the sample solution at a temperature between 29C and 89C, and use within 48 hours after preparation. Dissolve 4 mg of Insulin Aspart (Genetical Recombination) in 1 mL of 0.01 mol/L hydro-chloric acid TS, and use this solution as the sample solution. Perform the test with 100 mL of the sample solution as di-rected under Liquid Chromatography <2.01> according to the following conditions, det…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Store the sample solution and the standard solution at a temperature between 29C and 89C, use the sample solu-tion within 24 hours after preparation, and use the standard solution within 48 hours after preparation. Weigh accurately a suitable amount of Insulin Aspart (Genetical Recombina-tion), dissolve in 0.01 mol/L hydrochloric acid TS so that each mL contains 4.0 mg, and use this solution as the sample solution. Separately, dissolve Insulin Aspart RS in 0.01 mol/L hydrochloric acid TS so that each mL contains 4.0 mg, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the total areas, AT and AS, of the peak of B28isoAsp insulin aspart (relative retention time to insulin aspart: about 0.9), the peak of insulin aspart (retention time: 20 to 24 minutes), the peak of A21Asp insulin aspart and B3Asp insulin aspart (usually eluted together having the relative retention time of about 1.3) and the peak of B3isoAsp insulin aspart (relative retention time: about 1.5) in each solution. Amount (mg) of insulin aspart (C256H381N65O79S6) ＝ MS × AT/AS MS: Total amount (mg) of insulin aspart, B28isoAsp insu-lin aspart, A21Asp insulin aspart and B3Asp insulin aspart, and B3isoAsp insulin aspart in 1 mL of the standard solution Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 214 nm). Column: A stainless steel column 4.0 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (not exceeding 5 mm in parti-cle diameter). Column temperature: A constant temperature of about 409C. 0 – 35 58 42 35 – 40 58 → 20 42 → 80 40 – 45 20 80 45 – 46 20 → 58 80 → 42 46 – 60 58 42 Flow rate: 1 mL per minute. System suitability— System performance: Dissolve Insulin Aspart (Genetical Recombination) in 0.01 mol/L sodium dihydrogen phos…
storage conditions:
  en: Containers—Tight containers. Storage—Not exceeding －189C.
type: PharmacopoeiaMonograph

insulin-glargine-genetical-recombination
type: BiologicalSubstanceMonograph
pref label:
  en: Insulin Glargine (Genetical Recombination)
  ja: インスリン グラルギン（遺伝子組換え）
monograph id: JP18-insulin-glargine-genetical-recombination
publisher: JP
status: Official
version: 18
definition:
  en: Insulin Glargine (Genetical Recombination) is a recombinant human insulin analogue, being substitut- JP XVIII Official Monographs / Insulin Glargine (Genetical Recombination) 1163 ed asparagine residue with glycine residue at 21st of A chain and added two arginine residues at C-terminal of B chain. It is a peptide composed with A chain consist-ing of 21 amino acid residues and B chain consisting of 32 amino acid residues. It contains not less than 94.
appearance:
  en: Insulin Glargine (Genetical Recombination) occurs as a white powder. It is practically insoluble in water and in ethanol (99.5). It is sparingly soluble in 0.01 mol/L hydrochloric acid TS. It is hygroscopic. It is gradually decomposed by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Keep the sample solution and standard solu-tion at 2 – 89C. Weigh a suitable amount of Insulin Glargine (Genetical Recombination) and Insulin Glargine RS, and dis-solve separately in 0.01 mol/L hydrochloric acid TS so that each mL contains 10.0 mg. Transfer 5 mL of these solutions into clean test tubes, add 1 mL of 1 mol/L tris buffer solu-tion (pH 7.5) and 100 mL of a solution of V8 protease for in-sulin glargine in 1 mol/L tris buffer solution (pH 7.5) (20 units/mL), allow to react at 35 – 379C for 3 hours, then add 2 mL of phosphoric acid to stop the reaction, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 50 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and compare the chromatograms obtained from these solutions: The similar peaks appear at the same reten-tion times. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 214 nm). Column: A stainless steel column 3 mm in inside diameter and 12.5 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (4 mm in particle diameter). Column temperature: A constant temperature of about 359C. Mobile phase A: To 930 mL of a solution, prepared by dissolving 11.6 g of phosphoric acid and 42.1 g of sodium perchloric acid in 1600 mL of water, adjusting to pH 2.3 with triethylamine and adding water to make 2000 mL, add 70 mL of acetonitrile for liquid chromatography. Mobile phase B: To 430 mL of a solution, prepared by dis-solving 11.6 g of phosphoric acid and 42.1 g of sodium per-chloric acid in 1600 mL of water, adjusting to pH 2.3 with triethylamine and adding water to make 2000 mL, add 570 mL of acetonitrile for liquid chromatography. Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as follows. appear next to the first peak just after the solvent peak, are not more than 1.5…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Related substances—Perform the test with 5 mL of the sample solution obtained in the Assay as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method, and calculate the amount of these peaks by the area percentage method: the amount of the peak other than insulin glargine is not more than 0.4z, and the total amount of the peaks other than insulin glargine is not more than 1.0z. Operating conditions— Detector, column, column temperature, mobile phases A and B, flowing of mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: For 40 minutes after injec-tion, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 1 mL of the sample solution, add 0.01 mol/L hydrochloric acid TS to make ex-actly 100 mL, and use this solution as the solution for system suitability test. Pipet 1 mL of the solution for system suitability test, add 0.01 mol/L hydrochloric acid TS to make exactly 10 mL. Confirm that the peak area of insulin glargine obtained with 5 mL of this solution is equivalent to 5 to 15z of that with 5 mL of the solution for system suitabil-ity test. System performance: When the procedure is run with 5 mL of the standard solution obtained in the Assay under the above operating conditions, the number of theoretical plates and the symmetry factor of the peak of insulin glargine are not less than 20,000 and not more than 1.8, respectively. System repeatability: When the test is repeated 6 times with 5 mL of the standard solution obtained in the Assay under the above operating conditions, the relative standard deviation of the peak area of insulin glargine is not more than 2.0z. High-molecular mass proteins—Keep the sample so-lution at 2 – 89C. Dissolve 15 mg of Insulin Glargine (Genet-ical Recombination) in 1.5 mL of 0.01 mol/L hydrochloric acid TS, add water to make 10 mL, and use …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Keep the sample solution and standard solution at 2 – 89C. Weigh accurately about 15 mg of Insulin Glargine (Genetical Recombination), dissolve in 1.5 mL of 0.01 mol/L hydrochloric acid TS, add water to make exactly 10 mL, and use this solution as the sample solution. Separately, dissolve Insulin Glargine RS in 0.01 mol/L hydrochloric acid TS so that each mL contains about 10 mg of insulin glargine, then exactly dilute with water so that each mL contains about 1.5 mg of insulin glargine, and use this solution as the standard solution. Perform the test with exactly 5 mL each of 0 – 20 96 → 83 4 → 17 20 – 30 83 → 63 17 → 37 30 – 40 63 → 96 37 → 4 Flow rate: 0.55 mL per minute (the retention time of insu-lin glargine is about 21 minutes). System suitability— System performance: When the procedure is run with 5 mL of the standard solution under the above operating condi-tions, the number of theoretical plates and the symmetry fac-tor of the peak of insulin glargine are not less than 20,000 and not more than 1.8, respectively. System repeatability: When the test is repeated 6 times with 5 mL of the standard solution under the above operating conditions, the relative standard deviation of the peak area of insulin glargine is not more than 2.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Not exceeding －159C.
type: PharmacopoeiaMonograph

insulin-human
type: BiologicalSubstanceMonograph
pref label:
  en: Insulin Human
  ja: インスリン ヒト（遺伝子組換え）
monograph id: JP18-insulin-human
publisher: JP
status: Official
version: 18
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

interferon-alfa-namalwa
type: BiologicalSubstanceMonograph
pref label:
  en: Interferon Alfa (NAMALWA)
  ja: インターフェロン アルファ(NAMALWA)
monograph id: JP18-interferon-alfa-namalwa
publisher: JP
status: Official
version: 18
definition:
  en: Interferon Alfa (NAMALWA) is essentially a hu-man interferon alfa, which is a glycoprotein (molecu-lar mass: 17,000 – 30,000) produced by the human lymphoblast NAMALWA cell induced by Sendai vi-rus. It is an aqueous solution. It possesses the antiviral activity. It contains not less than 50 mg and not more than 500 mg of protein per mL, and not less than 1.
appearance:
  en: Interferon Alfa (NAMALWA) occurs as a clear and colorless liquid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To Interferon Alfa (NAMALWA) add Eagle's minimum essential medium containing bovine serum so that each mL contains 5000 Units, and use this solution as the sample stock solution. To anti-interferon alfa antiserum add an amount of Eagle's minimum essential medium con-taining bovine serum so that each mL contains an amount of anti-interferon alfa antiserum which neutralizes 10,000 Units of interferon alfa. To this solution add an equal volume of the sample stock solution, stir, and use this solution as the sample solution. Separately, to the sample stock solution add an equal volume of Eagle's minimum essential medium containing bovine serum, stir, and use this solution as the control solution. Determine the remained potency of the sample solution and control solution after allowing to stand at 37 ± 19C for 1 hour, according to the Assay. When the antiviral activity of Interferon Alfa (NAMALWA) is neu-tralized by anti-interferon alfa antiserum, it meets the requirement. Not detection of the remaining potency of the sample solution is a criterion of neutralization. (2) Soak polyvinylidene fluoride membrane in methanol for 10 – 20 seconds, then soak additionally in phosphate-buffered sodium chloride TS for more than 30 minutes. To the well in the dot blot apparatus mounted the polyvinyli- dene fluoride membrane, add a volume of Interferon Alfa (NAMALWA), corresponding to about 20 mg protein, allow to stand for 15 minutes, and aspirate. After repeating twice to aspirate with a 0.2-mL portion of phosphate-buffered so-dium chloride TS, take out the polyvinylidene fluoride mem-brane, soak in 0.01 mol/L tris buffer solution-sodium chlo-ride TS (pH 7.4), and stir gently for 10 minutes. Replace the liquid, and repeat this operation two more times. Remove 0.01 mol/L tris buffer solution-sodium chloride TS (pH 7.4), add elderberry lectin TS, and stir gently for 2 hours. Remove the elderberry lectin TS, add 0.01 mol/L tris buffer solution-sodium chloride TS (pH 7.4), and stir…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Egg albumin, Sendai virus coat protein, other foreign proteins, and other process-related impurities—Being specified separately when the drug is granted approval based on the Law. Nucleic acids—Perform the test according to the fol-lowing method: the amount of nucleic acids is not more than 1.0 pg as DNA per 1,000,000 Units of interferon alfa (NAMALWA). DNA standard solutions: To the DNA standard stock solution for interferon alfa (NAMALWA) add salmon sperm DNA solution (1 in 10,000,000) so that each mL con-tains exactly 20 ng DNA. Hereinafter, the concentration of Phthalaldehyde in ethanol (99.5) solution (2 in 25) — — 10 mL DNA is the concentration of DNA for interferon alfa Lauromacrogol solution (1 in 4) — — 4 mL 2-Mercaptoethanol — — 2 mL 10z Sodium hypochlorite TS — 0.1 mL — (NAMALWA). To this solution add tris-glycine buffer solu- tion (pH 6.8) exactly so that each mL contains 10 ng DNA. Then, dilute serially by adding tris-glycine buffer solution Water a suitable quantity a suitable quantity a suitable quantity (pH 6.8). Dilute exactly with a mixture of tris-glycine buffer solution (pH 6.8) and 1 mol/L tris buffer solution (pH 8.0) Total amount 1000 mL 1000 mL 1000 mL Flow rate of mobile phase: Adjust so that the retention times of aspartic acid, glutamic acid and methionine are about 12, 20 and 42 minutes, respectively. Flow rate of reaction reagent: About 0.2 mL per minute for each of reagent A, B, and C. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the resolutions between the peaks of threonine and serine, glycine and alanine, and isoleucine and leucine are not less than 0.6, not less than 0.8 and not less than 1.2, re-spectively. System repeatability: When the test is repeated 3 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviations of the peak area of aspartic acid, proline, valine, and arginine a…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Protein content— Sample solution: Dilute Interferon Alfa (NAMAL-WA) with isotonic sodium chloride solution so that each mL contains 3,000,000 to 4,000,000 Units, and use this solution as the sample solution. 1 cm Standard solution: Weigh accurately about 50 mg of bovine serum albumin, and dissolve in isotonic sodium chlo-ride solution to make exactly 50 mL. Determine the absor-bance of this solution at 280 nm as directed under Ultravio-let-visible Spectrophotometry <2.24>. Calculate the protein concentration based on E1z (280 nm) ＝ 6.6. To this solu-tion add isotonic sodium chloride solution so that each mL contains exactly 50, 25, 12.5, 6.25, and 3.13 mg of the bovine serum albumin, and use these solutions as the standard solu-tions. Procedure: To exactly 0.25 mL each of the sample solution and the standard solutions add exactly 0.25 mL of Coomassie brilliant blue TS for interferon alfa, and allow to stand at room temperature for exactly 30 seconds. Determine the absorbance of these solutions at 614 nm as directed under Ultraviolet-visible Spectrophotometry <2.24> using water as the blank. Plot the absorbance of the standard solu-tions on the vertical axis and their protein concentrations on the horizontal axis to prepare a calibration curve. Determine the protein content of the sample solution from its absorbance using the calibration curve, and calculate the amount of protein per mL of the sample solution. Perform a blank determination in the same manner with isotonic so-dium chloride solution, and make any necessary correction. (2) Specific activity—To each well of a flat-bottom microplate add 45,000 to 60,000 cells of FL cell, prepared with Eagle's minimum essential medium containing bovine serum, and incubate at 37 ± 19C for 18 to 22 hours in an in-cubator filled with 5z carbon dioxide. Dilute Interferon Alfa (NAMALWA) and Interferon Alfa RS separately with Eagle's minimum essential medium containing bovine serum so that each mL contains about 30 Units, an…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

pancreatin
type: BiologicalSubstanceMonograph
pref label:
  en: Pancreatin
  ja: パンクレアチン
monograph id: JP18-pancreatin
publisher: JP
status: Official
version: 18
definition:
  en: Pancreatin is a substance containing enzymes pre-pared from the pancreas of edible animals, mostly the hog, and has amylolytic, proteolytic and lipolytic ac-tivities. It contains not less than 2800 starch saccharifying activity units, not less than 28,000 proteolytic activity units, and not less than 960 lipolytic activity units per g.
appearance:
  en: Pancreatin occurs as a white to light yellow powder. It has a characteristic odor.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Rancidity—Pancreatin has no unpleasant or rancid odor and is tasteless. Fat—Add 20 mL of diethyl ether to 1.0 g of Pancrea-tin, extract with occasional shaking for 30 minutes, and filter. Wash the residue with 10 mL of diethyl ether, combine the washing with the filtrate, evaporate the diethyl ether, and dry the residue at 1059C for 2 hours: the mass of the residue does not exceed 20 mg. Loss on drying <2.41> Not more than 4.0z (1 g, in vacu-um, phosphorus (V) oxide, 24 hours). Residue on ignition <2.44> Not more than 5z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Starch digestive activity <4.03> Substrate solution—Use potato starch TS for amylo-lytic activity test, prepared by adding 10 mL of phosphate buffer solution for pancreatin instead of 10 mL of 1 mol/L acetic acid-sodium acetate buffer solution (pH 5.0). Sample solution—Weigh accurately about 0.1 g of Pancreatin, add a suitable amount of ice-cold water, stir, and add ice-cold water to make exactly 100 mL. Pipet 10 mL of this solution, and add ice-cold water to make exactly 100 mL. Procedure—Proceed as directed in 1.1. Measure-ment of starch saccharifying activity of 1. Assay for starch digestive activity under Digestion Test. Protein digestive activity <4.03> Substrate solution—Use the substrate solution 2 described in 2.3. (ii) of 2. Assay for protein digestive activity under Digestion Test after adjusting the pH to 8.5. Sample solution—Weigh accurately about 0.1 g of Pancreatin, add a suitable amount of ice-cold water, stir, and add ice-cold water to make exactly 200 mL. Procedure—Proceed as directed in 2. Assay for pro-tein digestive activity under Digestion Test, using trichloroa-cetic acid TS B as the precipitation reagent. Fat digestive activity <4.03> Emulsifier—Prepare with 18 g of polyvinyl alcohol I and 2 g of polyvinyl alcohol II as directed in 3. Assay for fat digestive activity under Digestion Test. Substrate solution—Use the substrate solution Amount (mg) of ozagrel sodium (C H N NaO ) described in 3. Assay for fat digestive activity under the ＝ MS × QT/QS × 16 13 11 2 2 Digestion Test. Sample solution—Weigh accurately about 0.1 g of MS: Amount (mg) of Ozagrel Sodium RS taken Internal standard solution—A solution of benzoic acid in methanol (1 in 100).
storage conditions:
  en: Containers—Hermetic containers.

pepsin
type: EnzymePreparationMonograph
pref label:
  en: Pepsin
  ja: ペプシン
alt label: Pepsin A
alt label: Gastric Protease
monograph id: JP18-0319
publisher: JP
status: Official
effective date: 2021-06-25
version: 18
definition:
  en: Pepsin is a proteolytic enzyme obtained from the gastric mucosa of the pig, Sus scrofa Linné var. domesticus Gray (Suidae), or of the cow, Bos taurus Linné var. domesticus Gmelin (Bovidae), or from the gastric juice of the hog, having not less than 3000 Units per g when determined as directed in the Assay.
biological source type: Enzyme
biological origin:
  en: Gastric mucosa of pig (Sus scrofa domesticus) or cow (Bos taurus), or gastric juice of hog
source organism:
  en: Sus scrofa Linné var. domesticus Gray (Suidae) or Bos taurus Linné var. domesticus Gmelin (Bovidae)
enzyme commission number: EC 3.4.23.1
enzyme activity:
  en: Not less than 3000 Units per g
optimal PH:
  en: pH 1.5-2.5
optimal temperature:
  en: 37-42°C
activity unit:
  en: One unit of pepsin activity is the amount of enzyme which liberates 1 μmol of tyrosine per minute at 37°C and pH 1.7 using hemoglobin as substrate
appearance:
  en: White to light yellow powder or flakes, having a characteristic, slightly acid odor
solubility:
  en: Soluble in water, practically insoluble in ethanol (95) and in diethyl ether. The solution in water is usually slightly turbid.
test specification: IdentificationSpecification
  test name:
    en: Identification A - Digestion Test
  test type: TestType-Identification
  test conditions:
    en: Place 10 mL of a solution of egg white in a test tube, add 2 mL of dilute hydrochloric acid and 0.1 g of Pepsin, and keep at 38-40°C: the mixture becomes turbid, then gradually clarifies.
test specification: IdentificationSpecification
  test name:
    en: Identification B - Protein Test
  test type: TestType-Identification
  test conditions:
    en: To 5 mL of a solution of Pepsin (1 in 100) add 2 mL of ninhydrin TS, and heat: a blue-purple color is produced.
test specification: PHSpecification
  test name:
    en: pH
  test type: TestType-Physical
  harmonized method: pH
  ph range: 3.5-5.5
  solution conditions:
    en: The pH of a solution (1 in 100)
test specification: PuritySpecification
  test name:
    en: Clarity and Color of Solution
  test type: TestType-Purity
  test conditions:
    en: Dissolve 0.5 g of Pepsin in 10 mL of water: the solution is slightly turbid and light yellow to yellow-brown in color.
test specification: PuritySpecification
  test name:
    en: Dry Products
  test type: TestType-Purity
  test conditions:
    en: To 0.5 g of Pepsin add 10 mL of water, shake well, filter, and to the filtrate add 2 drops of dilute acetic acid: no precipitate is formed.
test specification: PuritySpecification
  test name:
    en: Fat
  test type: TestType-Purity
  test conditions:
    en: Place 1.0 g of Pepsin in a glass-stoppered bottle, add 30 mL of petroleum ether, shake for 15 minutes, and filter through a dry filter paper. Evaporate 10 mL of the filtrate on a water bath, and dry the residue at 105°C for 2 hours: the mass of the residue is not more than 10 mg.
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 3.0
    limit unit: percent
test specification: PuritySpecification
  test name:
    en: Heavy Metals
  test type: TestType-Purity
  harmonized method: HeavyMetals-Method2
  impurity type:
    en: Heavy Metals as Pb
  test conditions:
    en: Proceed according to Method 2 using 1.0 g of Pepsin. Prepare the control solution with 3.0 mL of Standard Lead Solution.
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 30
    limit unit: ppm
test specification: PuritySpecification
  test name:
    en: Arsenic
  test type: TestType-Purity
  harmonized method: Arsenic-Method1
  impurity type:
    en: Arsenic
  test conditions:
    en: Prepare the test solution with 1.0 g of Pepsin according to Method 1, and perform the test.
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 2
    limit unit: ppm
test specification: LossOnDryingSpecification
  test name:
    en: Loss on Drying
  test type: TestType-Physical
  harmonized method: LossOnDrying
  drying conditions:
    en: Dry 0.5 g of Pepsin at 105°C for 4 hours
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 5.0
    limit unit: percent
test specification: ResidueOnIgnitionSpecification
  test name:
    en: Residue on Ignition
  test type: TestType-Physical
  harmonized method: ResidueOnIgnition
  ignition conditions:
    en: Proceed as directed under Residue on Ignition Test, using 0.5 g of Pepsin
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 5.0
    limit unit: percent
test specification: AssaySpecification
  test name:
    en: Assay (Pepsin Activity)
  test type: TestType-Assay
  assay target:
    en: Pepsin Activity (Units per g)
  test conditions:
    en: Weigh accurately about 0.05 g of Pepsin, dissolve in dilute hydrochloric acid (1 in 100) to make exactly 50 mL, and use this solution as the sample solution. Separately, dissolve 0.05 g of hemoglobin in 5 mL of water, add 10 mL of 0.1 mol/L hydrochloric acid TS, and add water to make exactly 50 mL. Pipet 5 mL of this solution, warm to 37°C, add exactly 1 mL of the sample solution previously warmed to 37°C, shake immediately, and allow to stand at 37°C for exactly 10 minutes. Then add exactly 10 mL of trichloroacetic acid TS, shake, allow to stand for 30 minutes, and filter through a dry filter paper. Discard the first 5 mL of the filtrate, and use the subsequent filtrate as the test solution. Prepare a blank solution in the same manner, but add 1 mL of dilute hydrochloric acid (1 in 100) instead of the sample solution. Determine the absorbance of the test solution at 275 nm, taking the blank solution as the blank. Calculate the activity using the formula: Activity (Units/g) = (A × 50 × V) / (W × 1.05 × 10), where A is the absorbance of the test solution, V is the dilution factor of the sample solution, and W is the mass (g) of the sample.
  limit: Limit
    limit type: LimitType-NotLessThan
    limit value: 3000
    limit unit: Units/g
storage container:
  en: Tight containers, protected from light
storage conditions:
  en: Store in a cool place, protect from moisture

saccharated-pepsin
type: BiologicalSubstanceMonograph
pref label:
  en: Saccharated Pepsin
  ja: 含糖ペプシン
monograph id: JP18-saccharated-pepsin
publisher: JP
status: Official
version: 18
definition:
  en: Saccharated Pepsin is a mixture of pepsin obtained from the gastric mucosa of hog or cattle and Lactose Hydrate, and it is an enzyme drug having a proteolytic activity. It contains not less than 3800 units and not more ‌than 6000 units per g.
appearance:
  en: Saccharated Pepsin occurs as a white powder. It has a characteristic odor, and has a slightly sweet taste. It dissolves in water to give a slightly turbid liquid, and does not dissolve in ethanol (95) and in diethyl ether. It is slightly hygroscopic.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Rancidity—Saccharated Pepsin has no un-pleasant or rancid odor. (2) Acidity—Dissolve 0.5 g of Saccharated Pepsin in 50 mL of water, and add 0.50 mL of 0.1 mol/L sodium hydrox-ide VS and 2 drops of phenolphthalein TS: the solution is red in color. Loss on drying <2.41> Not more than 1.0z (1 g, 809C, 4 hours). Residue on ignition <2.44> Not more than 0.5z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (i) Substrate solution—Use the substrate solution 1 described in Assay for protein digestive activity under Diges-tion Test <4.03> after adjusting the pH to 2.0. Sample solution—Weigh accurately an amount of Saccharated Pepsin equivalent to about 1250 units, dissolve in ice-cold 0.01 mol/L hydrochloric acid TS to make exactly 50 ml. Standard solution—Weigh accurately a suitable amount of Saccharated Pepsin RS, and dissolve in ice-cold 0.01 mol/L hydrochloric acid TS to make a solution contain-ing about 25 units per mL. Procedure—Proceed as directed in Assay for protein digestive activity under Digestion Test <4.03>, and determine the absorbances, AT and ATB, of the sample solution, using trichloroacetic acid TS A as the precipitation reagent. Sepa-rately, determine the absorbances, AS and ASB, of the stand-ard solution in the same manner as the sample solution. Units in 1 g of Saccharated Pepsin ＝ US × (AT － ATB)/(AS － ASB) × 1/M US: Units per mL of the standard solution M: Amount (g) of Saccharated Pepsin per mL of the sam-ple solution taken
storage conditions:
  en: Containers—Tight containers. Storage—Not exceeding 309C.

whole-human-blood
type: BiologicalSubstanceMonograph
pref label:
  en: Whole Human Blood
  ja: 人全血液
monograph id: JP18-whole-human-blood
publisher: JP
status: Official
version: 18
appearance:
  en: Whole Human Blood is a deep red liquid from which the erythrocytes settle upon standing, leaving a yellow supernatant layer. A gray layer which mainly consists of leu-cocytes may appear on the surface of the settled erythrocyte layer. The supernatant layer may become turbid in the presence of fat, or may show the faint color of hemoglobin. Wine

https://www.openphar.org/data/jp/chemicals/-15--0841
type: ChemicalDrugMonograph
pref label:
  en: × 1/5 × 0.841
  ja: ホミカエキス散
monograph id: JP18--15--0841
publisher: JP
status: Official
version: 18
appearance:
  en: Nux Vomica Extract Powder occurs as a yel-low-brown to grayish brown powder. It has a slight, charac-teristic odor and a bitter taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 3 g of Nux Vomica Extract Powder add 3 mL of ammonia TS and 20 mL of chloroform, macer-ate for 30 minutes with occasional shaking, and filter. Re-move most of the chloroform from the filtrate by warming on a water bath, add 5 mL of diluted sulfuric acid (1 in 10), and warm on a water bath while shaking well until the odor of chloroform is no longer perceptible. After cooling, filter through a pledget of absorbent cotton, and add 2 mL of nitric acid to 1 mL of the filtrate: a red color develops. (2) To the remaining filtrate obtained in (1) add 1 mL of potassium dichromate TS, and allow to stand for 1 hour: a yellow-red precipitate is produced. Collect the precipitate by filtration, and wash with 1 mL of water. Transfer a part of the precipitate to a small test tube, add 1 mL of water, dis-solve by warming, cool, and add 5 drops of sulfuric acid dropwise carefully along the wall of the test tube: the layer of sulfuric acid shows a purple color which turns immedi-ately red to red-brown.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 2.0 g of Nux Vomica Ex-tract Powder, place in a glass-stoppered centrifuge tube, add 15 mL of ammonia TS, and shake. Add 20 mL of diethyl ether, stopper tightly, shake for 15 minutes, centrifuge to separate the diethyl ether layer. To the aqueous layer add 20 mL of diethyl ether, proceed in the same manner, and repeat this procedure three times. Combine the extracts, and evapo-rate the solvent on a water bath. Dissolve the residue in 10 mL of the mobile phase, add exactly 10 mL of the internal standard solution, and add the mobile phase to make 100 mL. Filter this solution through a membrane filter with a porosity not more than 0.8 mm, discard the first 2 mL of the filtrate, and use the subsequent filtrate as the sample solu-tion. Separately, weigh accurately about 75 mg of strychnine nitrate for assay (separately determine the loss on drying), and dissolve in the mobile phase to make exactly 50 mL. Pipet 10 mL of this solution, add exactly 10 mL of the inter-nal standard solution, then add the mobile phase to make 100 mL, and use this solution as the standard solution. Per-form the test with exactly 5 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions. Calcu-late the ratio, QT and QS, of the peak area of strychnine to MS: Amount (mg) of strychnine nitrate for assay taken, calculated on the dried basis Internal standard solution—A solution of barbital sodium in the mobile phase (1 in 500). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm). Column: A stainless steel column about 4 mm in inside diameter and about 15 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: Room temperature. Mobile phase: A mixture of a solution of potassium dihy-drogenphosphate (6.8 in 1000), acetonitrile and triethyla-mine (45:5:1), adjusted the pH to 3.0 with …
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

acebutolol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Acebutolol Hydrochloride
  ja: アセブトロール塩酸塩
monograph id: JP18-acebutolol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C18H28N2O4.HCl
molecular weight: 372.89
cas number: 34381-68-5
definition:
  en: Acebutolol Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Acebutolol Hydrochloride occurs as white to pale yellow-white, crystals or crystalline powder. It is freely soluble in water, in methanol, in ethanol (95) and in acetic acid (100), and practically insoluble in diethyl ether. A solution of Acebutolol Hydrochloride (1 in 20) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Acebutolol Hydrochloride in 0.01 mol/L hydro-chloric acid TS (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Acebutolol Hydrochloride, previously dried, as directed in the potassium bromide disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Acebutolol Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Acebutolol Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Acebutolol Hydrochloride according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 40 mg of Acebutolol Hydrochloride in 2 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 25 mL, and pipet 1 mL of this so-lution, add methanol to make exactly 20 mL, and use this so-lution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatogra-phy. Develop the plate with the upper layer of a mixture of water, 1-butanol and acetic acid (100) (5:4:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultravio-let light (main wavelength: 365 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 1.0z (0.5 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of Acebutolol Hydro-chloride, previously dried, dissolve in 20 mL of acetic acid (100), add 80 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 37.29 mg of C18H28N2O4.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

acemetacin
type: ChemicalDrugMonograph
pref label:
  en: Acemetacin
  ja: アセメタシン
monograph id: JP18-acemetacin
publisher: JP
status: Official
version: 18
molecular formula: C21H18ClNO6
molecular weight: 415.82
cas number: 53164-05-9
definition:
  en: Acemetacin, when dried, contains not less than 99.
appearance:
  en: Acemetacin occurs as a light yellow crystalline powder. It is soluble in acetone, sparingly soluble in methanol, slightly soluble in ethanol (99.5), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mg of Acemetacin add 1 mL of concentrated chromotropic acid TS, and heat in a water bath for 5 minutes: a red-purple color develops. Determine the absorption spectrum of a solution of Acemetacin in methanol (1 in 50,000) as directed under Ul-traviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Acemetacin as directed in the potassium bromide disk method under Infrared Spectrometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave ‌400 numbers. Perform the test with Acemetacin as directed under Flame Coloration Test <1.04> (2): a green color appears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Acemetacin according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 0.40 g of Acemetacin in 10 mL of acetone, and use this solution as the sample so-lution. Pipet 1 mL of the sample solution, and add acetone to make exactly 50 mL. Pipet 1 mL of this solution, add ace-tone to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin Layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin layer chromatography. Develop the plate with a mixture of hexane, 4-methyl-2-pentanone and acetic acid (100) (3:2:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the num-ber of spots other than the principal spot obtained from the sample solution is not more than 2, and these spots are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.35 g of Acemetacin, previ-ously dried, dissolve in 20 mL of acetone, add 10 mL of water, and then titrate <2.50> with 0.1 mol/L sodium hy-droxide VS (potentiometric titration). Perform a blank de-termination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS (main wavelength: 254 nm): the spots obtained from the sample solution and standard solution show the same Rf value. Uniformity of dosage units <6.02> Perform the test accord-ing to the following method: it meets the requirement of the Content uniformity test. Take out the contents of 1 capsule of Acemetacin Cap-sules, add 40 mL of methanol, shake well, and add methanol to make exactly V mL so that each mL contains about 0.6 mg of acemetacin (C21H18ClNO6). Filter this solution, dis-card the first 10 mL of the filtrate, pipet 5 mL of the subse-quent filtrate, add exactly 2 mL of the internal standard so-lution, add methanol to make 50 mL, and use this solution as the sample solution. Proceed as directed in the Assay. Amount (mg) of acemetacin (C21H18ClNO6) ＝ MS × QT/QS × V/50 MS: Amount (mg) of acemetacin for assay taken Internal standard solution—A solution of hexyl parahy-droxybenzoate in methanol (1 in 1000). Dissolution <6.10> When the test is performed at 50 revolu-tions per minute according to the Paddle method using the sinker, using 900 mL of 2nd fluid for dissolution test as the dissolution medium, the dissolution rate in 30 minutes of Acemetacin Capsules is not less than 70z. Start the test with 1 capsule of Acemetacin Capsules, with-draw not less than 20 mL of the medium at the specified minute after starting the test, and filter through a membrane filter with a pore size not exceeding 0.45 mm. Discard not less than 10 mL of the first filtrate, pipet V mL of the subsequent filtrate, add the dissolution medium to make exactly V? mL so that each mL contains about 33 mg of acemetacin (C21H18ClNO6), and use this solution as the sample so…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

acetaminophen
type: ChemicalDrugMonograph
pref label:
  en: Acetaminophen
  ja: アセトアミノフェン
alt label: Paracetamol
alt label: N-Acetyl-p-aminophenol
alt label: APAP
monograph id: JP18-0099
publisher: JP
status: Official
effective date: 2021-06-25
version: 18
definition:
  en: Acetaminophen, when dried, contains not less than 98.0% of C8H9NO2.
molecular formula: C8H9NO2
molecular weight: 151.16
cas number: 103-90-2
systematic name:
  en: N-(4-Hydroxyphenyl)acetamide
inchi: InChI=1S/C8H9NO2/c1-6(10)9-7-2-4-8(11)5-3-7/h2-5,11H,1H3,(H,9,10)
inchi key: RZVAJINKPMORJF-UHFFFAOYSA-N
smiles: CC(=O)NC1=CC=C(C=C1)O
chemical structure: https://pubchem.ncbi.nlm.nih.gov/image/imgsrv.fcgi
appearance:
  en: White crystals or crystalline powder, odorless, slightly bitter taste
solubility:
  en: Freely soluble in ethanol (95), sparingly soluble in water, slightly soluble in diethyl ether. Dissolves in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification A - IR
  test type: TestType-Identification
  harmonized method: IR
  test conditions:
    en: Determine the infrared absorption spectrum of the sample as directed in the potassium bromide disk method under Infrared Spectrophotometry, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
  reference spectrum: acetaminophen
test specification: IdentificationSpecification
  test name:
    en: Identification B - Chemical
  test type: TestType-Identification
  test conditions:
    en: To 0.1 g of Acetaminophen add 10 mL of dilute hydrochloric acid, boil for 1 minute, cool, add 1 drop of sodium nitrite TS, allow to stand for 2 minutes, then add 2 mL of ammonium sulfamate TS, mix, and allow to stand for 10 minutes. Add 2 mL of N-(1-naphthyl)-N'-diethyl ethylenediamine oxalate TS: a red-purple color develops.
test specification: MeltingPointSpecification
  test name:
    en: Melting Point
  test type: TestType-Physical
  harmonized method: MeltingPoint
  melting point range: 169-172
  temperature unit: Celsius
test specification: PuritySpecification
  test name:
    en: Clarity and Color of Solution
  test type: TestType-Purity
  test conditions:
    en: Dissolve 1.0 g of Acetaminophen in 20 mL of ethanol (95): the solution is clear and colorless to pale yellow.
test specification: PuritySpecification
  test name:
    en: Related Substances
  test type: TestType-Purity
  harmonized method: HPLC-UV
  impurity type:
    en: p-Aminophenol and other related substances
  test conditions:
    en: Dissolve 0.10 g of Acetaminophen in 10 mL of a mixture of water and methanol (1:1), and use this solution as the sample solution. Perform the test with 10 μL of this solution as directed under Liquid Chromatography according to the following conditions. Determine each peak area by the automatic integration method: the area of the peak appearing at the retention time of p-aminophenol is not more than 0.05% of the peak area of acetaminophen, and the area of any peak other than acetaminophen and p-aminophenol is not more than 0.1% of the peak area of acetaminophen.
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 0.05
    limit unit: percent
test specification: PuritySpecification
  test name:
    en: Heavy Metals
  test type: TestType-Purity
  harmonized method: HeavyMetals-Method1
  impurity type:
    en: Heavy Metals as Pb
  test conditions:
    en: Proceed according to Method 1 using 2.0 g of Acetaminophen. Prepare the control solution with 2.0 mL of Standard Lead Solution (for the test, use a quartz or porcelain crucible).
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 10
    limit unit: ppm
test specification: PuritySpecification
  test name:
    en: Arsenic
  test type: TestType-Purity
  harmonized method: Arsenic-Method1
  impurity type:
    en: Arsenic
  test conditions:
    en: Prepare the test solution with 1.0 g of Acetaminophen according to Method 1, and perform the test (not more than 2 ppm).
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 2
    limit unit: ppm
test specification: PuritySpecification
  test name:
    en: p-Chloroacetanilide
  test type: TestType-Purity
  harmonized method: GC
  impurity type:
    en: p-Chloroacetanilide
  test conditions:
    en: Weigh accurately about 0.5 g of Acetaminophen, add exactly 5 mL of the internal standard solution, and dissolve by warming if necessary. Cool, and use this solution as the sample solution. Separately, weigh accurately about 10 mg of p-Chloroacetanilide for thin-layer chromatography, add methanol to make exactly 100 mL. Pipet 1 mL of this solution, add exactly 5 mL of the internal standard solution, and use this solution as the standard solution. Perform the test with 1 μL each of the sample solution and standard solution as directed under Gas Chromatography according to the following conditions. Calculate the ratios of the peak area of p-chloroacetanilide to that of the internal standard from the sample solution and the standard solution.
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 0.001
    limit unit: percent
test specification: LossOnDryingSpecification
  test name:
    en: Loss on Drying
  test type: TestType-Physical
  harmonized method: LossOnDrying
  drying conditions:
    en: Dry at 105°C for 2 hours
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 0.5
    limit unit: percent
test specification: ResidueOnIgnitionSpecification
  test name:
    en: Residue on Ignition
  test type: TestType-Physical
  harmonized method: ResidueOnIgnition
  ignition conditions:
    en: Proceed as directed under Residue on Ignition Test
  limit: Limit
    limit type: LimitType-NotMoreThan
    limit value: 0.1
    limit unit: percent
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  harmonized method: Titrimetric-Neutralization
  assay target:
    en: Acetaminophen (C8H9NO2)
  assay expression: on dried basis
  test conditions:
    en: Weigh accurately about 0.3 g of Acetaminophen, previously dried, add 40 mL of water and 40 mL of hydrochloric acid, and dissolve by heating. After cooling, add 0.2 g of potassium bromide, titrate with 0.1 mol/L sodium nitrite VS (potentiometric titration) while cooling the solution in ice water and stirring. Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium nitrite VS = 15.12 mg of C8H9NO2.
  limit: Limit
    limit type: LimitType-NotLessThan
    limit value: 98.0
    limit unit: percent
storage container:
  en: Well-closed containers
storage conditions:
  en: Store at room temperature

acetazolamide
type: ChemicalDrugMonograph
pref label:
  en: Acetazolamide
  ja: アセタゾラミド
monograph id: JP18-acetazolamide
publisher: JP
status: Official
version: 18
molecular formula: C4H6N4O3S2
molecular weight: 222.25
definition:
  en: Acetazolamide contains not less than 98.
appearance:
  en: Acetazolamide occurs as a white to pale yellow-white crystalline powder. It is odorless, and has a slight bitter taste. It is slightly soluble in ethanol (95), very slightly soluble in water, and practically insoluble in diethyl ether. Melting point: about 2559C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 0.1 g of Acetazolamide add 5 mL of sodium hydroxide TS, then add 5 mL of a solution of 0.1 g Chloride <1.03>—To 1.5 g of Acetazolamide add 75 mL of water, and warm at 709C for 20 minutes with occa-sional shaking. After cooling, filter, and to 25 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.20 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.014z). Sulfate <1.14>—To 25 mL of the filtrate obtained in (2) add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solu-tion. Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not more than 0.038z). Heavy metals <1.07>—Proceed with 1.0 g of Aceta- zolamide according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Silver-reducing substances—Wet 5 g of Acetazola-mide with 5 mL of aldehyde-free ethanol, and add 125 mL of water, 10 mL of nitric acid and exactly 5 mL of 0.1 mol/L silver nitrate VS. Stir for 30 minutes by protecting from light, filter through a glass filter (G3), and wash the residue on the glass filter with two 10-mL portions of water. Com-bine the filtrate with the washings, to the solution add 5 mL of ammonium iron (III) sulfate TS, and titrate <2.50> with 0.1 mol/L ammonium thiocyanate VS: not less than 4.8 mL of 0.1 mol/L ammonium thiocyanate VS is consumed. Loss on drying <2.41> Not more than 0.5z (0.5 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (0.5 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of Acetazolamide, and dissolve in 400 mL of water in a water bath by heating. After cooling, add water to make exactly 1000 mL. Pipet 5 mL of the solution, add 10 mL of 1 mol/L hydrochloric acid TS, and then add water to make exactly 100 mL. Determine the absorbance A of this solution at the wavelength of maxi-mum absorption at about 265 nm as directed under Ultravio-let-visible Spectrophotometry <2.24>. Amount (mg) of acetazolamide (C4H6N4O3S2) ＝ A/474 × 200,000
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

acetic-acid
type: ChemicalDrugMonograph
pref label:
  en: Acetic Acid
  ja: 酢酸
monograph id: JP18-acetic-acid
publisher: JP
status: Official
version: 18
definition:
  en: Acetic Acid contains not less than 30.
appearance:
  en: Acetic Acid is a clear, colorless liquid. It has a pungent, characteristic odor and an acid taste. It is miscible with water, with ethanol (95) and with glycerin. Specific gravity d 20: about 1.04
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Acetic Acid changes blue litmus paper to red, and responds to Qualitative Tests <1.09> for acetate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Acetazolamide in 10 mL of sodium hydroxide TS: the solution is clear and colorless to pale yellow. Description Acetic Acid is a clear, colorless liquid. It has a pungent, characteristic odor and an acid taste. It is miscible with water, with ethanol (95) and with glycerin. Specific gravity d 20: about 1.04 Identification Acetic Acid changes blue litmus paper to red, and responds to Qualitative Tests <1.09> for acetate. Purity (1) Chloride—To 20 mL of Acetic Acid add 40 mL of water, and use this solution as the sample solution. To 10 mL of the sample solution add 5 drops of silver nitrate TS: no opalescence is produced. ‌404‌ Sulfate—To 10 mL of the sample solution obtained in (1) add 1 mL of barium chloride TS: no turbidity is pro-duced. Heavy metals <1.07>—Evaporate 10 mL of Acetic Acid on a water bath to dryness, and to the residue add 2 mL of dilute acetic acid and water to make 50 mL. Perform the test with this solution as the test solution. Prepare the con-trol solution with 3.0 mL of Standard Lead Solution by add-ing 2 mL of dilute acetic acid and water to make 50 mL (not more than 3 ppm). Potassium permanganate-reducing substances—To 20 mL of the sample solution obtained in (1) add 0.10 mL of 0.02 mol/L potassium permanganate VS: the red color does not disappear within 30 minutes. Non-volatile residue—Evaporate 30 mL of Acetic Acid on a water bath to dryness, and dry at 1059C for 1 hour: the mass of the residue is not more than 1.0 mg.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Measure exactly 5 mL of Acetic Acid, add 30 mL of water, and titrate <2.50> with 1 mol/L sodium hydroxide VS (indicator: 2 drops of phenolphthalein TS). Each mL of 1 mol/L sodium hydroxide VS ＝ 60.05 mg of C2H4O2
storage conditions:
  en: Containers—Tight containers.

acetohexamide
type: ChemicalDrugMonograph
pref label:
  en: Acetohexamide
  ja: アセトヘキサミド
monograph id: JP18-acetohexamide
publisher: JP
status: Official
version: 18
molecular formula: C15H20N2O4S
molecular weight: 324.4
definition:
  en: Acetohexamide, when dried, contains not less than 98.
appearance:
  en: Acetohexamide occurs as a white to yellowish white powder. It is freely soluble in N,N-dimethylformamide, sparingly soluble in acetone, slightly soluble in methanol and in ethanol (99.5), and practically insoluble in water. Melting point: about 1859C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.10 g of Acetohexamide in 100 mL of methanol. To 5 mL of the solution add 20 mL of 0.5 mol/L hydrochloric acid TS and 75 mL of methanol, and use the solution as the sample solution (1). Determine the absorption spectrum of the sample solution (1) as directed under Ultraviolet-visible Spectrophotometry <2.24>, using methanol as the blank, and compare the spectrum with the Reference Spectrum 1: both spectra exhibit similar intensities of absorption at the same wavelengths. Separately, to exactly 10 mL of the sample solution (1) add methanol to make ex-actly 50 mL, and use the solution as the sample solution (2). Determine the absorption spectrum of the sample solution (2) as directed under Ultraviolet-visible Spectrophotometry <2.24>, using methanol as the blank, and compare the spec-trum with the Reference Spectrum 2: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Acetohexamide, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 1.5 g of Aceto-hexamide in 40 mL of N,N-dimethylformamide, add 6 mL of dilute nitric acid and N,N-dimethylformamide to make 50 mL. Perform the test using this solution as the test solution. JP XVIII Official Monographs / Acetohexamide 405 Prepare the control solution as follows: to 0.45 mL of 0.01 mol/L hydrochloric acid VS add 6 mL of dilute nitric acid and N,N-dimethylformamide to make 50 mL (not more than 0.011z). Sulfate <1.14>—Dissolve 2.0 g of Acetohexamide in 40 mL of N,N-dimethylformamide, and add 1 mL of dilute hydrochloric acid and N,N-dimethylformamide to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.40 mL of 0.005 mol/L sulfuric acid VS add 1 mL of dilute hydrochloric acid and N,N-dimethylformamide to make 50 mL (not more than 0.010z). Heavy metals <1.07>—Proceed with 1.0 g of Aceto- hexamide according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances (i) Cyclohexylamine—Dissolve exactly 1.0 g of Acetohexamide in exactly 30 mL of 0.5 mol/L sodium hydroxide TS, add exactly 5 mL of hexane, shake vigorously for 60 minutes, allow to stand for 5 minutes, and use the upper layer as the sample solution. Separately, dissolve exactly 50 mg of cyclohexylamine in 0.5 mol/L sodium hydroxide TS to make exactly 50 mL. Pipet 2 mL of this solution, and add 0.5 mol/L sodium hydroxide TS to make exactly 300 mL. Pipet 30 mL of this solution, add exactly 5 mL of hexane, shake vigorously for 60 minutes, allow to stand for 5 minutes, and use the upper layer as the standard solution. Perform the test with exactly 2 mL each of the sample solution and standard solution as directed under Gas Chromatography <2.02> according to the following conditions, and determine the peak area of cyclo-hexylamine by the automatic integration method: the peak area of cyclohexylamine obtained from the sam…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Acetohexamide, previously dried, dissolve in 30 mL of N,N-dimethylfor-mamide, add 10 mL of water, and titrate <2.50> with 0.1 mol/L sodium hydroxide VS (potentiometric titration). Perform a blank determination in the same manner using a solution prepared by adding 19 mL of water to 30 mL of N,N-dimethylformamide, and make any necessary correc- ‌406‌ tion. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 32.44 mg of C15H20N2O4S of the Mass variation test. Foreign insoluble matter <6.06> Perform the test according to Method 2: it meets the requirement.
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

acetylsalicylic-acid
type: ChemicalDrugMonograph
pref label:
  en: Acetylsalicylic Acid
  ja: アスピリン
monograph id: JP18-acetylsalicylic-acid
publisher: JP
status: Official
version: 18
molecular formula: C9H8O4
molecular weight: 180.16
appearance:
  en: Aspirin occurs as white, crystals, granules or powder. It is odorless, and has a slight acid taste. It is freely soluble in ethanol (95) and in acetone, soluble in diethyl ether, and slightly soluble in water. It dissolves in sodium hydroxide TS and in sodium car-bonate TS. In moist air, it gradually hydrolyzes to salicylic acid and acetic acid. Melting point: about 1369C (bath fluid is heated at 1309C previously).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Boil 0.1 g of Aspirin in 5 mL of water for 5 to 6 minutes, cool, and add 1 to 2 drops of iron (III) chloride TS: a red-purple color is produced. Boil 0.5 g of Aspirin in 10 mL of sodium carbonate TS for 5 minutes, and add 10 mL of dilute sulfuric acid: the odor of acetic acid is perceptible, and a white precipitate is produced. Filter the precipitate, add 3 mL of ethanol (95) and 3 mL of sulfuric acid to the filtrate, and heat: the odor of ethyl acetate is perceptible.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity of solution—Dissolve 0.5 g of Aspirin in 10 mL of warm sodium carbonate TS: the solution is clear. Salicylic acid—Dissolve 2.5 g of Aspirin in 25 mL of ethanol (95), and add 1.0 mL of this solution to a solution which is prepared by transferring 1 mL of a freshly prepared dilute ammonium iron (III) sulfate TS to a Nessler tube and diluting with water to 50 mL. Allow to stand for 30 seconds: the solution has no more color than the following control so-lution. Control solution: Dissolve 0.100 g of salicylic acid in water, and add 1 mL of acetic acid (100) and water to make 1000 mL. Add 1.0 mL of this solution to a solution which is prepared by transferring 1 mL of freshly prepared dilute am-monium iron (III) sulfate TS and 1 mL of ethanol (95) to a Nessler tube and diluting with water to 50 mL. Allow to stand for 30 seconds. Chloride <1.03>—Boil 1.8 g of Aspirin in 75 mL of water for 5 minutes, cool, add water to make 75 mL, and filter. To 25 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL, and perform the test using this so-lution as the test solution. Prepare the control solution with 0.25 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.015z). Sulfate <1.14>—To 25 mL of the filtrate obtained in add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solu-tion. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.040z). Heavy metals <1.07>—Dissolve 2.5 g of Aspirin in 30 mL of acetone, add 2 mL of dilute acetic acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution with 2.5 mL of Standard Lead Solution, 30 mL of acetone, 2 mL of dilute acetic acid and water to make 50 mL (not more than 10 ppm). Readily carbonizable substances <1.15>—Weigh 0.5 g of Aspirin, and perform the test. The solution has no more color than Matching Fluid Q. Loss on drying <2.41> Not more than…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 1.5 g of Aspirin, previously dried, add exactly 50 mL of 0.5 mol/L sodium hydroxide VS, and boil gently for 10 minutes under a reflux condenser with a carbon dioxide-absorbing tube (soda lime). Cool, and titrate <2.50> immediately the excess sodium hydroxide with 0.25 mol/L sulfuric acid VS (indicator: 3 drops of phenol-phthalein TS). Perform a blank determination in the same manner. Each mL of 0.5 mol/L sodium hydroxide VS ＝ 45.04 mg of C9H8O4
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

aciclovir
type: ChemicalDrugMonograph
pref label:
  en: Aciclovir
  ja: アシクロビル
monograph id: JP18-aciclovir
publisher: JP
status: Official
version: 18
molecular formula: C8H11N5O3
molecular weight: 225.2
cas number: 59277-89-3
definition:
  en: Aciclovir contains not less than 98.
appearance:
  en: Aciclovir occurs as a white to pale yellow-white crystalline powder. It is slightly soluble in water and very slightly soluble in ethanol (99.5). It dissolves in 0.1 mol/L hydrochloric acid TS and in dilute sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Aciclovir in 0.1 mol/L hydrochloric acid TS (1 in 100,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of a solution of Aciclovir RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Aciclovir as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Aciclovir RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Aciclovir in 20 mL of dilute sodium hydroxide TS: the so-lution is clear and is not more colored than the following control solution. Control solution: To 2.5 mL of Matching Fluid F add diluted dilute hydrochloric acid (1 in 10) to make 100 mL. ‌Heavy metals <1.07>—Proceed with 1.0 g of Aciclovir according to Method 2, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Use the sample solution ob-tained in the Assay as the sample solution. Separately, weigh accurately about 25 mg of guanine, dissolve in 50 mL of dilute sodium hydroxide TS, and add the mobile phase to make exactly 100 mL. Pipet 2 mL of this solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine the peak areas of guanine, AT and AS, and calculate the amount of guanine by the follow-ing equation: it is not more than 0.7z. Determine each peak area from the sample solution by the automatic integration method, and calculate the amount of each related substance other than aciclovir and guanine by the area percentage method: it is not more than 0.2z. Furthermore, the sum of the amount of guanine calculated above and the amounts of related substances determined by the area percentage method is not more than 1.5z. Amount (mg) of aciclovir (C8H11N5O3) ＝ MS × AT/AS MS: Amount (mg) of Aciclovir RS taken, calculated on the anhydrous basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 10 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 mm in particle diameter). Column temperature: A constant temperature of about 20…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 20 mg each of Aciclovir and Aciclovir RS (separately determine the water <2.48> in the same manner as Aciclovir), dissolve each in 1 mL of dilute sodium hydroxide TS, add the mobile phase to make exactly 20 mL each, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of aciclovir in each solution. ing conditions, the relative standard deviation of the peak area of aciclovir is not more than 1.0z.
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

aclarubicin-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Aclarubicin Hydrochloride
  ja: アクラルビシン塩酸塩
monograph id: JP18-aclarubicin-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C42H53NO15.HCl
molecular weight: 848.33
definition:
  en: Aclarubicin Hydrochloride is the hydrochloride of an anthracycline substance having antitumor activity produced by the growth of Streptomyces galilaeus. It contains not less than 920 mg (potency) and not more than 975 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Aclarubicin Hydrochloride occurs as a yellow to pale orange-yellow powder. It is very soluble in chloroform and in methanol, freely soluble in water, and slightly soluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Aclarubicin Hydrochloride in diluted methanol (4 in 5) (3 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi- ties of absorption at the same wavelengths. ‌Determine the infrared absorption spectrum of Aclarubicin Hydrochloride as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Aclarubicin Hydrochloride in methanol (1 in 200) responds to Qualitative Tests <1.09> (2) for chlo-ride. D Optical rotation <2.49> [a]20: －146 – －1629(50 mg calcu-lated on the anhydrous basis, water, 10 mL, 100 mm). pH <2.54> The pH of a solution obtained by dissolving 0.05 g of Aclarubicin Hydrochloride in 10 mL of water is between 5.5 and 6.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.10 g of Aclarubicin Hydrochloride in 10 mL of water: the solu-tion is clear and yellow to pale orange-yellow. Heavy metals <1.07>—Proceed with 1.0 g of Aclaru- bicin Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Related substances—Dissolve 10 mg of Aclarubicin Hydrochloride in 10 mL of the mobile phase, and use this solution as the sample solution. Perform the test with 20 mL of the sample solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and de-termine each peak area by the automatic integration method. Calculate the amount of the related substances by the area and allow to stand for 60 minutes. To 1.0 mL of this solu-tion add 1.0 mL of 0.2 mol/L sodium hydroxide TS, 1.0 mL of phosphate buffer solution (pH 8.0) and 1.0 mL of chlo-roform, shake vigorously, and take the chloroform layer. When the procedure is run with 20 mL of the chloroform under the above operating conditions, aclarubicin and 1-deoxypyrromycin are eluted in this order with the resolution between these peaks being not less than 3.0. System repeatability: When the test is repeated 5 times with 20 mL of the sample solution under the above operating conditions, the relative standard deviation of the peak area of aclarubicin is not more than 2.0z. Water <2.48> Not more than 3.5z (0.1 g, volumetric titra-tion, direct titration). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Aclarubicin Hydro-chloride, equivalent to about 20 mg (potency), and dissolve in diluted methanol (4 in 5) to make exactly 100 mL. Pipet 15 mL of this solution, add diluted methanol (4 in 5) to make exactly 100 mL, and use this solution as the sample solution. Separately, weigh accurately an amount of Aclarubicin RS, equivalent to about 20 mg (potency), add 0.6 mL of diluted hydrochloric acid (1 in 250) and diluted methanol (4 in 5) to make exactly 100 mL. Pipet 15 mL of this solution, add diluted methanol (4 in 5) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with the sample solution and standard solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and determine the absorbances, AT and AS, at 433 nm. percentage method: the amount of aklavinone having the relative retention time of about 0.6 to aclarubicin is not more than 0.2z, aclacinomycin L1 having the relative retention Amount [ mg (potency)] of aclarubicin (C ＝ MS × AT/AS × 1000 42H53NO15) time of about 0.75 is not more than 0.5z, 1-deoxypyrromy-cin having the relative retention time of about 1.7 is not more than 1.5z and aclacinomycin S1 having the relative retention time of about 2.3 is not more than 0.5z, and the total amount of the peaks other than aclarubicin and the peaks mentioned above is not more than 1.0z of the peak area of aclarubicin. Operating conditions— Detector: A visible absorption photometer (wavelength: 436 nm). Column: A stainless steel column 3.9 mm in inside diame-ter and 30 cm in length, packed with silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of chloroform, methanol, acetic acid (100), water and triethylamine (6800:2000:1000:200:1). Flow rate: Adjust so that the retention time of aclarubicin is about 5 minutes. Time span of measurement: As long as about 4 times of the retention time of aclaru…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant and at 59C or below.
type: PharmacopoeiaMonograph

adeps-lanae-purificatus
type: ChemicalDrugMonograph
pref label:
  en: Adeps Lanae Purificatus
  ja: 精製ラノリン
monograph id: JP18-adeps-lanae-purificatus
publisher: JP
status: Official
version: 18
appearance:
  en: Purified Lanolin is a light yellow to yellowish brown, viscous, ointment-like substance, and has a faint, ‌2062 Lard / Crude Drugs and Related Drugs characteristic but not rancid odor. It is very soluble in diethyl ether and in cyclohexane, freely soluble in tetrahydrofuran and in toluene, and very slightly soluble in ethanol (95). It is practically insoluble in water, but miscible without separation with about twice its mass of water, retaining ointment-like viscosity. Melting point: 37 – 439C
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Superimpose carefully 1 mL of a solution of Purified Lanolin in cyclohexane (1 in 50) on 2 mL of sulfuric acid: a red-brown color develops at the zone of contact, and the sulfuric acid layer shows a green fluorescence. Acid value <1.13> Not more than 1.0. Iodine value 18 – 36 Weigh accurately about 0.8 g of Purified Lanolin in a glass-stoppered 500-mL flask, add 20 mL of cyclohexane to dissolve, and add exactly 25 mL of Hanus' TS, and mix well. If a clear solution is not obtained, add more cyclohexane to make clear, and allow the mixture to stand for 1 hour between 209C and 309C in light-resistant, well-closed containers, with occasional shaking. Add 20 mL of a solution of potassium iodide (1 in 10) and 100 mL of water, shake, and titrate the liberated iodine with 0.1 mol/L sodium thiosulfate VS (indicator: 1 mL of starch TS). Per-form a blank determination in the same manner. Iodine value ＝ (a － b) × 1.269/M M: amount (g) of Purified Lanolin taken a: Volume (mL) of 0.1 mol/L sodium thiosulfate VS used in the blank determination b: Volume (mL) of 0.1 mol/L sodium thiosulfate VS used in the titration of the sample
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acid or alkali—To 5 g of Purified Lanolin add 25 mL of water, boil for 10 minutes, and cool. Add water to restore the previous mass, and separate the aqueous layer: the aqueous layer is neutral. Chloride <1.03>—To 2.0 g of Purified Lanolin add 40 mL of water, boil for 10 minutes, and cool. Add water to re-store the previous mass, and filter. To 20 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL. Use this solution as the test solution, and perform the test. Pre-pare the control solution with 1.0 mL of 0.01 mol/L hydro-chloric acid VS (not more than 0.036z). Ammonia—To 10 mL of the aqueous layer obtained in (1) add 1 mL of sodium hydroxide TS, and boil: the gas evolved does not turn moistened red litmus paper to blue. Water-soluble organic substances—To 5 mL of the aqueous layer obtained in (1) add 0.25 mL of 0.002 mol/L potassium permanganate VS, and allow to stand for 5 minutes: the red color of the solution does not disappear. Petrolatum—Dissolve 1.0 g of Purified Lanolin in 10 mL of a mixture of tetrahydrofuran and isooctane (1:1), and use this solution as the sample solution. And dissolve 20 mg of vaseline in 10 mL of a mixture of tetrahydrofuran and isooctane (1:1), and use this solution as the standard solu-tion. Perform the test with the sample solution as directed under Thin-layer Chromatography <2.03>. Spot 25 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with isooctane to a distance of about 10 cm, and air-dry the plate. Spray evenly diluted sulfuric acid (1 in 2) on the plate, heat the plate at 809C for 5 minutes, cool, and examine under ultraviolet light (main wavelength: 365 nm): no fluo-rescent spot is observable same level of the spot of standard solution. Use a thin-layer plate previously developed with isooctane to the upper end, dried in air, and heated at 1109C for 60 minutes. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours).…
storage conditions:
  en: Containers—Well-closed contain-ers.

adeps-suillus
type: ChemicalDrugMonograph
pref label:
  en: Adeps Suillus
  ja: 豚脂
monograph id: JP18-adeps-suillus
publisher: JP
status: Official
version: 18
appearance:
  en: Lard occurs as a white, soft, unctuous mass, and has a faint, characteristic odor and a bland taste. It is freely soluble in diethyl ether and in petroleum ether, very slightly soluble in ethanol (95), and practically insoluble in water. Melting point: 36 – 429C Congealing point of the fatty acids: 36 – 429C Acid value <1.13> Not more than 2.0. Saponification value <1.13> 195 – 203 Iodine value <1.13> 46 – 70
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Moisture and coloration—Melt 5 g of Lard by heating on a water bath: it forms a clear liquid, from which no water separates. Observe the liquid in a layer 10 mm thick: the liquid is colorless to slightly yellow. Alkalinity—To 2.0 g of Lard add 10 mL of water, melt by warming on a water bath, and shake vigorously. After cooling, add 1 drop of phenolphthalein TS to the sepa-rated aqueous layer: the layer is colorless. Chloride <1.03>—To 1.5 g of Lard add 30 mL of ethanol (95), heat under a reflux condenser for 10 minutes, and filter after cooling. To 20 mL of the filtrate add 5 drops of a solution of silver nitrate in ethanol (95) (1 in 50): the opalescence of the mixture does not exceed that of the fol-lowing control solution. Control solution: To 1.0 mL of 0.01 mol/L hydrochloric acid VS add ethanol (95) to make 20 mL, and add 5 drops of a solution of silver nitrate in ethanol (95) (1 in 50). Beef tallow—Dissolve 5 g of Lard in 20 mL of diethyl ether, stopper lightly with absorbent cotton, and allow to stand at 209C for 18 hours. Collect the separated crystals, moisten them with ethanol (95), and examine under a micro-scope of 200 magnifications: the crystals are in the form of rhomboidal plates grouped irregularly, and do not contain prisms or needles grouped in fan-shaped clusters.
storage conditions:
  en: Containers—Well-closed contain-ers.

adsorbed-diphtheria-tetanus-combined-toxoid
type: ChemicalDrugMonograph
pref label:
  en: Adsorbed Diphtheria-Tetanus Combined Toxoid
  ja: 沈降ジフテリア破傷風混合トキソイド
monograph id: JP18-adsorbed-diphtheria-tetanus-combined-toxoid
publisher: JP
status: Official
version: 18
appearance:
  en: Adsorbed Diphtheria-Tetanus Combined Tox-oid becomes a homogeneous, whitish turbid liquid on shak-ing. ‌874 Dipyridamole

adsorbed-diphtheria-toxoid-for-adult-use
type: ChemicalDrugMonograph
pref label:
  en: Adsorbed Diphtheria Toxoid for Adult Use
  ja: 成人用沈降ジフテリアトキソイド
monograph id: JP18-adsorbed-diphtheria-toxoid-for-adult-use
publisher: JP
status: Official
version: 18
appearance:
  en: Adsorbed Diphtheria Toxoid for Adult Use becomes a homogeneous, whitish turbid liquid on shaking. Adsorbed Diphtheria-Purified Pertussis-Tetanus Combined Vaccine

adsorbed-tetanus-toxoid
type: ChemicalDrugMonograph
pref label:
  en: ‌Adsorbed Tetanus Toxoid‌‌
  ja: 沈降破傷風トキソイド
monograph id: JP18-adsorbed-tetanus-toxoid
publisher: JP
status: Official
version: 18
appearance:
  en: Adsorbed Tetanus Toxoid becomes a uniform white-turbid liquid on shaking. Tetracaine Hydrochloride

afloqualone
type: ChemicalDrugMonograph
pref label:
  en: Afloqualone
  ja: アフロクアロン
monograph id: JP18-afloqualone
publisher: JP
status: Official
version: 18
molecular formula: C16H14FN3O
molecular weight: 283.3
definition:
  en: Afloqualone, when dried, contains not less than 98.
appearance:
  en: Afloqualone occurs as white to light yellow, crystals or crystalline powder. It is soluble in acetonitrile, sparingly soluble in ethanol (99.5), and practically insoluble in water. It is gradually colored by light. Melting point: about 1979C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Conduct this procedure without ex-posure to light, using light-resistant containers. Determine the absorption spectrum of a solution of Afloqualone in ethanol (99.5) (1 in 150,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Afloqualone, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity or alkalinity—Take 1.0 g of Afloqua-lone in a light-resistant vessel, add 20 mL of freshly boiled and cooled water, shake well, and filter. To 10 mL of the fil-trate add 2 drops of bromothymol blue TS: a yellow color develops. The color changes to blue by adding 0.20 mL of 0.01 mol/L sodium hydroxide TS. Heavy metals <1.07>—Proceed with 2.0 g of Afloqua-lone in a platinum crucible according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 10 mg of Afloqualone in 25 mL of the mobile phase, and use this solution as the sample solution. Pipet 3 mL of the sam-ple solution, add the mobile phase to make exactly 100 mL. Pipet 2 mL of this solution, add the mobile phase to make exactly 20 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solu-tion and standard solution as directed under Liquid Chroma-tography <2.01> according to the following conditions. De-termine each peak area by the automatic integration method: the total area of the peaks other than afloqualone from the sample solution is not larger than the peak area of afloqua-lone from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 7.2 g of disodium hydrogen phosphate dodecahydrate in 1000 mL of water, adjust to pH 5.5 with diluted phosphoric acid (1 in 10). To 600 mL of this solution add 400 mL of acetonitrile. Flow rate: Adjust so that the retention time of afloqua-lone is about 5.5 minutes. Time span of measurement: About 4 times as long as the …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Afloqualone, previ-ously dried, dissolve in 10 mL of hydrochloric acid and 40 mL of water, and add 10 mL of a solution of potassium bro-mide (3 in 10). After cooling at 159C or below, titrate <2.50> with 0.1 mol/L sodium nitrite VS according to the potentio-metric titration or amperometric titration under the Electro-metric Titration method. Each mL of 0.1 mol/L sodium nitrite ＝ 28.33 mg of C16H14FN3O
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

agar-pulveratum
type: ChemicalDrugMonograph
pref label:
  en: Agar Pulveratum
  ja: カンテン末
monograph id: JP18-agar-pulveratum
publisher: JP
status: Official
version: 18
appearance:
  en: Powdered Agar appears as a white powder, is odorless, and is tasteless and mucilaginous. Under a microscope <5.01>, Powdered Agar, immersed in olive oil or liquid paraffin, reveals angular granules with stri-ations or nearly spheroidal granules 5 to 60 mm in diameter. It becomes transparent in chloral hydrate TS. It is practically insoluble in organic solvents. A boiling solution of Powdered Agar (1 in 100) is neutral.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To a part of Powdered Agar add drop-wise iodine TS: a dark blue to reddish purple color develops. (2) Dissolve 1 g of Powdered Agar in 65 mL of water by boiling for 10 minutes with constant stirring, and add a sufficient amount of hot water to maintain the original volume lost by evaporation: the solution is clear. Cool the solution between 309C and 399C: the solution forms a firm, resilient gel, which does not melt below 859C.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfuric acid—Dissolve 1.0 g of Powdered Agar in 100 mL of water by boiling: the solution is not acid. Sulfurous acid and starch—To 5 mL of the solution obtained in (1) add 2 drops of iodine TS: the solution is not decolorized immediately, and does not show a blue color. Insoluble matter—To 7.5 g of Powdered Agar add 500 mL of water, boil for 15 minutes, and add water to make exactly 500 mL. Take exactly 100 mL of the solution, add 100 mL of hot water, heat to boiling, filter while hot through a tared glass filter (G3), wash the residue with a small amount of hot water, and dry the residue at 1059C for 3 hours: the mass of the residue is not more than 15.0 mg. Water absorption—To 5.0 g of Powdered Agar add water to make 100 mL, shake well, allow to stand at 259C for 24 hours, and filter through moistened glass wool in a 100-mL graduated cylinder: the volume of the filtrate is not more than 75 mL. Loss on drying <5.01> Not more than 22.0z (6 hours). Total ash <5.01> Not more than 4.5z. Acid-insoluble ash <5.01> Not more than 0.5z.
storage conditions:
  en: Containers—Tight containers.

agar
type: ChemicalDrugMonograph
pref label:
  en: Agar
  ja: カンテン
monograph id: JP18-agar
publisher: JP
status: Official
version: 18
appearance:
  en: White, translucent rectangular column, string or flakes. Rectangular column about 26 cm in length, 4 cm square in cross section; a string of about 35 cm in length and about 3 mm in width; flakes about 3 mm in length; externally, with wrinkles and somewhat lustrous, light and pliable. Odorless; tasteless and mucilaginous. It is practically insoluble in organic solvents. A boiling solution of Agar (1 in 100) is neutral.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To a fragment of Agar add dropwise iodine TS: a dark blue to reddish purple color develops. (2) Dissolve 1 g of Agar in 65 mL of water by boiling for 10 minutes with constant stirring, and add a sufficient amount of hot water to make up the water lost by evapora-tion: the solution is clear. Cool the solution between 309C and 399C: the solution forms a firm, resilient gel, which does not melt below 859C.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfuric acid—Dissolve 1.0 g of Agar in 100 mL of water by boiling: the solution is not acidic. Sulfurous acid and starch—To 5 mL of the solution obtained in (1) add 2 drops of iodine TS: the solution is not decolorized immediately, and does not show a blue color. Insoluble matter—To 7.5 g of Agar add 500 mL of water, boil for 15 minutes, and add water to make exactly 500 mL. Measure exactly 100 mL of the solution, add 100 mL of hot water, heat to boiling, filter while hot through a tared glass filter (G3), wash the residue with a small amount of hot water, and dry the residue at 1059C for 3 hours: the mass of the residue is not more than 15.0 mg. Water absorption—To 5.0 g of Agar add water to make 100 mL, shake well, allow to stand at 259C for 24 hours, and filter through moistened glass wool in a 100-mL graduated cylinder: the volume of the filtrate is not more than 75 mL. Loss on drying <5.01> Not more than 22.0z (6 hours). Total ash <5.01> Not more than 4.5z. Acid-insoluble ash <5.01> Not more than 0.5z.
storage conditions:
  en: Containers—Well-closed contain-ers.

ajmaline
type: ChemicalDrugMonograph
pref label:
  en: Ajmaline
  ja: アジマリン
monograph id: JP18-ajmaline
publisher: JP
status: Official
version: 18
molecular formula: C20H26N2O2
molecular weight: 326.43
definition:
  en: Ajmaline, when dried, contains not less than 96.
appearance:
  en: Ajmaline occurs as a white to pale yellow crystalline powder. It is odorless, and has a bitter taste. It is freely soluble in acetic anhydride and in chloroform, sparingly soluble in methanol, in ethanol (95), in acetone and in diethyl ether, and very slightly soluble in water. It dissolves in dilute hydrochloric acid. Melting point: about 1959C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.05 g of Ajmaline in 5 mL of methanol, and use this solution as the sample solution. Add 3 mL of nitric acid to 1 mL of the sample solution: a deep red color develops. (2) Spot the sample solution of (1) on filter paper, and spray Dragendorff's TS: an orange color develops.
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

alacepril
type: ChemicalDrugMonograph
pref label:
  en: Alacepril
  ja: アラセプリル
monograph id: JP18-alacepril
publisher: JP
status: Official
version: 18
molecular formula: C20H26N2O5S
molecular weight: 406.5
cas number: 74258-86-9
definition:
  en: Alacepril, when dried, contains not less than 98.
appearance:
  en: Alacepril occurs as white, crystals or crystal-line powder. It is freely soluble in methanol, soluble in ethanol (95), and slightly soluble in water. It dissolves in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 20 mg of Alacepril add 0.1 g of so-dium hydroxide, and heat gradually to melt: the gas evolved changes the color of a moisten red litmus paper to blue. After cooling, to the melted substance add 2 mL of water, shake, and add 1 mL of lead (II) acetate TS: a brown to black precipitate is formed. (2) Determine the infrared absorption spectrum of Alacepril, previously dried, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －81 – －859(after drying, 0.25 g, ethanol (95), 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 0.5 g of Alacepril in 30 mL of methanol, add 6 mL of dilute nitric acid and water to make 50 mL, and perform the test with this solution as the test solution. Prepare the control solution as follows: to 0.30 mL of 0.01 mol/L hydrochloric acid VS add 30 mL of meth-anol, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.021z). Sulfate <1.14>—Dissolve 0.5 g of Alacepril in 30 mL of methanol, add 1 mL of dilute hydrochloric acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.50 mL of 0.005 mol/L sulfuric acid VS add 30 mL of methanol, 1 mL of dilute hydrochloric acid and water to make 50 mL (not more than 0.048z). Heavy metals <1.07>—Proceed with 1.0 g of Alacepril according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 50 mg of Alacepril in 5 mL of ethanol (95), and use this solution as the sample solu-tion. Pipet 1 mL of the sample solution, add ethanol (95) to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the area of the peak other than alacepril from the sample solution is not larger than 2/5 times the peak area of alacepril from the standard solution, and the total area of the peaks other than alacepril from the sample solution is not larger than the peak area of alacepril from the standard solution. For the areas of the peaks, having the relative retention times of about 2.3 and about 2.6 to alacepril, multiply their correction factors, 1.5 and 1.9, respectively. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stai…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Alacepril, previ-ously dried, dissolve in 75 mL of a mixture of methanol and water (2:1), and titrate <2.50> with 0.1 mol/L sodium hy-droxide VS (potentiometric titration). Perform a blank de-termination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 40.65 mg of C20H26N2O5S
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

alcohol-for-disinfection
type: ChemicalDrugMonograph
pref label:
  en: Alcohol for Disinfection
  ja: 消毒用エタノール
monograph id: JP18-alcohol-for-disinfection
publisher: JP
status: Official
version: 18
appearance:
  en: Ethanol for Disinfection is a colorless, clear liquid. It is miscible with water. It burns with a light blue flame on ignition. It is volatile.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of Ethanol for Disinfection add 2 mL of iodine TS and 1 mL of sodium hydroxide TS, and mix: light yellow precipitates appear. (2) To 1 mL of Ethanol for Disinfection add 1 mL of acetic acid (100) and 3 drops of sulfuric acid, and heat: the odor of ethyl acetate is produced. Specific gravity <2.56> d 15: 0.86027 – 0.87264
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Proceed as directed in the Purity under Ethanol, with the exeption of (4), which is changed as follows. (4) Other impurities (absorbance)—Perform the test with Ethanol for Disinfection as directed under Ultraviolet-visible Spectorophotometry <2.24>: the absorbances at 240 nm, be-tween 250 nm and 260 nm and between 270 nm and 340 nm are not more than 0.40, 0.30, and 0.10, respectively. The ab-sorption spectrum determined in a 5-cm cell using water as a ‌JP XVIII Official Monographs / Ether 967‌ blank shows a smooth absorption curve between 235 nm and 340 nm.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

alcohol
type: ChemicalDrugMonograph
pref label:
  en: Alcohol
  ja: エタノール
monograph id: JP18-alcohol
publisher: JP
status: Official
version: 18
cas number: 64-17-5
appearance:
  en: Ethanol is a clear, colorless liquid. It is miscible with water. It is flammable and burns with a light blue flame on igni-tion. It is volatile.◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Ethanol as directed in the liquid film method under In-frared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wave numbers. Specific gravity <2.56> d 15: 0.80872 – 0.81601
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Ethambutol Hydrochloride in 10 mL of water: the solu-tion is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g Etham- butol Hydrochloride according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Stand- Ethanol [64-17-5] This monograph is harmonized with the European Phar-macopoeia and the U.S. Pharmacopeia. The parts of the text that are not harmonized are marked with symbols (◆ ◆). Information on the harmonization with the European Pharmacopoeia and the U.S. Pharmacopeia is available on the website of the Pharmaceuticals and Medical Devices Agency. Ethanol contains not less than 95.1 volz and not more than 96.9 volz (by specific gravity) of ethanol (C H O) at 159C. ard Lead Solution (not more than 10 ppm). 2 6 Arsenic <1.11>—Prepare the test solution with 1.0 g of Ethambutol Hydrochloride according to Method 1, and perform the test (not more than 2 ppm). 2-Aminobutanol—Dissolve 5.0 g of Ethambutol Hy-drochloride in methanol to make exactly 100 mL, and use this solution as the sample solution. Separately, dissolve 0.05 g of 2-amino-1-butanol in methanol to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 2 mL each of the sample solu-tion and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, acetic acid (100), hydrochloric acid and water (11:7:1:1) to a distance of about 10 cm, air-dry the plate, and heat at 1059C for 5 minutes. Cool, spray evenly ninhydrin-L-ascorbic acid TS upon the plate, air-dry the plate, and heat at 1059C for 5 minutes: the spot obtained from the sample Description Ethanol is a clear, colorless liquid. It is miscible with water. It is flammable and burns with a light blue flame on igni-tion. It is volatile.◆ Identification Determine the infrared absorption spectrum …
storage conditions:
  en: ◆Containers—Tight containers.◆ Storage—Without exposure to light.
type: PharmacopoeiaMonograph

aldioxa
type: ChemicalDrugMonograph
pref label:
  en: Aldioxa
  ja: アルジオキサ
monograph id: JP18-aldioxa
publisher: JP
status: Official
version: 18
molecular formula: C4H7AlN4O5
molecular weight: 218.1
cas number: 5579-81-7
definition:
  en: Aldioxa is a condensation product of allantoin and aluminum hydroxide. When dried, it contains not less than 65.
appearance:
  en: Aldioxa occurs as a white powder. It is practically insoluble in water and in ethanol (99.5). It dissolves in dilute hydrochloric acid. A solution of Aldioxa in sodium fluoride-hydrochloric acid TS (1 in 100) shows no optical rotation. Melting point: about 2309C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of Aldioxa, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. (2) To 0.2 g of Aldioxa add 10 mL of dilute hydrochloric acid, dissolve by warming, and cool: the solution responds to Qualitative Tests <1.09> for aluminum salt.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—To 0.10 g of Aldioxa add 6 mL of dilute nitric acid, boil to dissolve with shaking for 5 minutes, cool, and add water to make 50 mL. Perform the test using this solution as the test solution. Prepare the con-trol solution with 0.40 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.142z). (2) Heavy metals <1.07>—To 1.0 g of Aldioxa add 3 mL of hydrochloric acid and 3 mL of water, heat gently to boil with shaking, and evaporate on a water bath to dryness. To the residue add 30 mL of water, shake under warming, cool, filter, and to the filtrate add 2 mL of dilute acetic acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: evaporate 3 mL of hydrochloric acid on a water bath to dry-ness, and add 2.0 mL of Standard Lead Solution, 2 mL of dilute acetic acid and water to make 50 mL (not more than 20 ppm). Loss on drying <2.41> Not more than 4.0z (1 g, 1059C, 2 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Allantoin—Weigh accurately about 0.1 g of Aldioxa, previously dried, dissolve in 50 mL of dilute sulfu-ric acid by heating, cool, and add water to make exactly 100 mL. Pipet 10 mL of this solution, and perform the test as directed under Nitrogen Determination <1.08>. Each mL of 0.005 mol/L sulfuric acid VS ＝ 0.3953 mg of C4H6N4O3 (2) Aluminum—Weigh accurately about 0.2 g of Aldioxa, previously dried, dissolve carefully in 50 mL of dilute hydrochloric acid by heating, cool, and add dilute hydrochloric acid to make exactly 100 mL. Pipet 4 mL of this solution, add water to make exactly 25 mL, and use this solution as the sample solution. Separately, pipet a suitable quantity of Standard Aluminum Stock Solution, dilute with water so that each mL of the solution contains not less than 16.0 mg and not more than 64.0 mg of aluminum (Al: 26.98), and use this solution as the standard solution. Perform the test with the sample solution and standard solution as di-rected under Atomic Absorption Spectrophotometry <2.23> according to the following conditions, and calculate the alu-minum content of the sample solution from the calibration curve obtained from the absorbance of the standard solu-tion. Gas: Combustible gas—Acetylene. Supporting gas—Nitrous oxide. Lamp: An aluminum hollow cathode lamp. Wavelength: 309.2 nm.
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

alimemazine-tartrate
type: ChemicalDrugMonograph
pref label:
  en: Alimemazine Tartrate
  ja: アリメマジン酒石酸塩
monograph id: JP18-alimemazine-tartrate
publisher: JP
status: Official
version: 18
cas number: 41375-66-0
definition:
  en: Alimemazine Tartrate, when dried, contains not less than 98.
appearance:
  en: Alimemazine Tartrate occurs as a white pow-der. It is odorless, and has a bitter taste. It is freely soluble in water and in acetic acid (100), spar-ingly soluble in ethanol (95), and practically insoluble in diethyl ether. The pH of a solution of 1.0 g of Alimemazine Tartrate in 50 mL of water is between 5.0 and 6.5. It is gradually colored by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2 mL of a solution of Alimemazine Tartrate (1 in 100) add 1 drop of iron (III) chloride TS: a red-brown color is produced, and immediately a yellow pre-cipitate is formed. Dissolve 1 g of Alimemazine Tartrate in 5 mL of water, add 3 mL of sodium hydroxide TS, extract with two 10-mL portions of diethyl ether [use the aqueous layer ob-tained in the Identification (4)]. Shake the combined diethyl ether extracts with 3 g of anhydrous sodium sulfate, filter, and evaporate the diethyl ether with the aid of a current of air. Dry the residue in a desiccator (in vacuum, phosphorus (V) oxide) for 16 hours: it melts <2.60> between 669C and 709C. Determine the absorption spectrum of a solution of Alimemazine Tartrate (1 in 100,000) as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. The aqueous layer, obtained in the identification (2), when neutralized with dilute acetic acid, responds to Qualita-tive Tests <1.09> (1) and (2) for tartrate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Alimemazine Tartrate in 20 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Alimemazine Tartrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Alimemazine Tartrate according to Method 3, and per-form the test. Use a solution of magnesium nitrate hexahy-drate in ethanol (95) (1 in 5) (not more than 2 ppm). Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.8 g of Alimemazine Tar-trate, previously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from red through brown to green-brown (indicator: 2 mL of p-naphtholbenzein TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 37.35 mg of (C18H22N2S)2.C4H6O6
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

allopurinol
type: ChemicalDrugMonograph
pref label:
  en: Allopurinol
  ja: アロプリノール
monograph id: JP18-allopurinol
publisher: JP
status: Official
version: 18
molecular formula: C5H4N4O
molecular weight: 136.11
definition:
  en: Allopurinol, when dried, contains not less than 98.
appearance:
  en: Allopurinol occurs as white to pale yellow-white, crystals or crystalline powder. It is slightly soluble in N,N-dimethylformamide, and very slightly soluble in water and in ethanol (99.5). It dissolves in ammonia TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a JP XVIII Official Monographs / Allopurinol Tablets 431 ‌solution of Allopurinol (1 in 200,000) as directed under Ul-traviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Allopurinol, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Allopurinol according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Allopurinol according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 50 mg of Allopurinol in 10 mL of ammonia TS, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add ammonia TS to make exactly 500 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of cellulose with fluorescent indicator for thin-layer chromatography. Develop the plate with ammonia TS-satu-rated 1-butanol to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.16 g of Allopurinol, previ-ously dried, dissolve in 70 mL of N,N-dimethylformamide by warming. Cool, and titrate <2.50> with 0.1 mol/L tetra-methylammonium hydroxide VS (potentiometric titration). To 70 mL of N,N-dimethylformamide add 12 mL of water, perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L tetramethylammonium hydroxide VS ＝ 13.61 mg of C5H4N4O
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

alminoprofen
type: ChemicalDrugMonograph
pref label:
  en: Alminoprofen
  ja: アルミノプロフェン
monograph id: JP18-alminoprofen
publisher: JP
status: Official
version: 18
molecular formula: C13H17NO2
molecular weight: 219.28
definition:
  en: Alminoprofen, when dried, contains not less than 99.
appearance:
  en: Alminoprofen occurs as white to pale yellow, crystals or crystalline powder. It is freely soluble in ethanol (99.5) and in acetic acid (100), and very slightly soluble in water. It gradually turns brown on exposure to light. A solution of Alminoprofen in ethanol (99.5) (1 in 10) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Alminoprofen in ethanol (99.5) (3 in 500,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Alminoprofen as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Alminoprofen, previously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 21.93 mg of C13H17NO2 ‌JP XVIII Official Monographs / Alminoprofen Tablets 433
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

alprazolam
type: ChemicalDrugMonograph
pref label:
  en: ‌Alprazolam
  ja: アルプラゾラム
monograph id: JP18-alprazolam
publisher: JP
status: Official
version: 18
molecular formula: C17H13ClN4
molecular weight: 308.76
appearance:
  en: Alprazolam occurs as white, crystals or crys-talline powder. It is freely soluble in chloroform, soluble in methanol and in ethanol (95), sparingly soluble in acetic anhydride, and practically insoluble in water. It dissolves in dilute nitric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Alprazolam in ethanol (95) (1 in 200,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Dissolve 0.05 g of Alprazolam in 0.7 mL of deu-terochloroform for nuclear magnetic resonance spectros-copy, and determine the spectrum of this solution using of about 10 cm, and air-dry the plate. Examine under ultra-violet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, reduced pressure not exceeding 0.67 kPa, 609C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of Alprazolam, previously dried, dissolve in 100 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (poten-tiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 15.44 mg of C17H13ClN4
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

alprenolol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Alprenolol Hydrochloride
  ja: アルプレノロール塩酸塩
monograph id: JP18-alprenolol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C15H23NO2.HCl
molecular weight: 285.81
definition:
  en: Alprenolol Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Alprenolol Hydrochloride occurs as white, crystals or crystalline powder. It is freely soluble in water, in ethanol (95) and in acetic acid (100), slightly soluble in acetic anhydride, and practi-cally insoluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2 mL of a solution of Alprenolol Hydrochloride (1 in 100) add 0.05 mL of copper (II) sulfate TS and 2 mL of sodium hydroxide TS: a blue-purple color develops. To this solution add 1 mL of diethyl ether, shake well, and allow to stand: a red-purple color develops in the diethyl ether layer. Dissolve 0.05 g of Alprenolol Hydrochloride in 5 mL of water, add 1 to 2 drops of bromine TS, and shake: the color of the test solution disappears. Determine the absorption spectrum of a solution of Alprenolol Hydrochloride in ethanol (95) (1 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Alprenolol Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Alprenolol Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> for chloride. JP XVIII Official Monographs / Alprostadil 435 pH <2.54> Dissolve 1.0 g of Alprenolol Hydrochloride in 10 mL of water: the pH of this solution is between 4.5 and 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 0.5 g of Alprazolam in 10 mL of dilute nitric acid, and add water to make 50 mL. Perform the test using this solution as the test solution. Pre-pare the control solution with 0.20 mL of 0.01 mol/L hydro-chloric acid VS (not more than 0.014z). Heavy metals <1.07>—Proceed with 2.0 g of Alprazolam according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 50 mg of Alprazolam in 10 mL of methanol, and use this solution as the sample so-lution. Pipet 1 mL of the sample solution, add methanol to make exactly 100 mL, then pipet 1 mL of this solution, add methanol to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 20 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop with a mixture of acetone, hexane, ethyl acetate and ethanol (95) (4:2:2:1) to a distance Description Alprenolol Hydrochloride occurs as white, crystals or crystalline powder. It is freely soluble in water, in ethanol (95) and in acetic acid (100), slightly soluble in acetic anhydride, and practi-cally insoluble in diethyl ether. Identification (1) To 2 mL of a solution of Alprenolol Hydrochloride (1 in 100) add 0.05 mL of copper (II) sulfate TS and 2 mL of sodium hydroxide TS: a blue-purple color develops. To this solution add 1 mL of diethyl ether, shake well, and allow to stand: a red-purple color develops in the diethyl ether layer. Dissolve 0.05 g of Alprenolol Hydrochloride in 5 mL of water, add 1 to 2 drops of bromine TS, and shake: the color of the test solution disappears. Determine the absorption spectrum of a solution of Alprenolol Hydrochloride in ethanol (95) (1 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum wi…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Alprenolol Hydro-chloride, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 28.58 mg of C15H23NO2.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

alprostadil-alfadex
type: ChemicalDrugMonograph
pref label:
  en: Alprostadil Alfadex
  ja: アルプロスタジル アルファデクス
monograph id: JP18-alprostadil-alfadex
publisher: JP
status: Official
version: 18
definition:
  en: Alprostadil Alfadex is a a-cyclodextrin clathrate compound of alprostadil. It contains not less than 2.
appearance:
  en: Alprostadil Alfadex occurs as a white powder. It is freely soluble in water, and practically insoluble in ethanol (95), in ethyl acetate and in diethyl ether. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.02 g of Alprostadil Alfadex in 5 mL of water, add 5 mL of ethyl acetate, shake, and centrifuge. Use the supernatant liquid as the sample solution (1). Separately, to 0.02 g of Alprostadil Alfadex add 5 mL of ethyl acetate, shake, and centrifuge. Use the supernatant liquid as the sample solution (2). Evaporate the solvent from these solutions under reduced pressure, add 2 mL of sulfuric acid to the residue, and shake for 5 minutes: the liquid obtained from the sample solution (1) shows an orange-yellow color, while the liquid obtained from the sample solu-tion (2) does not show that color. Dissolve 0.02 g of Alprostadil Alfadex in 5 mL of water, add 5 mL of ethyl acetate, shake, centrifuge, and evaporate the solvent from the supernatant liquid under reduced pressure. Dissolve the residue in 2 mL of ethanol (95), add 5 mL of 1,3-dinitrobenzene TS, then add 5 mL of a solution of potassium hydroxide in ethanol (95) (17 in 100) under ice-cooling, and allow to stand for 20 minutes in a dark place under ice-cooling: a purple color develops. Dissolve 0.05 g of Alprostadil Alfadex in 1 mL of iodine TS, by heating on a water bath, and allow to stand: a dark blue precipitate is formed. Determine the absorption spectrum of a solution of Alprostadil Alfadex in dilute ethanol (3 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhibits no absorption between 220 nm and 400 nm. Separately, to 10 mL of the solution add 1 mL of potassium hydroxide-ethanol TS, allow to stand for 15 minutes, and determine the absorption spectrum as directed under Ultravi-olet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. D Optical rotation <2.49> [a]20: ＋126 – ＋1389(0.1 g calcu-lated on the anhydrous basis, dilute ethanol, 20 mL, 100 mm). pH <2.54> Dissolve 0.10 g of Alprostadil Alfadex in 20 mL of water: the pH of this solution is between…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Alprostadil Alfadex in 10 mL of water: the solution is col- ‌JP XVIII Official Monographs / Alum Solution 439 orless. Perform the test with this solution as directed under Ultraviolet-visible Spectrophotometry within 30 minutes after preparation of the solution: the absorbance at 450 nm is not larger than 0.10. Prostaglandin A1—Dissolve 0.10 g of Alprostadil Alfadex in 5 mL of water, add exactly 5 mL of the internal standard solution and ethanol (95) to make 15 mL, and use this solution as the sample solution. Separately, dissolve 1.5 mg of prostaglandin A1 in ethanol (95) to make exactly 100 mL. Pipet 3 mL of this solution, add exactly 5 mL of the in-ternal standard solution, 2 mL of ethanol (95) and water to make 15 mL, and use this solution as the standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the operating conditions described in the Assay, and calculate the ratios, QT and QS, of the peak area of prostaglandin A1 to that of the internal standard: QT is not larger than QS. Internal standard solution—A solution of propyl parahy-droxybenzoate in dilute ethanol (1 in 15,000). Related substances—Dissolve 0.10 g of Alprostadil Alfadex in 3 mL of water, add exactly 3 mL of ethyl acetate, shake, centrifuge, and use the supernatant liquid obtained as the sample solution. Separately, dissolve 1.0 mg of prostaglandin A1 in ethyl acetate to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chro-matography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, hexane and acetic acid (100) (10:2:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly a solution of phosphomolybdic acid n-hydrate in eth…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of Alprostadil Alfadex, dissolve in 5 mL of water, add exactly 5 mL of the internal standard solution and water to make 15 mL, and use this solution as the sample solution. Separately, weigh accurately about 3 mg of Alprostadil RS, dissolve in 5 mL of ethanol (95), add exactly 5 mL of the internal standard solu-tion and water to make 15 mL, and use this solution as the standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of alprostadil to that of the internal standard. Amount (mg) of alprostadil (C20H34O5) ＝ MS × QT/QS MS: Amount (mg) of Alprostadil RS taken Internal standard solution—A solution of propyl parahy-droxybenzoate in dilute ethanol (1 in 15,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 205 nm). Column: A stainless steel column about 5 mm in inside diameter and about 15 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of 0.02 mol/L potassium dihy-drogenphosphate and acetonitrile (3:2). Flow rate: Adjust so that the retention time of alprostadil is about 6 minutes. Selection of column: Dissolve about 0.1 g of Alprostadil Alfadex in 5 mL of water, add 5 mL of a solution of prostaglandin A1 in ethanol (95) (3 in 200,000) and 5 mL of the internal standard solution. Proceed with 10 mL of this solution under the above operating conditions, and calculate the resolution. Use a column giving elution of alprostadil, the internal standard and prostaglandin A1 in this order and complete separation of these peaks.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant, at a temperature not exceeding
type: PharmacopoeiaMonograph

alprostadil
type: ChemicalDrugMonograph
pref label:
  en: Alprostadil
  ja: アルプロスタジル
monograph id: JP18-alprostadil
publisher: JP
status: Official
version: 18
molecular formula: C20H34O5
molecular weight: 354.48
definition:
  en: Alprostadil, when dried, contains not less than 97.
appearance:
  en: Alprostadil occurs as white, crystals or crystal-line powder. It is freely soluble in ethanol (99.5) and in tetrahydrofu-ran, slightly soluble in acetonitrile, and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) The absorption spectrum of a solution of Alprostadil in ethanol (99.5) (1 in 100,000) determined as directed under Ultraviolet-visible Spectrophotometry <2.24> shows no absorption between 210 nm and 350 nm. Sepa-rately, to 10 mL of this solution add 1 mL of potassium hy-droxide-ethanol TS, allow to stand for 15 minutes, and de-termine the absorption spectrum in the same way. Compare the spectrum so obtained with the Reference Spectrum or the spectrum of a solution of Alprostadil RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Alprostadil, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum or the spectrum of previously dried Alprostadil RS: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －53 – －619(after drying, 25 mg, tetrahydrofuran, 5 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Related substances—Dissolve 4 mg of Alprostadil in 2 mL of a mixture of acetonitrile for liquid chromatography and water (9:1), and use this solution as the sample solution. Pipet 0.5 mL of the sample solution, and add the mixture of acetonitrile for liquid chromatography and water (9:1) to make exactly 10 mL. Pipet 2 mL of this solution, add the mixture of acetonitrile for liquid chromatography and water (9:1) to make exactly 10 mL, and use this solution as the standard solution. Perform the test with exactly 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the area of the peaks, having the relative retention time of about 0.70 and 1.26 to alprostadil, ob-tained from the sample solution is not larger than 1/2 times the peak area of alprostadil from the standard solution, the area of the peaks, having the relative retention time of about 0.88 and 1.18 to alprostadil, is not larger than the peak area of alprostadil from the standard solution, the area of the peaks other than alprostadil and the peaks mentioned above is not larger than 1/10 times the peak area of alprostadil from the standard solution and the total area of the peaks other than alprostadil is not larger than 2 times the peak area of alprostadil from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 5 times as long as the retention time of alprostadil, beginning after the solvent peak. System suitability— System performance: Proceed as directed in the system suitability in the Assay. Test for required detectability: Measure exactly 2 mL of the standard solution, add the mixture of acetonitrile for liq-uid chromatography and water (9:1) to make exactly 20 mL. Confirm that the peak area of alprost…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 5 mg each of Alprostadil and Alprostadil RS, previously dried, dissolve in exactly 5 mL of the internal standard solution, add a mixture of aceto-nitrile for liquid chromatography and water (9:1) to make 50 mL, and use these solutions as the sample solution and standard solution, respectively. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and calculate the ratios, QT and QS, of the peak area of alprostadil to that of the internal standard. Alprostadil Injection
type: PharmacopoeiaMonograph

alum
type: ChemicalDrugMonograph
pref label:
  en: Alum
  ja: 硫酸アルミニウムカリウム水和物
monograph id: JP18-alum
publisher: JP
status: Official
version: 18
molecular formula: AlK(SO4)2.12H2O
molecular weight: 474.39
definition:
  en: Aluminum Potassium Sulfate Hydrate contains not less than 99.
appearance:
  en: Aluminum Potassium Sulfate Hydrate occurs as colorless or white, crystals or powder. It is odorless. It has a slightly sweet, strongly astringent taste. It is freely soluble in water, and practically insoluble in ethanol (95) and in diethyl ether. A solution of Aluminum Potassium Sulfate Hydrate (1 in 20) is acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: A solution of Aluminum Potassium Sulfate Hydrate (1 in 10) responds to Qualitative Tests <1.09> for aluminum salt, to Qualitative Tests <1.09> (1), (3) and (4) for potassium salt, and to the Qualitative Tests <1.09> (1) and (3) for sulfate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Aluminum Potassium Sulfate Hydrate according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of Aluminum Potassium Sulfate Hydrate according to Method 1, and perform the test according to Method A. Prepare the control solution with 2.0 mL of Standard Iron Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 0.6 g of Aluminum Potassium Sulfate Hydrate, according to Method 1, and perform the test (not more than 3.3 ppm).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 4.5 g of Aluminum Potas-sium Sulfate Hydrate, and dissolve in water to make exactly 200 mL. Take exactly 20 mL of this solution, and add ex-actly 30 mL of 0.05 mol/L disodium dihydrogen ethylene-diamine tetraacetate VS and 20 mL of acetic acid-ammo-nium acetate buffer solution (pH 4.8), boil for 5 minutes, and cool. Add 55 mL of ethanol (95), and titrate <2.50> with 0.05 mol/L zinc acetate VS (indicator: 2 mL of dithizone TS), until the color of the solution changes from light dark green to light red. Perform a blank determination in the same manner. Each mL of 0.05 mol/L disodium dihydorogen ethylenediamine tetraacetate VS ＝ 23.72 mg of AlK(SO4)2.12H2O
storage conditions:
  en: Containers—Tight containers.

amantadine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Amantadine Hydrochloride
  ja: アマンタジン塩酸塩
monograph id: JP18-amantadine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C10H17N.HCl
molecular weight: 187.71
definition:
  en: Amantadine Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Amantadine Hydrochloride occurs as a white crystalline powder. It is odorless, and has a bitter taste. It is very soluble in formic acid, freely soluble in water, in methanol and in ethanol (95), and practically insoluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 0.1 g of Amantadine Hydrochloride add 1 mL of pyridine and 0.1 mL of acetic anhydride, dis-solve by boiling for 1 minute, add 10 mL of dilute hydro-chloric acid, and cool in ice water. Filter the crystals sepa-rated, wash with water, and dry at 1059C for 1 hour: the residue melts <2.60> between 1479C and 1519C. Determine the infrared absorption spectrum of Amantadine Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Amantadine Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Amantadine Hydrochloride in 5 mL of water: the pH of this solution is between 4.0 and 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Amantadine Hydrochloride in 10 mL of water: the solu-tion is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g of Amanta- dine Hydrochloride according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Amantadine Hydrochloride according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.50 g of Amantadine Hydrochloride in 10 mL of water, add 10 mL of sodium hy-droxide TS and 10 mL of chloroform, and shake. Filter the chloroform layer through absorbent cotton with 3 g of anhy-drous sodium sulfate on a funnel, and use the filtrate as the sample solution. Pipet 1 mL of the sample solution, add chloroform to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 2 mL each of the sample solution and standard solution as directed under Gas Chromatography <2.02> according to the follow-ing conditions. Determine each peak area of these solutions by the automatic integration method: each peak area other than amantadine obtained from the sample solution is not larger than 1/3 times the peak area of amantadine from the standard solution, and the total area of each peak is not larger than the peak area of amantadine from the standard solution. Operating conditions— Detector: A hydrogen flame-ionization detector. Column: A glass column about 3 mm in inside diameter and about 2 m in length, packed with siliceous earth for gas chromatography (150 to 180 mm in particle diameter) coated with a mixture (L) of branched hydrocarbon of petroleum hexamethyltetracosane group for gas chromatography and potassium hydroxide at the ratios of 2z and 1z, respec-tively. Column temperature: Inject at a constant temperature of about 1259C, maintain the temperature for 5 minutes, raise at the rate of 59C per minute to 1509C, and ma…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Amantadine Hy-drochloride, previously dried, dissolve in 2 mL of formic acid, add exactly 15 mL of 0.1 mol/L perchloric acid VS, and heat on a water bath for 30 minutes. After cooling, add acetic acid (100) to make 70 mL, and titrate <2.50> the excess perchloric acid with 0.1 mol/L sodium acetate VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 18.77 mg of C10H17N.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

ambenonium-chloride
type: ChemicalDrugMonograph
pref label:
  en: Ambenonium Chloride
  ja: アンベノニウム塩化物
monograph id: JP18-ambenonium-chloride
publisher: JP
status: Official
version: 18
molecular formula: C28H42Cl4N4O2
molecular weight: 608.47
definition:
  en: Ambenonium Chloride contains not less than 98.
appearance:
  en: Ambenonium Chloride occurs as a white pow-der. It is freely soluble in water, in methanol and in acetic acid (100), soluble in ethanol (95), and slightly soluble in acetic anhydride. It is hygroscopic. Melting point: about 2059C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Ambenonium Chloride in methanol (1 in 5000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Ambenonium Chloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Ambenonium Chloride (1 in 100) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Ambenonium Chloride in 10 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Am- benonium Chloride according to Method 4, and perform the test. Use a solution of magnesium nitrate in ethanol (95) (1 in 5). Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.10 g of Ambenonium Chloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add methanol to make exactly 20 mL. Pipet 1 mL of this solu-tion, add methanol to make exactly 10 mL, and use this solu-tion as the standard solution. Perform the test with these so-lutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. De-velop the plate with a mixture of 1-butanol, formic acid and water (12:6:5) to a distance of about 10 cm, and air-dry the plate. Allow the plate to stand in iodine vapor: the spots other than the principal spot obtained from the sample solu-tion are not more intense than the spot from the standard so-lution. Loss on drying <2.41> Not more than 11.5z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Ambenonium Chlo-ride, and dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3). Titrate <2.50> with 0.1 mol/L per-chloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 30.42 mg of C28H42Cl4N4O2
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

amidotrizoic-acid
type: ChemicalDrugMonograph
pref label:
  en: Amidotrizoic Acid
  ja: アミドトリゾ酸
monograph id: JP18-amidotrizoic-acid
publisher: JP
status: Official
version: 18
molecular formula: C11H9I3N2O4
molecular weight: 613.91
definition:
  en: Amidotrizoic Acid, calculated on the dried basis, contains not less than 98.
appearance:
  en: Amidotrizoic Acid occurs as a white crystalline powder. It is odorless. It is slightly soluble in ethanol (95), very slightly soluble in water, and practically insoluble in diethyl ether. It dissolves in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Heat 0.1 g of Amidotrizoic Acid over a flame: a purple gas is evolved. (2) Determine the infrared absorption spectrum of Amidotrizoic Acid as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g ‌446 of Amidotrizoic Acid in 10 mL of 0.2 mol/L sodium hydrox-ide TS: the solution is clear and colorless. Primary aromatic amines—Dissolve 0.20 g of Amidotrizoic Acid in 5 mL of water and 1 mL of sodium hydroxide TS, add 4 mL of a solution of sodium nitrite (1 in 100) and 10 mL of 1 mol/L hydrochloric acid TS, shake, and allow to stand for 2 minutes. Add 5 mL of ammonium amidosulfate TS, shake well, allow to stand for 1 minute, and add 0.4 mL of a solution of 1-naphthol in ethanol (95) (1 in 10), 15 mL of sodium hydroxide TS and water to make exactly 50 mL. Determine the absorbance of this solution at 485 nm as directed under Ultraviolet-visible Spectropho-tometry <2.24> using a solution, prepared in the same man-ner, as the blank: the absorbance is not more than 0.15. Soluble halides—Dissolve 2.5 g of Amidotrizoic Acid in 20 mL of water and 2.5 mL of ammonia TS, add 20 mL of dilute nitric acid and water to make 100 mL, allow to stand for 15 minutes with occasional shaking, and filter. Discard the first 10 mL of the filtrate, transfer the subsequent 25 mL of the filtrate to a Nessler tube, and add ethanol (95) to make 50 mL. Proceed as directed under Chloride Limit Test <1.03> using this solution as the test solution. Prepare the control solution as follows: to 0.10 mL of 0.01 mol/L hydro-chloric acid VS, add 6 mL of dilute nitric acid and water to make 25 mL, then ethanol (95) to make 50 mL. Iodine—Dissolve 0.20 g of Amidotrizoic Acid in 2.0 mL of sodium hydroxide TS, add 2.5 mL of 0.5 mol/L sul-furic acid TS, allow to stand for 10 minutes with occasional shaking, add 5 mL of chloroform, shake well, and allow to stand: the solution is colorless in the chloroform layer. Heavy metals <1.07>—Proceed with 2.0 g of Amidotrizoic Acid according to Method 2, and perform the Amikacin Sulfate
type: PharmacopoeiaMonograph

amikacin-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Amikacin Sulfate
  ja: アミカシン硫酸塩
monograph id: JP18-amikacin-sulfate
publisher: JP
status: Official
version: 18
molecular formula: C22H43N5O13.2H2SO4
molecular weight: 781.76
cas number: 39831-55-5
definition:
  en: Amikacin Sulfate is the sulfate of a derivative of kanamycin. It contains not less than 691 mg (potency) and not more than 791 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Amikacin Sulfate occurs as a white to yellow-white powder. It is very soluble in water, and practically insoluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of Amikacin Sulfate, previously dried, as directed in the potassium bromide disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum or the spectrum of Amikacin Sulfate RS previously dried: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolve 0.1 g each of Amikacin Sulfate and Amika-cin Sulfate RS in 4 mL of water, and use these solutions as the sample solution and standard solution. Perform the test with these solutions as directed under Thin-layer chromatog-raphy <2.03>. Spot 2 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chro-matography. Develop the plate with a mixture of water, ammonia water (28), methanol and tetrahydrofuran (1:1:1:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly ninhydrin-citric acid-acetic acid TS on the plate, and heat at 1009C for 10 minutes: the principal spot obtained from the sample solution and the spot from the standard so-lution show a red-purple color and the same Rf value. A solution of Amikacin Sulfate (1 in 100) responds to Qualitative Tests <1.09> (1) for sulfate. D Optical rotation <2.49> [a]20: ＋76 – ＋849(1 g, water, 100 mL, 100 mm). pH <2.54> Dissolve 1.0 g of Amikacin Sulfate in 100 mL of water: the pH of the solution is between 6.0 and 7.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of ‌JP XVIII Official Monographs / Amikacin Sulfate Injection 447 Amikacin Sulfate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 0.10 g of Amikacin Sulfate in 4 mL of a water, and use this solution as the sam-ple solution. Pipet 1 mL of the sample solution, add water to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer chromatography <2.03>. Spot 2 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of water, ammonia water (28), methanol and tetra-hydrofuran (1:1:1:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly ninhydrin-citric acid-acetic acid TS on the plate, and heat the plate at 1009C for 10 minutes: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 4.0z (1 g, in vacu-um, 609C, 3 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Transfer about 0.5 g of Amidotrizoic Acid, accu-rately weighed, to a saponification flask, dissolve in 40 mL of sodium hydroxide TS, add 1 g of zinc powder, connect to a reflux condenser, boil for 30 minutes, cool, and filter. Wash the flask and the filter paper with 50 mL of water, and combine the washings and the filtrate. Add 5 mL of acetic acid (100) to this solution, and titrate <2.50> with 0.1 mol/L silver nitrate VS until the color of the precipitate changes from yellow to green (indicator: 1 mL of tetrabromophenol-phthalein ethyl ester TS). Each mL of 0.1 mol/L silver nitrate VS ＝ 20.46 mg of C11H9I3N2O4
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

aminophylline-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Aminophylline Hydrate
  ja: アミノフィリン水和物
monograph id: JP18-aminophylline-hydrate
publisher: JP
status: Official
version: 18
appearance:
  en: Aminophylline Hydrate occurs as white to pale yellow, granules or powder. It is odorless or slightly ammo-nia-like odor, and has a bitter taste. It is soluble in water, slightly soluble in methanol, and practically insoluble in ethanol (95) and in diethyl ether. To 1 g of Aminophylline Hydrate add 5 mL of water, and shake: it dissolves almost completely. Separation of crystals begins in 2 to 3 minutes, and these crystals dissolve on the addition of a small amount of ethylenediamine. It is gradually affected by light, and gradually loses ethyl-enediamine in air.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.75 g of Aminophylline Hy-drate in 30 mL of water, and use this solution as the sample solution. To 20 mL of the sample solution add 1 mL of dilute hydrochloric acid: a precipitate is gradually formed. Filter the precipitate, recrystallize from water, and dry at 1059C for 1 hour: the crystals so obtained melt <2.60> between 2719C and 2759C. Dissolve 0.1 g of the crystals obtained in (1) in 50 mL of water, and to 2 mL of this solution add tannic acid TS dropwise: a white precipitate is produced, and this precipi-tate dissolves upon dropwise addition of tannic acid TS. To 0.01 g of the crystals obtained in (1) add 10 drops of hydrogen peroxide TS and 1 drop of hydrochloric acid, and evaporate on a water bath to dryness: the residue shows a yellow-red color. Invert the dish containing the residue over a vessel containing 2 to 3 drops of ammonia TS: the color of the residue changes to red-purple, which is des-troyed on the addition of 2 to 3 drops of sodium hydroxide TS. Dissolve 0.01 g of the crystals obtained in (1) in 5 mL of water, add 3 mL of ammonia-ammonium chloride buffer solution (pH 8.0) and 1 mL of copper (II) sulfate-pyridine TS, and mix. Add 5 mL of chloroform to the mixture, and shake: the chloroform layer develops a green color. To 5 mL of the sample solution obtained in (1) add 2 drops of copper (II) sulfate TS: a purple color develops. Add Amount [mg (potency)] of amikacin (C ＝ MS × HT/HS 22H43N5O13) 1 mL of copper (II) sulfate TS: the color changes to blue, and green precipitates are formed on standing. MS: Amount [mg (potency)] of Amikacin Sulfate RS taken pH <2.54> Dissolve 1.0 g of Aminophylline Hydrate in 25 mL of water: the pH of the solution is between 8.0 and 9.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g ‌JP XVIII Official Monographs / Aminophylline Injection 449 of Aminophylline Hydrate in 10 mL of hot water: the solu-tion is clear and colorless to pale yellow. (2) Heavy metals <1.07>—Proceed with 1.0 g of Aminophylline Hydrate according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Water <2.48> Not more than 7.9z (0.3 g, direct titration). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Theophylline—Weigh accurately about 0.25 g of Aminophylline Hydrate, and dissolve in 50 mL of water and 8 mL of ammonia TS by gentle warming on a water bath. Add exactly 20 mL of 0.1 mol/L silver nitrate VS, warm on a water bath for 15 minutes, allow to stand be-tween 59C and 109C for 20 minutes, collect the precipitate by suction, and wash with three 10-mL portions of water. Combine the filtrate and washings, and add dilute nitric acid to make neutral. Add 3 mL of dilute nitric acid, and titrate <2.50> the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ammonium iron (III) sulfate TS). Perform a blank determination in the same manner. Each mL of 0.1 mol/L silver nitrate VS ＝ 18.02 mg of C7H8N4O2 (2) Ethylenediamine—Weigh accurately about 0.5 g of Aminophylline Hydrate, dissolve in 30 mL of water, and titrate <2.50> with 0.1 mol/L hydrochloric acid VS (indica-tor: 3 drops of bromophenol blue TS). Each mL of 0.1 mol/L hydrochloric acid VS ＝ 3.005 mg of C2H8N2
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

amiodarone-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Amiodarone Hydrochloride
  ja: アミオダロン塩酸塩
monograph id: JP18-amiodarone-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C25H29I2NO3.HCl
molecular weight: 681.77
cas number: 19774-82-4
definition:
  en: Amiodarone Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Amiodarone Hydrochloride occurs as a white to pale yellow-white crystalline powder. It is very soluble in water at 809C, freely soluble in dichloromethane, soluble in methanol, sparingly soluble in ethanol (95), and very slightly soluble in water. Melting point: about 1619C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Amiodarone Hydrochloride in ethanol (95) (1 in 100,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Amiodarone Hydrochloride as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. To 0.1 g of Amiodarone Hydrochloride add 10 mL of water, dissolve by warming at 809C, and cool: the solu-tion responds to Qualitative Tests <1.09> (2) for chloride. pH <2.54> To 1.0 g of Amiodarone Hydrochloride add 20 mL of freshly boiled and cooled water, dissolve by warming at 809C, and cool: the pH of this solution is between 3.2 and 3.8.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Amiodarone Hydrochloride in 10 mL of methanol: the solution is clear, and is not more colored than the following control solutions (1) and (2). Control solution (1): To a mixture of 1.0 mL of Cobalt Chloride CS, 2.4 mL of Iron (III) Chloride CS and 0.4 mL of Copper (II) Sulfate CS, add diluted hydrochloric acid (1 in 40) to make 10.0 mL. To 2.5 mL of this solution add diluted hydrochloric acid (1 in 40) to make 20 mL. Control solution (2): To 3.0 mL of a mixture of 0.2 mL of Cobalt (II) Chloride CS, 9.6 mL of Iron (III) Chloride CS and 0.2 mL of Copper (II) Sulfate CS, add diluted hydro-chloric acid (1 in 40) to make 100 mL. Iodine—To 1.50 g of Amiodarone Hydrochloride add 40 mL of water, dissolve by warming at 809C, cool, add water to make exactly 50 mL, and use this solution as the sample stock solution. Pipet 15 mL of this solution, add exactly 1 mL of 0.1 mol/L hydrochloric acid TS and exactly 1 mL of a solution of potassium iodate (107 in 10,000), add water to make exactly 20 mL, and use this solution as the sample solution. Separately, pipet 15 mL of the sample stock solution, add exactly 1 mL of 0.1 mol/L hydrochloric acid TS, exactly 1 mL of a solution of potassium iodide (441 in 5,000,000) and exactly 1 mL of a solution of potassium iodate (107 in 10,000), add water to make exactly 20 mL, and use this solution as the standard solution. Separately, pipet 15 mL of the sample stock solution, add exactly 1 mL of 0.1 mol/L hydrochloric acid TS, add water to make ex-actly 20 mL, and use this solution as the control solution. Allow the sample solution, standard solution and control so-lution to stand in a dark place for 4 hours. Perform the test with the sample solution and standard solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, using the control solution as the blank: the absorbance of the sam-ple solution at 420 nm is not larger than 1/2 times the absor-bance of the standard solution. …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Amiodarone Hy-drochloride, previously dried, dissolve in 40 mL of a mixture of acetic anhydride and acetic acid (100) (3:1), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 68.18 mg of C25H29I2NO3.HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

amitriptyline-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Amitriptyline Hydrochloride
  ja: アミトリプチリン塩酸塩
monograph id: JP18-amitriptyline-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C20H23N.HCl
molecular weight: 313.86
definition:
  en: Amitriptyline Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Amitriptyline Hydrochloride occurs as color-less crystals or a white to pale yellow crystalline powder. It has a bitter taste and a numbing effect. It is freely soluble in water, in ethanol (95) and in acetic acid (100), soluble in acetic anhydride, and practically in-soluble in diethyl ether. The pH of a solution of 1.0 g of Amitriptyline Hydrochlo-ride in 20 mL of water is between 4.0 and 5.0.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 5 mg of Amitriptyline Hydro-chloride in 3 mL of sulfuric acid: a red color develops. Add 5 drops of potassium dichromate TS to this solution: it turns dark brown. Acidify 1 mL of a solution of Amitriptyline Hydro-chloride (1 in 500) with 0.5 mL of dilute nitric acid, and add 1 drop of silver nitrate TS: a white, opalescent precipitate is produced. Determine the absorption spectrum of a solution of Amitriptyline Hydrochloride (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Amitriptyline Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Amitriptyline Hydrochloride in 20 mL of water: the solu-tion is clear and colorless. (2) Heavy metals <1.07>—Proceed with 2.0 g of Amitrip- tyline Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 10 ppm). Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Amitriptyline Hy-drochloride, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 31.39 mg of C20H23N.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

amlexanox
type: ChemicalDrugMonograph
pref label:
  en: Amlexanox
  ja: アンレキサノクス
monograph id: JP18-amlexanox
publisher: JP
status: Official
version: 18
molecular formula: C16H14N2O4
molecular weight: 298.29
definition:
  en: Amlexanox, when dried, contains not less than 98.
appearance:
  en: Amlexanox occurs as white to yellowish white, crystals or crystalline powder. It is very slightly soluble in ethanol (99.5), and practically insoluble in water. It dissolves in diluted sodium hydroxide TS (1 in 3).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Amlexanox in ethanol (99.5) (1 in 250,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Amlexanox RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Am-lexanox as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Amlexanox RS: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 1.0 g of Amlexanox in 20 mL of water and 10 mL of sodium hydroxide TS, add 15 mL of dilute nitric acid and water to make 50 mL, centri-fuge, and then filter the supernatant liquid. To 25 mL of this filtrate add water to make 50 mL. Perform the test using this solution as the test solution. The control solution consists of 5 mL of sodium hydroxide TS, 7.5 mL of dilute nitric acid, 0.30 mL of 0.01 mol/L hydrochloric acid VS, and water ad-ded to make 50 mL (not more than 0.021z). Heavy metals <1.07>—Proceed with 1.0 g of Amlexa- nox according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—(i) Dissolve 30 mg of Amlexa-nox in 50 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add the mobile phase to make exactly 50 mL. Pipet 1 mL of this solution, add the mobile phase to make exactly 20 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of these solutions by the automatic integration method: the area of the peak other than amlexanox obtained from the sample solution is not larger than 2 times the peak area of amlexanox from the standard solution. Operating conditions— The detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating condi-tions in the Assay. Mobile phase: Dissolve 7.2 g of disodium hydrogen phos-phate dodecahydrate in water to make 1000 mL. Adjust the pH of this solution to 8.0 by adding a solution prepared by dissolving 3.1 g of sodium dihydrogen phosphate dihydrate in 1000 mL of water. To 400 mL of this solution add 600 mL of acetonitrile. Flow rate: To 15 mL of a solution of benzophenone in the mobile phase (3 in 1,000,000) add the…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 30 mg each of Amlexanox and Amlexanox RS, both dried, and dissolve them separately in the mobile phase to make exactly 50 mL. Pipet 5 mL each of these solutions, and add exactly 15 mL of the internal standard solution, and use these solutions as the sample so-lution and the standard solution, respectively. Perform the test with 10 mL each of the sample solution and standard so-lution as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and calculate the ratios, QT and QS, of the peak area of amlexanox to that of the in-ternal standard, respectively. peak other than amlexanox obtained from the sample solu-tion is not larger than 2 times the peak area of amlexanox Amount (mg) of amlexanox (C 16H14N2O4) ＝ M S × QT/QS from the standard solution. Operating conditions— Detector, column, and column temperature: Proceed as directed in the operating conditions in the Assay. MS: Amount (mg) of Amlexanox RS taken Internal standard solution—A solution of 3-nitroaniline in the mobile phase (1 in 4000). ‌JP XVIII Official Monographs / Amlexanox Tablets 455 Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.0 mm in inside diame- 50 mL. Pipet 25 mL of this solution, add exactly 10 mL of the internal standard solution, add the mobile phase to make 100 mL, and use this solution as the standard solution. Then, proceed as directed in the Assay under Amlexanox. ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about Amount (mg) of amlexanox (C ＝ MS × QT/QS × V/200 16H14N2O4) 259C. Mobile phase: Dissolve 17.9 g of disodium hydrogen phos-phate dodecahydrate in water to make 1000 mL. Adjust the pH of this solution to 8.0 by adding a solution prepared by dissolving 7.8 g of sodium dihydrogen phosphate dihydrate in 1000 mL of water. To 760 mL of…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

amlodipine-besilate
type: ChemicalDrugMonograph
pref label:
  en: Amlodipine Besilate
  ja: アムロジピンベシル酸塩
monograph id: JP18-amlodipine-besilate
publisher: JP
status: Official
version: 18
cas number: 111470-99-6
definition:
  en: Amlodipine Besilate contains not less than 98.
appearance:
  en: Amlodipine Besilate occurs as a white to yel-lowish white crystalline powder. It is freely soluble in methanol, sparingly soluble in ethanol (99.5), and slightly soluble in water. A solution of Amlodipine Besilate in methanol (1 in 100) shows no optical rotation. Melting point: about 1989C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Amlodipine Besilate in 0.01 mol/L hydrochloric acid-methanol TS (1 in 40,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Amlodipine Besilate RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Am-lodipine Besilate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Amlodipine Besilate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. To 30 mg of Amlodipine Besilate add 0.1 g of sodium nitrate and 0.1 g of anhydrous sodium carbonate, mix, and gradually ignite. After cooling, dissolve the residue in 2 mL of dilute hydrochloric acid and 10 mL of water, filter if nec-essary, and add barium chloride TS: a white precipitate is formed.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Amlodipine Besilate according to Method 4, and perform the test. Prepare the control solution with 2.5 mL of Stand-ard Lead Solution (not more than 25 ppm). Related substances—Dissolve 0.10 g of Amlodipine Besilate in 50 mL of a mixture of water and acetonitrile (1:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add the mixture of water and acetonitrile (1:1) to make exactly 100 mL. Pipet 3 mL of this solution, add the mixture of water and acetonitrile (1:1) to make exactly 10 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the area of the peak having the relative Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) 0 – 30 80 → 20 20 → 80 30 – 45 Flow rate: 1.0 mL per minute. Time span of measurement: About 3 times as long as the retention time of amlodipine, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 1 mL of the standard solution, and add a mixture of water and acetonitrile (1:1) to make exactly 10 mL. Confirm that the peak area of amlodi-pine obtained with 10 mL of this solution is equivalent to 7 to 13z of that with 10 mL of the standard solution. System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of amlodipine are not less than 70,000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the rela…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 35 mg each of Amlodipine Besilate and Amlodipine Besilate RS (separately determine the water <2.48> using the same manner as Amlodipine Besi-late), dissolve them separately in the mobile phase to make exactly 250 mL. Pipet 5 mL each of these solutions, add ex-actly 5 mL each of the internal standard solution, add the mobile phase to make 25 mL, and use these solutions as the sample solution and standard solution. Perform the test with 20 mL of the sample solution and standard solution as di-rected under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and ‌JP XVIII Official Monographs / Amlodipine Besilate Orally Disintegrating Tablets 457 QS, of the peak area of amlodipine to that of the internal standard. Amount (mg) of amlodipine besilate (C H ClN O .C H O S) lowing conditions, and determine each peak area by the au-tomatic integration method: the area of the peak having the relative retention time of about 0.45 to amlodipine obtained from the sample solution is not larger than the peak area of 20 25 2 5 6 6 3 amlodipine from the standard solution, the area of the peak ＝ MS × QT/QS MS: Amount (mg) of Amlodipine Besilate RS taken, cal-culated on the anhydrous basis Internal standard solution—A solution of isobutyl para-hydroxybenzoate in the mobile phase (3 in 20,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 237 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of methanol and a solution of potassium dihydrogen phosphate (41 in 10,000) (13:7). Flow rate: Adjust so that the retention time of amlodipine is about 8 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above oper…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

ammonia-water
type: ChemicalDrugMonograph
pref label:
  en: Ammonia Water
  ja: アンモニア水
monograph id: JP18-ammonia-water
publisher: JP
status: Official
version: 18
definition:
  en: Ammonia Water contains not less than 9.
appearance:
  en: Ammonia Water occurs as a clear, colorless liquid, having a very pungent, characteristic odor. It is alkaline. Specific gravity d 20: 0.95 – 0.96
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Hold a glass rod moistened with hydro-chloric acid near the surface of Ammonia Water: dense white fumes are produced. (2) Hold moistened red litmus paper near the surface of Ammonia Water: it turns blue.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Residue on evaporation—Evaporate 10.0 mL of Ammonia Water to dryness, and dry the residue at 1059C for 1 hour: the mass of the residue is not more than 2.0 mg. (2) Heavy metals <1.07>—Evaporate 5.0 mL of Ammo- nia Water to dryness on a water bath, add 1 mL of dilute hydrochloric acid to the residue, and evaporate to dryness. Dissolve the residue in 2 mL of dilute acetic acid, add water
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Pipet 5 mL of Ammonia Water, add 25 mL of water, and titrate <2.50> with 0.5 mol/L sulfuric acid VS (in-dicator: 2 drops of methyl red TS). Each mL of 0.5 mol/L sulfuric acid VS ＝ 17.03 mg of NH3
storage conditions:
  en: Containers—Tight containers. Storage—Not exceeding 309C.

amobarbital
type: ChemicalDrugMonograph
pref label:
  en: Amobarbital
  ja: アモバルビタール
monograph id: JP18-amobarbital
publisher: JP
status: Official
version: 18
molecular formula: C11H18N2O3
molecular weight: 226.27
cas number: 57-43-2
definition:
  en: Amobarbital, when dried, contains not less than 99.
appearance:
  en: Amobarbital occurs as white, crystals or crys-talline powder. It is odorless, and has a slightly bitter taste. It is freely soluble in ethanol (95), in acetone and in diethyl ether, sparingly soluble in chloroform, and practically in- soluble in water. It dissolves in sodium hydroxide TS and in sodium car-bonate TS. The pH of a saturated solution of Amobarbital is between 5.0 and 5.6.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Boil 0.2 g of Amobarbital with 10 mL of sodium hydroxide TS: the gas evolved changes moistened red litmus paper to blue. Dissolve 0.05 g of Amobarbital in 2 to 3 drops of am-monia-ammonium chloride buffer solution (pH 10.7) and 5 mL of diluted pyridine (1 in 10). Add 5 mL of chloroform and 0.3 mL of copper (II) sulfate TS to the solution: a red-purple precipitate is produced in the aqueous layer. Shake the mixture: a red-purple color is produced in the chlo-roform layer. To 0.4 g of Amobarbital add 0.1 g of anhydrous sodium carbonate and 4 mL of water, shake, and add a solu-tion of 0.3 g of 4-nitrobenzyl chloride in 7 mL of ethanol (95). Heat the mixture on a water bath for 30 minutes under a reflux condenser, and allow to stand for 1 hour. Filter the crystals produced, wash with 7 mL of sodium hydroxide TS and a small portion of water, recrystallize from ethanol, and dry at 1059C for 30 minutes: the crystals so obtained melt <2.60> between 1689C and 1739C or between 1509C and 1549C.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Amobarbital in 5 mL of sodium hydroxide TS: the solu-tion is clear and colorless. Chloride <1.03>—Dissolve 0.30 g of Amobarbital in 20 mL of acetone, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: take 0.30 mL of 0.01 mol/L hydrochloric acid VS, 20 mL of acetone and 6 mL of dilute nitric acid, and add water to make 50 mL (not more than 0.035z). Sulfate <1.14>—Dissolve 0.40 g of Amobarbital in 20 mL of acetone, and add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solu-tion as the test solution. Prepare the control solution as follows: take 0.40 mL of 0.005 mol/L sulfuric acid VS, 20 mL of acetone, and 1 mL of dilute hydrochloric acid, and add water to make 50 mL (not more than 0.048z). Heavy metals <1.07>—Proceed with 1.0 g of Amobar- bital according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Readily carbonizable substances <1.15>—Perform the test with 0.5 g of Amobarbital. The solution is not more colored than Matching Fluid A. Loss on drying <2.41> Not more than 1.0z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Amobarbital, previ-ously dried, and dissolve in 5 mL of ethanol (95) and 50 mL of chloroform. Titrate <2.50> with 0.1 mol/L potassium hydroxide-ethanol VS until the color of the solution changes from yellow through light blue to purple (indicator: 1 mL of alizarin yellow GG-thymolphthalein TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L potassium hydroxide-ethanol VS ＝ 22.63 mg of C11H18N2O3
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

amosulalol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Amosulalol Hydrochloride
  ja: アモスラロール塩酸塩
monograph id: JP18-amosulalol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C18H24N2O5S.HCl
molecular weight: 416.92
definition:
  en: Amosulalol Hydrochloride contains not less than 98.
appearance:
  en: Amosulalol Hydrochloride occurs as white crystals or a white crystalline powder. It has a bitter taste. It is very soluble in formic acid, freely soluble in metha- nol, and sparingly soluble in water and in ethanol (99.5). It is hygroscopic. A solution of Amosulalol Hydrochloride in methanol (1 in 100) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Amosulalol Hydrochloride (1 in 20,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Amosulalol Hydrochloride as directed in the potassium chlo-ride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Amosulalol Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Place 1.0 g of Amosulalol Hydrochloride in a porcelain crucible, add 1.5 mL of sulfuric acid, cover loosely, and heat gently to car-bonize. After cooling, add 2 mL of nitric acid, heat carefully until white fumes no longer are evolved, and then heat inten-sely to 500 – 6009C to incinerate. After cooling, add 2 mL of hydrochloric acid, proceed according to Method 2, and per-form the test. The control solution, processed in the same manner as the test solution using the same amounts of rea-gents, is prepared by combining 2.0 mL of Standard Lead Solution and water to make 50 mL (not more than 20 ppm). (2) Related substances—Dissolve 0.10 g of Amosulalol Hydrochloride in 20 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample so-lution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area of both solutions by the automatic integration method: the total area of the peaks other than amosulalol obtained from the sample solution is not larger than 2/5 times the peak area of amosulalol from the standard solu-tion. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 272 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 309C. Mobile phase: Dissolve 1.36 g of potassium dihydrogen phosphate in water to make 1000 mL, and adjust to pH 5.7 by adding a solution prepared by dissolving 3.58 g of disodi-um hydrogen phosphate dodecahydrate in water to make 1000 mL. To 670 mL of this solution add 330 mL of aceto-nitrile. Flow rate: Adjust so that the retention time of amosul…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Amosulalol Hydro-chloride, dissolve in 3 mL of formic acid, add 80 mL of a mixture of acetic acid (100) and acetic anhydride (3:2), and titrate <2.50> within 5 minutes with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 41.69 mg of C18H24N2O5S.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

amoxapine
type: ChemicalDrugMonograph
pref label:
  en: Amoxapine
  ja: アモキサピン
monograph id: JP18-amoxapine
publisher: JP
status: Official
version: 18
molecular formula: C17H16ClN3O
molecular weight: 313.78
definition:
  en: Amoxapine, when dried, contains not less than ard solution, add the mobile phase to make 50 mL, and use this solution as the standard solution.
appearance:
  en: Amoxapine occurs as white to light yellow- white, crystals or crystalline powder. It is freely soluble in acetic acid (100), slightly soluble in ethanol (95) and in diethyl ether, and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Amoxapine in 0.1 mol/L hydrochloric acid TS (1 in 50,000) as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption as the same wavelengths. Determine the infrared absorption spectrum of Amoxapine, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Amoxapine as directed under Flame Coloration Test <1.04> (2): a green color appears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Amoxapine according to Method 2, and perform the test. Prepare the control solution with 3.0 mL of Standard Lead Solution (not more than 15 ppm). (2) Related substances—Dissolve 0.5 g of Amoxapine in 10 mL of a mixture of ethanol (95) and acetic acid (100) (9:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add a mixture of ethanol (95) and acetic acid (100) (9:1) to make exactly 10 mL. Pipet 1 mL of this solution, add a mixture of ethanol (95) and acetic acid (100) (9:1) to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethanol (95) and acetic acid (100) (9:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultravio-let light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.4z (1 g, in vacu-um, 609C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Amoxapine, previ- ‌JP XVIII Official Monographs / Amoxicillin Hydrate 463 ously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue to greenish blue (indicator: 2 drops of crystal violet TS). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 15.69 mg of C17H16ClN3O
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

amoxicillin-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Amoxicillin Hydrate
  ja: アモキシシリン水和物
monograph id: JP18-amoxicillin-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C16H19N3O5S.3H2O
molecular weight: 419.45
definition:
  en: Amoxicillin Hydrate contains not less than 950 mg (potency) and not more than 1010 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Amoxicillin Hydrate occurs as white to light yellow-white, crystals or crystalline powder. It is slightly soluble in water and in methanol, and very slightly soluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Amoxicillin Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Amoxicillin RS: both spectra exhibit similar in-tensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋290 – ＋3159(0.1 g calcu-lated on the anhydrous basis, water, 100 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—To 1.0 g of Amoxicillin Hydrate add 2 mL of a solution of magnesium sulfate hepta-hydrate (1 in 4), mix, and heat on a water bath to dryness. Carbonize the residue by gently heating. After cooling, add 1 mL of sulfuric acid, heat carefully, then heat at 500 – 6009C to incinerate. After cooling, add 1 mL of hydrochloric acid to the residue, and heat on a water bath to dryness. Then add 10 mL of water to the residue, and heat on a water bath to dissolve. After cooling, add ammonia TS to adjust the pH to 3 – 4, and add 2 mL of dilute acetic acid. If necessary, filter, wash the residue on the filter with 10 mL of water, transfer the filtrate and washings into a Nessler tube, add water to make 50 mL, and use this solution as the test solu-tion. Prepare the control solution as follows: To 2.0 mL of Standard Lead Solution add 2 mL of a solution of magne-sium sulfate heptahydrate (1 in 4), then proceed in the same manner as for preparation of the test solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Amoxicillin Hydrate according to Method 4, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of Amoxicillin Hydrate in 50 mL of a solution of boric acid (1 in 200), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a solution of boric acid (1 in 200) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions. Determine each peak area of both solutions by the automatic integration method: the area of the peak other than amoxicillin obtained from the sample solution is not larger than the peak area of amoxicillin from the standard solution. Furthermore, the total area of the peaks other than amoxicillin from the sample solution is not larger than 3 times the peak area of am…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Amoxicillin Hydrate and Amoxicillin RS, equivalent to about 30 mg (potency), dissolve each in a solution of boric acid (1 in 200) to make exactly 100 mL, and use these solutions as the sample solu-tion and standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the peak areas, AT and AS, of amoxicillin in each solution. Amount [ mg (potency)] of amoxicillin (C16H19N3O5S) ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Amoxicillin RS taken ‌464 Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 230 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 1.361 g of sodium acetate trihy-drate in 750 mL of water, adjust to pH 4.5 with acetic acid (31), and add water to make 1000 mL. To 950 mL of this so-lution add 50 mL of methanol. Flow rate: Adjust so that the retention time of amoxicillin is about 8 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating conditions, the number of theoretical plates of the peak of amoxicillin is not less than 2500. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of amoxicillin is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

amphotericin-b
type: ChemicalDrugMonograph
pref label:
  en: Amphotericin B
  ja: アムホテリシン B
monograph id: JP18-amphotericin-b
publisher: JP
status: Official
version: 18
molecular formula: C47H73NO17
molecular weight: 924.08
cas number: 1397-89-3
definition:
  en: Amphotericin B is a polyene macrolide substance having antifungal activity produced by the growth of Streptomyces nodosus. dimethylsulfoxide, and add methanol to make 50 mL. To 1 mL of this solution add methanol to make 50 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Amphotericin B RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Purity Amphotericin A—Weigh accurately about 50 mg each of Amphotericin B and Amphotericin B RS, add ex-actly 10 mL each of dimethylsulfoxide to dissolve, and add methanol to make exactly 50 mL. Pipet 4 mL each of these solutions, add methanol to make exactly 50 mL, and use these solutions as the sample solution and standard solution (1), respectively. Separately, weigh accurately about 20 mg of Nystatin RS, add exactly 40 mL of dimethylsulfoxide to dissolve, then add methanol to make exactly 200 mL. Pipet 4 mL of this solution, add methanol to make exactly 50 mL, and use this solution as the standard solution (2). Perform the test with these solutions as directed under Ultraviolet-visible Spectrophotometry <2.24> using a solution obtained in the same manner as the sample solution as the blank, and determine the absorbances at 282 nm and at 304 nm. Calcu-late the amount of amphotericin A by the following equa-tion: not more than 5z for Amphotericin B used for injec-tions, and not more than 15z for Amphotericin B not used for injections. Amount (z) of amphotericin A ＝ MS ×{(ASa1 × AT2) － (ASa2 × AT1)} × 25 MT ×{(ASa1 × ASb2) － (ASa2 × ASb1)} MS: Amount (mg) of Nystatin RS taken MT: Amount (mg) of Amphotericin B taken ASa1: Absorbance at 282 nm of the standard solution (1) ASb1: Absorbance at 282 nm of the standard solution (2) ASa2: Absorbance at 304 nm of the standard solution (1) ASb2: Absorbance a…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Amphotericin A—Weigh accurately about 50 mg each of Amphotericin B and Amphotericin B RS, add ex-actly 10 mL each of dimethylsulfoxide to dissolve, and add methanol to make exactly 50 mL. Pipet 4 mL each of these solutions, add methanol to make exactly 50 mL, and use these solutions as the sample solution and standard solution (1), respectively. Separately, weigh accurately about 20 mg of Nystatin RS, add exactly 40 mL of dimethylsulfoxide to dissolve, then add methanol to make exactly 200 mL. Pipet 4 mL of this solution, add methanol to make exactly 50 mL, and use this solution as the standard solution (2). Perform the test with these solutions as directed under Ultraviolet-visible Spectrophotometry <2.24> using a solution obtained in the same manner as the sample solution as the blank, and determine the absorbances at 282 nm and at 304 nm. Calcu-late the amount of amphotericin A by the following equa-tion: not more than 5z for Amphotericin B used for injec-tions, and not more than 15z for Amphotericin B not used for injections. Amount (z) of amphotericin A ＝ MS ×{(ASa1 × AT2) － (ASa2 × AT1)} × 25 MT ×{(ASa1 × ASb2) － (ASa2 × ASb1)} MS: Amount (mg) of Nystatin RS taken MT: Amount (mg) of Amphotericin B taken ASa1: Absorbance at 282 nm of the standard solution (1) ASb1: Absorbance at 282 nm of the standard solution (2) ASa2: Absorbance at 304 nm of the standard solution (1) ASb2: Absorbance at 304 nm of the standard solution (2) AT1: Absorbance at 282 nm of the sample solution AT2: Absorbance at 304 nm of the sample solution Loss on drying <2.41> Not more than 5.0z (0.1 g, in vacu-um, 609C, 3 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform the test according to the Cylinder-plate method as directed under Microbial Assay for Antibiotics <4.02> according to the following conditions. Test organism—Saccharomyces cerevisiae ATCC 9763 Culture medium—Use the medium 2) under (1) Agar media for seed and base layer. Preparation of cylinder-agar plate—Proceed as di- ‌466‌ rected in 1.5 Preparation of agar base layer plates under the Cylinder plate method, using Petri dish plates not dispensing the agar medium for base layer and dispensing 8.0 mL of the seeded agar medium. Standard solution—Use light-resistant vessels. Weigh accurately an amount of Amphotericin B RS equiva-lent to about 20 mg (potency), dissolve in dimethylsulfoxide to make exactly 20 mL, and use this solution as the standard stock solution. Keep the standard stock solution at 59C or below and use within 24 hours. Take exactly a suitable amount of the standard stock solution before use, and add dimethylsulfoxide to make solutions so that each mL con-tains 200 mg (potency) and 50 mg (potency). Pipet 1 mL each of these solutions, add 0.2 mol/L phosphate buffer solution (pH 10.5) to make exactly 20 mL, and use these solutions as the high concentration standard solution and low concentra-tion standard solution, respectively. Sample solution—Use light-resistant vessels. Weigh accurately an amount of Amphotericin B equivalent to about 20 mg (potency), dissolve in dimethylsulfoxide to make exactly 20 mL, and use this solution as the sample stock so-lution. Take exactly a suitable amount of the sample stock solution, add dimethylsulfoxide to make solutions so that each mL contains 200 mg (potency) and 50 mg (potency). Pipet 1 mL each of these solutions, add 0.2 mol/L phos-phate buffer solution (pH 10.5) to make exactly 20 mL, and use these solutions as the high concentration sample solution and low concentration sample solution, respectively.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant, and in a cold place.
type: PharmacopoeiaMonograph

ampicillin-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Ampicillin Hydrate
  ja: アンピシリン水和物
monograph id: JP18-ampicillin-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C16H19N3O4S.3H2O
molecular weight: 403.45
cas number: 7177-48-2
definition:
  en: Ampicillin Hydrate contains not less than 960 mg (potency) and not more than 1005 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Ampicillin Hydrate occurs as a white to light ＝ MS × QT/QS × 1000 16 19 3 4 yellow-white, crystals or crystalline powder. It is sparingly soluble in water, slightly soluble in metha- MS: Amount [mg (potency)] of Ampicillin RS taken Internal standard solution—A solution of guaifenesin in the mobile phase (1 in 200). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 230 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 5.94 g of diammonium hydrogen phosphate in 850 mL of water, add 100 mL of acetonitrile, adjust the pH to 5.0 with phosphoric acid, and add water to make exactly 1000 mL. Flow rate: Adjust so that the retention time of ampicillin is about 6 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, ampicillin and the internal standard are eluted in this order with the resolution between these peaks being not less than 40. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of ampicillin to that of the internal standard is not more than 1.0z.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Ampicillin Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Ampicillin RS: both spectra exhibit similar in-tensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋280 – ＋3059(0.5 g calcu-lated on the anhydrous basis, water, 100 mL, 100 mm). pH <2.54> The pH of a solution obtained by dissolving 1.0 g of Ampicillin Hydrate in 400 mL of water is between 3.5 and 5.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Ampicillin Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Ampicillin hydrate according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 50 mg of Ampicillin Hydrate in 50 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with ex-actly 10 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and determine each peak area by the automatic integration method: the area of the peak other than ampicillin obtained from the sample so-lution is not larger than the peak area of ampicillin from the standard solution, and the total area of the peaks other than ampicillin from the sample solution is not larger than 2 times the peak area of ampicillin from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 10 times as long as the retention time of ampicillin. JP XVIII Official Monographs / Ampicillin Hydrate 469 System suitability— Test for required detectability: Pipet 1 mL of the standard solution, and add the mobile phase to make exactly 10 mL. Confirm that the peak area of ampicillin obtained with 10 mL of this solution is equivalent to 7 to 13z of that with 10 mL of the standard solution. System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of ampicillin are not less than 5000 and not more than 1.5, respectively. …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Ampicillin Hydrate and Ampicillin RS, equivalent to about 50 mg (potency), dis-solve in a suitable volume of the mobile phase, add exactly 5 mL each of the internal standard solution and the mobile phase to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and calculate the ratios, QT and QS, of the peak area of ampicillin to that of the internal standard. solution. Perform the test with 1 mL each of the sample Amount [ mg (potency)] of ampicillin (C H N O S) solution and standard solution as directed under Gas Chro-matography <2.02> according to the following conditions, ＝ MS × QT/QS × 1000 16 19 3 4 calculate the ratios, QT and QS, of the peak area of N,N-dimethylaniline to that of the internal standard, and calcu-late the amount of N,N-dimethylaniline by the following equation: not more than 20 ppm. Amount (ppm) of N,N-dimethylaniline ＝ MS/MT × QT/QS × 400 MS: Amount (g) of N,N-dimethylaniline taken MT: Amount (g) of Ampicillin Hydrate taken Internal standard solution—A solution of naphthalene in cyclohexane (1 in 20,000). Operating conditions— Detector: A hydrogen flame-ionization detector. Column: A glass column 2.6 mm in inside diameter and 2 m in length, packed with siliceous earth for gas chromatog-raphy (180 – 250 mm in particle diameter) coated with 50z phenyl-50z methyl polysiloxane for gas chromatography at the ratio of 3z. Column temperature: A constant temperature of about 1209C. Carrier gas: Helium. Flow rate: Adjust so that the retention time of N,N-dimethylaniline is about 5 minutes. System suitability— Test for required detectability: Measure exactly 1 mL of the standard stock solution, and add water to make exactly 250 mL. Pipet 1 mL of this solution, add 5 mL of sodium hydroxide TS and exactly 1 mL of the internal standard …
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

ampiroxicam
type: ChemicalDrugMonograph
pref label:
  en: Ampiroxicam
  ja: アンピロキシカム
monograph id: JP18-ampiroxicam
publisher: JP
status: Official
version: 18
molecular formula: C20H21N3O7S
molecular weight: 447.46
definition:
  en: Ampiroxicam, when dried, contains not less than 99.
appearance:
  en: Ampiroxicam occurs as a white to yellowish white crystalline powder. It is freely soluble in acetic acid (100), soluble in aceto-nitrile, very slightly soluble in ethanol (99.5), and practically insoluble in water. A solution of Ampiroxicam in acetonitrile (1 in 20) shows no optical rotation. It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Ampiroxicam in 0.01 mol/L hydrochloric acid-methanol TS (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Am-piroxicam as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. icam from the standard solution. For the area of the peaks, having the relative retention time of about 0.17 and about 0.46 to ampiroxicam, multiply the correction factor, 0.37 and 0.60, respectively. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 3.9 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (4 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of diluted acetic acid (100) (3 in 500), methanol and acetonitrile (5:3:2). Flow rate: Adjust so that the retention time of ampiroxic-am is about 9 minutes. Time span of measurement: About 2 times as long as the retention time of ampiroxicam, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 5 mL of the standard solution, add acetonitrile to make exactly 50 mL. Confirm that the peak area of ampiroxicam obtained with 10 mL of this solution is equivalent to 7 to 13z of that with 10 mL of the standard solution. System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of ampiroxicam are not less than 3000 and not more than 2.0, respectively. System repea…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Ampiroxicam according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead solution (not more than 20 ppm). (2) Related substances—Dissolve 20 mg of Ampiroxicam in 50 mL of acetonitrile, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add acetonitrile to make exactly 200 mL, and use this solution as the stand-ard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the area of the peak, having a relative retention time of about 0.17 to ampiroxicam, obtained from the sample solution is not larger than 1/2 times the peak area of ampiroxicam from the standard solution, the area of the peak other than ampiroxicam and the peak mentioned above from the sample solution is not larger than 2/5 times the peak area of ampiroxicam from the standard solution, and the total area of the peaks other than ampiroxicam from the sample solution is not larger than the peak area of ampirox-
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.22 g of Ampiroxicam, previously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 44.75 mg of C H N O S 20 21 3 7 Purity (1) Heavy metals <1.07>—Proceed with 1.0 g of Ampiroxicam according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead solution (not more than 20 ppm). (2) Related substances—Dissolve 20 mg of Ampiroxicam in 50 mL of acetonitrile, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add acetonitrile to make exactly 200 mL, and use this solution as the stand-ard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the area of the peak, having a relative retention time of about 0.17 to ampiroxicam, obtained from the sample solution is not larger than 1/2 times the peak area of ampiroxicam from the standard solution, the area of the peak other than ampiroxicam and the peak mentioned above from the sample solution is not larger than 2/5 times the peak area of ampiroxicam from the standard solution, and the total area of the peaks other than ampiroxicam from the sample solution is not larger than the peak area of ampirox-
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

amyl-nitrite
type: ChemicalDrugMonograph
pref label:
  en: Amyl Nitrite
  ja: 亜硝酸アミル
monograph id: JP18-amyl-nitrite
publisher: JP
status: Official
version: 18
molecular formula: C5H11NO2
molecular weight: 117.15
definition:
  en: Amyl Nitrite is the nitrous acid ester of 3-methyl-butanol-1 and contains a small quantity of 2-methyl-butanol-1 and the nitrous acid esters of other homo-logues.
appearance:
  en: Amyl Nitrite is a clear, light yellow-liquid, and has a characteristic, fruity odor. It is miscible with ethanol (95), and with diethyl ether. It is practically insoluble in water. It is affected by light and by heat. It is volatile at ordinary temperature and flammable even at a low temperature. Boiling point: about 979C
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared spectrum of Amyl Nitrite as directed in the liquid film method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi-ties of absorption at the same wave numbers. Specific gravity <2.56> d 20: 0.871 – 0.880
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—To 5 mL of Amyl Nitrite add a mix-ture of 1.0 mL of 1 mol/L sodium hydroxide VS, 10 mL of water and 1 drop of phenolphthalein TS, shake, and allow to stand for 1 minute: the light red color of the water layer does not disappear. Water—Allow 2.0 mL of Amyl Nitrite to stand in ice water: no turbidity is produced. Aldehyde—To 3 mL of a mixture of equal volumes of silver nitrate TS and aldehyde free-ethanol add ammonia TS dropwise until the precipitate first formed is redissolved. Add 1.0 mL of Amyl Nitrite, and warm between 609C and 709C for 1 minute: a brown to black color is not produced. Residue on evaporation—Evaporate 10.0 mL of ‌JP XVIII Official Monographs / Antipyrine 475‌ Amyl Nitrite on a water bath in a draft chamber, carefully protecting from flame, and dry the residue at 1059C for 1 hour: the mass of the residue is not more than 1.0 mg.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately a volumetric flask containing 10 mL of ethanol (95), add about 0.5 g of Amyl Nitrite, and weigh accurately again. Add exactly 25 mL of 0.1 mol/L silver nitrate VS, then add 15 mL of potassium chlorate solu-tion (1 in 20) and 10 mL of dilute nitric acid, stopper the flask immediately, and shake it vigorously for 5 minutes. Dilute with water to make exactly 100 mL, shake, and filter through dry filter paper. Discard the first 20 mL of the fil-trate, measure exactly 50 mL of the subsequent filtrate, and titrate <2.50> the excess silver nitrate with 0.1 mol/L ammo-nium thiocyanate VS (indicator: 2 mL of ammonium iron (III) sulfate TS). Perform a blank determination in the same manner. Each mL of 0.1 mol/L silver nitrate VS ＝ 35.15 mg of C5H11NO2 ‌Containers and storage Containers—Hermetic containers not exceeding 10–ml capacity. Storage—Light-resistant, in a cold place, and remote from fire. Dental Antiformin Dental Sodium Hypochlorite Solution

anesthamine-benzocaine
type: ChemicalDrugMonograph
pref label:
  en: Anesthamine Benzocaine
  ja: アミノ安息香酸エチル
monograph id: JP18-anesthamine-benzocaine
publisher: JP
status: Official
version: 18
molecular formula: C9H11NO2
molecular weight: 165.19
appearance:
  en: Ethyl Aminobenzoate occurs as white, crystals or crystalline powder. It is odorless. It has a slightly bitter taste, numbing the tongue. It is freely soluble in ethanol (95) and in diethyl ether, and very slightly soluble in water. It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 10 mg of Ethyl Aminobenzo-ate in 1 mL of dilute hydrochloric acid and 4 mL of water. This solution responds to Qualitative Tests <1.09> for prima-ry aromatic amines. Dissolve 0.1 g of Ethyl Aminobenzoate in 5 mL of water with the aid of dilute hydrochloric acid added drop-wise, and add iodine TS dropwise: a brown precipitate is produced. Warm 50 mg of Ethyl Aminobenzoate with 2 drops of acetic acid (31) and 5 drops of sulfuric acid: the odor of ethyl acetate is perceptible.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—Dissolve 1.0 g of Ethyl Aminobenzo-ate in 10 mL of neutralized ethanol, and add 10 mL of water, 2 drops of phenolphthalein TS and 0.50 mL of 0.01 mol/L sodium hydroxide VS: a red color is produced. Chloride—Dissolve 0.20 g of Ethyl Aminobenzoate in 5 mL of ethanol (95), add 2 to 3 drops each of dilute nitric acid and of silver nitrate TS: no change occurs immediately. Heavy metals <1.07>—Dissolve 2.0 g of Ethyl Amino- benzoate in 20 mL of ethanol (95), add 2 mL of dilute acetic acid and ethanol (95) to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of Standard Lead Solution add 2 mL of dilute acetic acid and sufficient ethanol (95) to make 50 mL (not more than 10 ppm). Readily carbonizable substances <1.15>—Perform the test with 0.5 g of Ethyl Aminobenzoate: the solution has no more color than Matching Fluid A. Loss on drying <2.41> Not more than 1.0z (1 g, silica gel, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of Ethyl Aminoben-zoate, previously dried, dissolve in 10 mL of hydrochloric acid and 70 mL of water, add 10 mL of a solution of potas-sium bromide (3 in 10), and cool to a temperature below 159C. Then titrate <2.50> with 0.1 mol/L sodium nitrite VS by the potentiometric titration or the amperometric titration. Each mL of 0.1 mol/L sodium nitrite VS ＝ 16.52 mg of C9H11NO2
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

anesthetic-ether
type: ChemicalDrugMonograph
pref label:
  en: Anesthetic Ether
  ja: 麻酔用エーテル
monograph id: JP18-anesthetic-ether
publisher: JP
status: Official
version: 18
molecular formula: C4H10O
molecular weight: 74.12
definition:
  en: Anesthetic Ether contains not less than 96z and not more than 98z (by specific gravity) of ether (C4H10O).
appearance:
  en: Anesthetic Ether occurs as a colorless, clear, mobile liquid, having a characteristic odor. It is miscible with ethanol (95). It is soluble in water. It is highly volatile and flammable. It is slowly oxidized by the action of air and light, with the formation of peroxides. Its vapor, when mixed with air and ignited, may explode violently. Boiling point: 35 – 379C Specific gravity <2.56> d 20: 0.718 – 0.721
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Foreign odor—Place 10 mL of Anesthetic Ether in an evaporating dish, and allow it to evaporate spon-taneously to a volume of about 1 mL: no foreign odor is per-ceptible. Drop this residue onto a piece of clean, odorless filter paper to evaporate the ether: no foreign odor is percep-tible. Acidity—Place 10 mL of diluted ethanol (95) (4 in 5) and 0.5 mL of phenolphthalein TS in a 50-mL glass-stoppered flask, and add 0.02 mol/L sodium hydroxide VS dropwise to produce a red color which persists after shaking for 30 seconds. Add 25 mL of Anesthetic Ether, stopper the flask, shake gently, and add 0.40 mL of 0.02 mol/L sodium hydroxide VS with shaking: a red color develops. Aldehyde—To 100 mL of water in a 200-mL glass-stoppered flask add 10 mL of Anesthetic Ether and 1 mL of a solution of sodium hydrogen sulfite (1 in 1000), stopper tightly, shake vigorously for 10 seconds, and allow the mix-ture to stand in a cool place for 30 minutes, protected from light. Add 2 mL of starch TS, and add dropwise 0.01 mol/L iodine VS until a pale blue color develops. Shake with about 2 g of sodium hydrogen carbonate to decolorize the solution, and add 1 mL of diluted 0.01 mol/L iodine VS (9 in 40): a blue color develops. Keep the temperature of the solution below 189C during the procedure. Peroxide—Place 10 mL of Anesthetic Ether in a Nessler tube, add 1 mL of a freshly prepared solution of po-tassium iodide (1 in 10), shake occasionally for 1 hour, pro-tecting from light, then add 1 mL of starch TS, and shake well: no color is produced and in the aqueous layer and in the ether layer. Residue on evaporation—Evaporate 50 mL of Anesthetic Ether, and dry the residue at 1059C for 1 hour: the mass of the residue is not more than 1.0 mg.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

anhydrous-ampicillin
type: ChemicalDrugMonograph
pref label:
  en: Anhydrous Ampicillin
  ja: 無水アンピシリン
monograph id: JP18-anhydrous-ampicillin
publisher: JP
status: Official
version: 18
molecular formula: C16H19N3O4S
molecular weight: 349.4
cas number: 69-53-4
definition:
  en: Anhydrous Ampicillin contains not less than 960 mg (potency) and not more than 1005 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Anhydrous Ampicillin occurs as white to light yellow-white, crystals or crystalline powder. It is sparingly soluble in water, slightly soluble in metha-nol, very slightly soluble in ethanol (95), and practically in-soluble in acetonitrile.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Anhydrous Ampicillin as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋280 – ＋3059(0.5 g calcu-lated on the anhydrous basis, water, 100 mL, 100 mm). pH <2.54> The pH of a solution obtained by dissolving 1.0 g of Anhydrous Ampicillin in 100 mL of water is be-tween 4.0 and 5.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Anhydrous Ampicillin according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Anhydrous Ampicillin according to Method 3, and per-form the test (not more than 2 ppm). Related substances—Dissolve 0.05 g of Anhydrous Ampicillin in the mobile phase to make 50 mL, and use this solution as the sample solution. Pipet 1 mL of the sample so-lution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the area of each peak other than ampicillin obtained from the sample solution is not larger than the peak area of ampicillin from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: As long as about 10 times of ‌468 the retention time of ampicillin. System suitability— System performance, and system repeatability: Proceed as directed in the system suitability in the Assay. Test for required detectability: To exactly 1 mL of the standard solution add the mobile phase to make exactly 10 mL. Confirm that the peak area of ampicillin obtained with 10 mL of this solution is equivalent to 7 to 13z of that with 10 mL of the standard solution. Water <2.48> Not more than 2.0z (2.5 g, volumetric titra-tion, direct titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Anhydrous Ampicil-lin and Ampicillin RS, equivalent to about 50 mg (potency), add exactly 5 mL each of the internal standard solution and the mobile phase to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of ampicillin to that of the internal standard. Ampicillin Hydrate
type: PharmacopoeiaMonograph

anhydrous-caffeine
type: ChemicalDrugMonograph
pref label:
  en: Anhydrous Caffeine
  ja: 無水カフェイン
monograph id: JP18-anhydrous-caffeine
publisher: JP
status: Official
version: 18
molecular formula: C8H10N4O2
molecular weight: 194.19
definition:
  en: Anhydrous Caffeine, when dried, contains not less than 98.
appearance:
  en: Anhydrous Caffeine occurs as white, crystals or powder. It is odorless, and has a bitter taste. It is freely soluble in chloroform, sparingly soluble in water, in acetic acid (100) and in acetic anhydride, and slightly soluble in ethanol (95) and in diethyl ether. The pH of a solution of 1.0 g of Anhydrous Caffeine in 100 mL of water is between 5.5 and 6.5.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2 mL of a solution of Anhydrous Caffeine (1 in 500) add tannic acid TS dropwise: a white ‌JP XVIII Official Monographs / Caffeine Hydrate 589 precipitate, which dissolves upon the dropwise addition of tannic acid TS, is produced. To 0.01 g of Anhydrous Caffeine add 10 drops of hydrogen peroxide TS and 1 drop of hydrochloric acid, and evaporate on a water bath to dryness: the residue acquires a yellow-red color. Invert the residue over a vessel containing 2 to 3 drops of ammonia TS: the color turns red-purple, and disappears upon the addition of 2 to 3 drops of sodium hy-droxide TS. Dissolve 0.01 g of Anhydrous Caffeine in water to make 50 mL. To 5 mL of this solution add 3 mL of diluted acetic acid (31) (3 in 100) and 5 mL of pyridine (1 in 10), mix, add 2 mL of diluted sodium hypochlorite TS (1 in 5), and allow to stand for 1 minute. Add 2 mL of sodium thio-sulfate TS and 5 mL of sodium hydroxide TS to the solution: a yellow color develops.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 2.0 g of Anhydrous Caffeine in 80 mL of hot water, cool rapidly to 209C, add water to make 100 mL, and use this solution as the sample solution. To 40 mL of the sample solution add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.25 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.011z). Sulfate <1.14>—To 40 mL of the sample solution ob- tained in (1) add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not more than 0.024z). Heavy metals <1.07>—Proceed with 2.0 g of Anhy-drous Caffeine according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 0.10 g of Anhydrous Caffeine in 10 mL of chloroform, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add chloroform to make exactly 100 mL. Pipet 1 mL of this solution, add chloroform to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform and ethanol (95) (9:1) to a dis-tance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solu-tion. Readily carbonizable substances <1.15>—Perform the test using 0.5 g of Anhydrous Caffeine: the solution is not more colored than Matching Fluid D. Loss on drying <2.41> Not more than 0.5z (1 g, 809C, 4 hours). Residue on…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Anhydrous Caffeine, previously dried, dissolve in 70 mL of a mixture of acetic anhydride and acetic acid (100) (6:1), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the solution changes from purple through green to yellow (indicator: 3 drops of crystal violet TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 19.42 mg of C8H10N4O2
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

anhydrous-citric-acid
type: ChemicalDrugMonograph
pref label:
  en: Anhydrous Citric Acid
  ja: 無水クエン酸
monograph id: JP18-anhydrous-citric-acid
publisher: JP
status: Official
version: 18
molecular formula: C6H8O7
molecular weight: 192.12
definition:
  en: Anhydrous Citric Acid contains not less than 99.
appearance:
  en: Anhydrous Citric Acid occurs as colorless crystals, white granules or crystalline powder. It is very soluble in water, and freely soluble in ethanol (99.5).◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Anhydrous Citric Acid, previously dried at 1059C for 2 hours, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 2.0 g of Anhydrous Citric Acid in water to make 10 mL: the solu-tion is clear and colorless or has no more color than the fol-lowing control solutions (1), (2) or (3). Control solution (1): To 1.5 mL of Cobalt (II) Chloride CS and 6.0 mL of Iron (III) Chloride CS add diluted dilute hydrochloric acid (1 in 10) to make 1000 mL. Control solution (2): To 2.5 mL of Cobalt (II) Chloride CS, 6.0 mL of Iron (III) Chloride CS and 1.0 mL of Copper (II) Sulfate CS add diluted dilute hydrochloric acid (1 in 10) to make 1000 mL. Control solution (3): To 0.15 mL of Cobalt (II) Chloride CS, 7.2 mL of Iron (III) Chloride CS and 0.15 mL of Cop-per (II) Sulfate CS add diluted dilute hydrochloric acid (1 in 10) to make 1000 mL. Sulfates—Dissolve 2.0 g of Anhydrous Citric Acid in water to make 30 mL, and use this solution as the sample so-lution. Separately, dissolve 0.181 g of potassium sulfate in diluted ethanol (3 in 10) to make exactly 500 mL. Pipet 5 mL of this solution, and add diluted ethanol (3 in 10) to make exactly 100 mL. To 4.5 mL of this solution add 3 mL of a so-lution of barium chloride dihydrate (1 in 4), shake, and allow to stand for 1 minute. To 2.5 mL of this solution add 15 mL of the sample solution and 0.5 mL of acetic acid (31), and allow to stand for 5 minutes: the solution has no more turbidity than the following control solution (not more than 150 ppm). Control solution: Dissolve 0.181 g of potassium sulfate in water to make exactly 500 mL. Pipet 5 mL of this solution, add water to make exactly 100 mL, and proceed in the same manner as above using this solution instead of the sample so-lution. ‌JP XVIII Official Monographs / Citric Acid Hydrate 769 Oxalic acid—Dissolve 0.80 g of Anhydrous Citric Acid in 4 mL of water, add 3 mL of hydrochloric acid and 1 g of zinc, and boil for 1 minute. After allowing to stand for 2 minutes, take the supernatant liquid, add 0.25 mL of a solution of phenylhydrazinium chloride (1 in 100)…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.55 g of Anhydrous Citric Acid, dissolve in 50 mL of water, and titrate with 1 mol/L sodium hydroxide VS (indicator: 1 drop of phenolphthalein TS). Each mL of 1 mol/L sodium hydroxide VS ＝ 64.04 mg of C6H8O7 ◆Containers and storage Containers—Tight containers.◆ Citric Acid Hydrate
type: PharmacopoeiaMonograph

anhydrous-lactose
type: ChemicalDrugMonograph
pref label:
  en: Anhydrous Lactose
  ja: 無水乳糖
monograph id: JP18-anhydrous-lactose
publisher: JP
status: Official
version: 18
appearance:
  en: Anhydrous Lactose occurs as white, crystals or powder. It is freely soluble in water, and practically insoluble in ethanol (99.5).◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Anhydrous Lactose, previously dried, as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of Anhydrous Lactose for Identification RS: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋54.4 – ＋55.99 Weigh ac-curately about 10 g of Anhydrous Lactose, calculated on the anhydrous basis, dissolve in 80 mL of water warmed to 509C, and add 0.2 mL of ammonia TS after cooling. After standing for 30 minutes, add water to make exactly 100 mL, and determine the optical rotation of this solution in a 100-mm cell.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Anhydrous Lactose in 10 mL of boiling water, and allow to cool: the solution is clear, and colorless or nearly colorless and has no more color than the following control solution. Determine the absorbance at 400 nm of this solution as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, ‌1234 using water as the control solution: not more than 0.04. Control solution: To a mixture of 2.5 mL of Cobalt (II) Chloride CS, 6.0 mL of Iron (III) Chloride CS and 1.0 mL of Copper (II) Sulfate CS, add diluted dilute hydrochloric acid (1 in 10) to make 1000 mL. Acidity or alkalinity—Dissolve 6 g of Anhydrous Lactose by heating in 25 mL of freshly boiled and cooled water, and after cooling, add 0.3 mL of phenolphthalein TS: the solution is colorless, and not more than 0.4 mL of 0.1 mol/L sodium hydroxide VS is required to produce a pink or red color. (3) Heavy metals <1.07>—Proceed with 4.0 g of Anhy- drous Lactose according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 5 ppm).◇ Proteins and light absorbing substances—Dissolve 1.0 g of Anhydrous Lactose in water to make 100 mL, and use this solution as the sample solution. Determine the ab-sorbances of the sample solution as directed under Ultravio-let-visible Spectrophotometry <2.24>, using water as the con-trol solution: not more than 0.25 at between 210 nm and 220 nm, and not more than 0.07 at between 270 nm and 300 nm. Loss on drying <2.41> Not more than 0.5z (1 g, 809C, 2 hours). Water <2.48> Not more than 1.0z (1 g, volumetric titra-tion, direct titration. Use a mixture of methanol for water determination and formamide for water determination (2:1) instead of methanol for water determination). Residue on ignition <2.44> Not more than 0.1z (1 g). Microbial limit <4.05> The acceptance criteria of TAMC and TYMC are 102 CFU/g and 5 × 101 CFU/g, respectively, and ◇Salmonella and◇ Escherichia coli ar…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 3 g of L-Lactic Acid, trans-fer in a conical flask, add accurately measured 40 mL of 1 mol/L sodium hydroxide VS, invert a watch glass over the flask, and heat on a water bath for 10 minutes. Titrate <2.50> the excess sodium hydroxide with 0.5 mol/L sulfuric acid VS immediately (indicator: 2 drops of phenolphthalein TS). Per-form a blank determination in the same manner. Each mL of 1 mol/L sodium hydroxide VS ＝ 90.08 mg of C3H6O3
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

apilac
type: ChemicalDrugMonograph
pref label:
  en: Apilac
  ja: ローヤルゼリー
monograph id: JP18-apilac
publisher: JP
status: Official
version: 18
appearance:
  en: Slightly viscous liquid or powder, milky white to light yellow in color. Odor, characteristic; taste, astrin-gent and acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To a portion of Royal Jelly, equivalent to 0.2 g of dried substance, add 5 mL of water, 1 mL of dilute hydrochloric acid and 10 mL of diethyl ether, shake for 15 minutes, and centrifuge. Take the diethyl ether layer, evapo-rate the solvent under low pressure (in vacuo), dissolve the residue in 5 mL of methanol, and use this solution as the sample solution. Separately, dissolve 2 mg of 10-hydroxy-2-(E)-decenoic acid for thin-layer chromatography in 1 mL of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 20 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography, de-velop the plate with a mixture of 1-propanol and ammonia solution (28) (7:3) to a distance of about 7 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot obtained from the sample solution has the same color tone and Rf value with the spot from the stand-ard solution.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with a portion of Royal Jelly, equivalent to 1.0 g of the dried substance, according to Method 3, and perform the test. Prepare the control solution with 3.0 mL of Standard Lead Solution (not more than 30 ppm). (2) Arsenic <1.11>—Prepare the test solution with an amount of Royal Jelly, equivalent to 0.40 g of the dried sub-stance according to Method 3, and perform the test (not more than 5 ppm). Loss on drying <5.01> The slightly viscous liquid: Not less than 57.0z and not more than 77.0z (6 hours). The powder: Not less than 7.0z and not more than 13.0z (6 hours). Total ash <5.01> Not more than 4.0z, calculated on the dried basis. Acid-insoluble ash <5.01> Not more than 0.5z, calculated on the dried basis.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately a portion of Royal Jelly, equiva-lent to 0.2 g of the dried substance, add 20 mL of methanol, sonicate for 30 minutes, and add methanol to make exactly 50 mL. Centrifuge this solution, pipet 2 mL of the superna-tant liquid, add exactly 2 mL of the internal standard solu-tion, then add 25 mL of water and methanol to make 50 mL, and use this solution as the sample solution. Separately, weigh accurately about 10 mg of 10-hydroxy-2-(E)-decenoic acid for assay, dissolve in methanol to make exactly 100 mL. Pipet 3 mL of this solution, add exactly 2 mL of the internal standard solution, then add 25 mL of water and methanol to make 50 mL, and use this solution as the standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of 10-hydroxy-2-(E)-decenoic acid to that of the internal standard. Amount (mg) of 10-hydroxy-2-(E)-decenoic acid ＝ MS × QT/QS × 3/4 MS: Amount (mg) of 10-hydroxy-2-(E)-decenoic acid for assay taken Internal standard solution—A solution of propyl parahy-droxybenzoate in methanol (1 in 5000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 215 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 509C. Mobile phase: A mixture of water, methanol for liquid chromatography and phosphoric acid (550:450:1). Flow rate: Adjust so that the retention time of 10-hydroxy-2-(E)-decenoic acid is about 10 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, 10-hydroxy-2-(E)-decenoic acid and the internal standard are eluted in this order with the resolution between thes…
storage conditions:
  en: Containers—Tight containers. Storage—At not exceeding 109C.

apricot-kernel-water
type: ChemicalDrugMonograph
pref label:
  en: Apricot Kernel Water
  ja: キョウニン水
monograph id: JP18-apricot-kernel-water
publisher: JP
status: Official
version: 18
definition:
  en: Apricot Kernel Water contains not less than 0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfate <1.14>—Add a few drops of 0.1 mol/L sodium hydroxide VS to 5.0 mL of Apricot Kernel Water to make slightly alkaline, evaporate on a water bath to dryness, and ignite between 4509C and 5509C. Dissolve the residue in 1.0 mL of dilute hydrochloric acid, and add water to make 50 mL. Perform the test using this solution as the test solu-tion. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.005z). Heavy metals <1.07>—Evaporate 50 mL of Apricot Kernel Water on a water bath to dryness, ignite between 4509C and 5509C, dissolve the residue in 5 mL of dilute acetic acid with warming, add water to make exactly 50 mL, and filter. Remove the first 10 mL of the filtrate, dilute the subsequent 20 mL to 50 mL with water, and perform the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of Standard Lead Solution add 2 mL of dilute acetic acid and water to make 50 mL (not more than 1 ppm). Free hydrogen cyanide—To 10 mL of Apricot Kernel Water add 0.8 mL of 0.1 mol/L silver nitrate VS and 2 to 3 drops of nitric acid at 159C, filter, and add 0.1 mol/L silver nitrate VS to the filtrate: no change occurs. Residue on evaporation—Evaporate 5.0 mL of Apricot Kernel Water to dryness, and dry the residue at 1059C for 1 hour: the mass of the residue is not more than 1.0 mg.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Measure exactly 25 mL of Apricot Kernel Water, add 100 mL of water, 2 mL of potassium iodide TS and 1 mL of ammonia TS, and titrate <2.50> with 0.1 mol/L silver nitrate VS until a yellow turbidity persists. Each mL of 0.1 mol/L silver nitrate VS ＝ 5.405 mg of HCN
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.

aprindine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Aprindine Hydrochloride
  ja: アプリンジン塩酸塩
monograph id: JP18-aprindine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C22H30N2.HCl
molecular weight: 358.95
definition:
  en: Aprindine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Aprindine Hydrochloride occurs as a white to pale yellow-white crystalline powder. It has a bitter taste, numbing the tongue. It is very soluble in water, in methanol and in acetic acid (100), and freely soluble in ethanol (99.5). It gradually turns brown on exposure to light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 10 mg of Aprindine Hydro-chloride in a solution of hydrochloric acid in diluted ethanol (1 in 2) (1 in 125) to make 50 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Aprindine Hydrochloride as directed in the potassium chlo-ride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. To 5 mL of a solution of Aprindine Hydrochloride (1 in 50) add 1 mL of dilute nitric acid: this solution re-sponds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Aprindine Hydrochloride in 50 mL of water: the pH of the solution is between 6.4 and 7.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Aprindine Hydrochloride in 10 mL of methanol: the solu-tion is clear, and its absorbance at 420 nm determined as di-rected under Ultraviolet-visible Spectrophotometry <2.24> is not more than 0.10. Heavy metals <1.07>—Proceed with 1.0 g of Aprin- dine Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 25 mg of Aprindine Hydrochloride in 10 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample so-lution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the area of the peak other than aprindine obtained from the sample solution is not larger than 1/10 times the peak area of aprindine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 3.40 g of potassium dihydrogen phosphate in 500 mL of water, and adjust the pH to 3.0 with hydrochloric acid. To 500 mL of this solution add 500 mL of acetonitrile. Flow rate: Adjust so that the retention time of aprindine is about 6 minutes. Time span of measurement: About 4 times as long as the retention time of aprindine. System suitability— Test for required detectability: Pipet 1 mL of the standard solution, and add the mobile phase to make exactly 10 mL. Confirm that the peak area of aprindine obtained wit…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Aprindine Hydro-chloride, previously dried, dissolve in 80 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 35.90 mg of C22H30N2.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

arbekacin-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Arbekacin Sulfate
  ja: アルベカシン硫酸塩
monograph id: JP18-arbekacin-sulfate
publisher: JP
status: Official
version: 18
definition:
  en: Arbekacin Sulfate is the sulfate of a derivative of dibekacin. It contains not less than 670 mg (potency) and not more than 750 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Arbekacin Sulfate occurs as a white powder. It is very soluble in water, and practically insoluble in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 10 mg each of Arbekacin Sul-fate and Arbekacin Sulfate RS in 1 mL of water, and use these solutions as the sample solution and standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 2 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ammonia solution (28), methanol, chloroform and ethanol (95) (7:6:4:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly 0.2z ninhydrin-water saturated 1-butanol TS on the plate, and heat the plate at 1009C for 10 minutes: the principal spot obtained from the sample solu-tion and the spot from the standard solution are purple-brown in color and their Rf values are the same. (2) A solution of Arbekacin Sulfate (1 in 50) responds to Qualitative Tests <1.09> (1) for sulfate. D Optical rotation <2.49> [a]20: ＋69 – ＋799 (0.25 g after drying, water, 25 mL, 100 mm). pH <2.54> The pH of a solution obtained by dissolving 0.75 g of Arbekacin Sulfate in 10 mL of water is between 6.0 and 8.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution obtained by dissolving 1.0 g of Arbekacin Sulfate in 5 mL of water is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g of Arbeka- cin Sulfate according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Dibekacin—Weigh accurately about 20 mg of Ar-bekacin Sulfate, add exactly 10 mL of the internal standard solution to dissolve, add water to make 20 mL, and use this solution as the sample solution. Separately, weigh accurately an amount of Dibekacin Sulfate RS, equivalent to about 10 mg (potency), and dissolve in water to make exactly 50 mL. Pipet 5 mL of this solution, add exactly 10 mL of the inter-nal standard solution and water to make 20 mL, and use this solution as the standard solution. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and calculate the ratios, QT and QS, of the peak area of dibekacin to that of the internal standard. Calculate the amount of dibekacin by the following equa-tion: not more than 2.0z. Amount (z) of dibekacin ＝ MS/MT × QT/QS × 1/10 × 100 MS: Amount [mg (potency)] of Dibekacin Sulfate RS taken MT: Amount (mg) of Arbekacin Sulfate taken Internal standard solution—A solution of bekanamycin sul-fate (1 in 2000). Operating conditions— Detector: Fluorometric detector (excitation wavelength: 340 nm, detection wavelength: 460 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Reaction coil: A column about 0.3 mm in inside diameter and about 3 m in length. Reaction coil temperature: A constant temperature of about 509C. Mobile phase: Dissolve 8.70 g of sodium 1-pentane sul-fonate and 8.52 g of anhydrous sodium su…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform the test according to the Cylinder-plate method as directed under Microbial Assay for Antibiotics <4.02> according to the following conditions. Test organism—Bacillus subtilis ATCC 6633 Culture medium—Use the medium i in 1) under (1) Agar media for seed and base layer, having pH 7.8 – 8.0 after sterilization. Standard solutions—Weigh accurately an amount of Arbekacin Sulfate RS, previously dried, equivalent to about 20 mg (potency), dissolve in diluted phosphate buffer solu-tion (pH 6.0) (1 in 2) to make exactly 50 mL, and use this so-lution as the standard stock solution. Keep the standard stock solution at 5 to 159C and use within 30 days. Take ex-actly a suitable amount of the standard stock solution before use, add 0.1 mol/L phosphate buffer solution (pH 8.0) to make solutions so that each mL contains 20 mg (potency) and 5 mg (potency), and use these solutions as the high concentra-tion standard solution and low concentration standard solu-tion, respectively. Sample solutions—Weigh accurately an amount of Arbekacin Sulfate, equivalent to about 20 mg (potency), and dissolve in water to make exactly 50 mL. Take exactly a suitable amount of this solution, add 0.1 mol/L phosphate buffer solution (pH 8.0) to make solutions so that each mL contains 20 mg (potency) and 5 mg (potency), and use these solutions as the high concentration sample solution and low concentration sample solution, respectively.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

argatroban-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Argatroban Hydrate
  ja: アルガトロバン水和物
monograph id: JP18-argatroban-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C23H36N6O5S.H2O
molecular weight: 526.65
cas number: 141396-28-3
appearance:
  en: Argatroban Hydrate occurs as white, crystals or crystalline powder. It has a bitter taste. It is freely soluble in acetic acid (100), sparingly soluble in methanol, slightly soluble in ethanol (99.5), and very slightly soluble in water. It is gradually decomposed on exposure to light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Argatroban Hydrate in ethanol (99.5) (1 in 20,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Ar-gatroban Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋175 – ＋1859(0.2 g calcu-lated on the anhydrous basis, methanol, 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Argatroban Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Incinerate 2.0 g of Argatroban Hy- drate according to Method 4. After cooling, add 10 mL of dilute hydrochloric acid to the residue, dissolve by warming on a water bath, and perform the test using this solution as the test solution. Add 10 mL of a solution of magnesium ni-trate hexahydrate in ethanol (95) (1 in 10), then add 1.5 mL of hydrogen peroxide (30), and fire to burn (not more than 1 ppm). Related substance 1—Dissolve 50 mg of Argatroban Hydrate in 40 mL of methanol, add water to make 100 mL, and use this solution as the sample solution. Perform the test with 10 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the following condi-tions. Determine each peak area from the sample solution by the automatic integration method, and calculate the amount of them by the area percentage method: the amount of each peak other than argatroban is not more than 0.1z. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 459C. Mobile phase A: To 2.5 mL of acetic acid (100) add water to make 1000 mL, and adjust the pH to 5.0 with ammonia TS. To 500 mL of this solution add 500 mL of methanol. Mobile phase B: To 2.5 mL of acetic acid (100) add water to make 1000 mL, and adjust the pH to 5.0 with ammonia TS. To 200 mL of this solution add 800 mL of methanol. Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. the procedure is run with 10 mL of this solution under the above operating conditions, methyl…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Argatroban Hy-drate, dissolve in 20 mL of acetic acid for nonaqueous titra-tion, add 40 mL of acetone for nonaqueous titration, and ‌JP XVIII Official Monographs / L-Arginine Hydrochloride 481‌ titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 50.86 mg of C23H36N6O5S
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

aromatic-castor-oil
type: ChemicalDrugMonograph
pref label:
  en: Aromatic Castor Oil
  ja: 加香ヒマシ油
monograph id: JP18-aromatic-castor-oil
publisher: JP
status: Official
version: 18
appearance:
  en: Aromatic Castor Oil is a colorless or yellow-ish, clear, viscous liquid. It has an aromatic odor.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 3 g of Aromatic Castor Oil add 1 g of po-tassium hydroxide, and heat the mixture carefully to fuse: a characteristic odor is perceptible. Dissolve the fused matter in 30 mL of water, add an excess of magnesium oxide, and filter. Acidify the filtrate with hydrochloric acid: white crys-tals are produced.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

arotinolol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Arotinolol Hydrochloride
  ja: アロチノロール塩酸塩
monograph id: JP18-arotinolol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C15H21N3O2S3.HCl
molecular weight: 408.0
cas number: 68377-91-3
definition:
  en: Arotinolol Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Arotinolol Hydrochloride occurs as a white to light yellow crystalline powder. It is freely soluble in dimethylsulfoxide, slightly soluble in methanol and in water, very slightly soluble in ethanol (99.5), and practically insoluble in diethyl ether. ‌JP XVIII Official Monographs / Arsenical Paste 483 A solution of Arotinolol Hydrochloride in methanol (1 in 125) does not show optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Arotinolol Hydrochloride in methanol (1 in 75,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Arotinolol Hydrochloride, previously dried, as directed in the potassium bromide disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Arotinolol Hydrochloride (1 in 200) responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Arotinolol Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 0.05 g of Arotinolol Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 100 mL. Pipet 1 mL of this solution, add methanol to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 40 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform, methanol, acetone and ammonia solution (28) (30:10:10:1) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.20z (1 g, in vacu-um, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 1.5 g of Arotinolol Hydro-chloride, previously dried, dissolve in dimethylsulfoxide to make exactly 25 mL. Pipet 5 mL of this solution, add 100 mL of water and 5 mL of sodium hydroxide TS, and extract with three 50-mL portions of dichloromethane. Filter each dichloromethane extract through a pledget of absorbent cot-ton with anhydrous sodium sulfate on it. Evaporate com-bined filtrate to dryness in vacuum. Dissolve the residue in 70 mL of acetic acid (100), and titrate <2.50> with 0.05 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.05 mol/L perchloric acid VS ＝ 20.40 mg of C15H21N3O2S3.HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

arsenic-trioxide
type: ChemicalDrugMonograph
pref label:
  en: Arsenic Trioxide
  ja: 三酸化二ヒ素
monograph id: JP18-arsenic-trioxide
publisher: JP
status: Official
version: 18
molecular formula: As2O3
molecular weight: 197.84
definition:
  en: Arsenic Trioxide, when dried, contains not less than 99.
appearance:
  en: Arsenic Trioxide occurs as a white powder. It is odorless. It is practically insoluble in water, in ethanol (95) and in diethyl ether. It dissolves in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Dissolve 0.2 g of Arsenic Trioxide in 40 mL of water by heating on a water bath: the solution responds to Qualitative Tests <1.09> for arsenite.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Clarity of solution—To 1.0 g of Arsenic Trioxide add 10 mL of ammonia TS, and heat gently: the solution is clear. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of Arsenic Trioxide, previously dried, dissolve in 20 mL of a solution of sodium hydroxide (1 in 25), by warming, if necessary. Add 40 mL of water and 2 drops of methyl orange TS, then add dilute hydrochloric acid until the color of the solution becomes light red. Add 2 g of sodium hydrogen carbonate and 50 mL of water to this solution, and titrate <2.50> with 0.05 mol/L iodine VS (indicator: 3 mL of starch TS). Each mL of 0.05 mol/L iodine VS ＝ 4.946 mg of As2O3
storage conditions:
  en: Containers—Tight containers.

arsenical-paste
type: ChemicalDrugMonograph
pref label:
  en: Arsenical Paste
  ja: 亜ヒ酸パスタ
monograph id: JP18-arsenical-paste
publisher: JP
status: Official
version: 18
definition:
  en: Arsenical Paste contains not less than 36.
appearance:
  en: Arsenical Paste is grayish black and has the odor of clove oil.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Place 0.1 g of Arsenical Paste in a small flask, add 5 mL of fuming nitric acid and 5 mL of sulfuric acid, and heat over a flame until the reacting liquid becomes colorless and white fumes begin to evolve. After cooling, add the reacting liquid to 20 mL of water cautiously, and add 10 mL of hydrogen sulfide TS while warming: a yellow precipitate is produced (arsenic trioxide). Shake thoroughly 0.5 g of Arsenical Paste with 25 mL of diethyl ether, 5 mL of dilute hydrochloric acid and 20 mL of water, separate the water layer, and filter: 5 mL of the filtrate responds to Qualitative Tests <1.09> for primary aro-matic amines (procaine hydrochloride). Shake thoroughly 0.5 g of Arsenical Paste with 25 mL of diethyl ether and 25 mL of water, separate the water layer, filter, and use the filtrate as the sample solution. Dis-solve 0.01 g of procaine hydrochloride in 5 mL of water, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chroma-tography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent in-dicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, ethanol (99.5) and ammonia solution (28) (50:5:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wave-length: 254 mm): the spots obtained from the sample solu-tion and standard solution exhibit the same Rf value.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Arsenical Paste into a 150-mL Kjeldahl flask, add 5 mL of fuming nitric acid and 10 mL of sulfuric acid, and shake thoroughly. Heat cau-tiously the mixture, gently at first, and then continue strong heating, until red fumes of nitrogen oxide are sparingly evolved. After cooling, add 5 mL of fuming nitric acid, heat again until red fumes of nitrogen oxide are no longer evolved and the reacting liquid becomes clear, and cool. Add 30 mL of a saturated solution of ammonium oxalate monohydrate, heat again until white fumes of sulfuric acid are evolved, and continue the heating for 10 minutes. Decompose completely oxalic acid, cool, transfer cautiously the colorless reacting liquid to a glass-stoppered flask, containing 40 mL of water. Wash thoroughly the Kjeldahl flask with 60 mL of water, add the washings to the content of the glass-stoppered flask, and cool. Dissolve 3 g of potassium iodide in this solution, ‌484‌‌ allow to stand in a dark place at room temperature for 45 minutes, and titrate <2.50> the liberated iodine with 0.1 mol/L sodium thiosulfate VS (indicator: 5 mL of starch TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium thiosulfate VS ＝ 4.946 mg of As2O3
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

aspoxicillin-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Aspoxicillin Hydrate
  ja: アスポキシシリン水和物
monograph id: JP18-aspoxicillin-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C21H27N5O7S.3H2O
molecular weight: 547.58
definition:
  en: Aspoxicillin Hydrate contains not less than 950 mg (potency) and not more than 1020 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Aspoxicillin Hydrate occurs as a white, crys-tals or crystalline powder. It is freely soluble in N,N-dimethylformamide, sparingly soluble in water, and practically insoluble in acetonitrile, in methanol and in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Aspoxicillin Hydrate (1 in 4000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Aspoxicillin RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. pH <2.54> Dissolve 1.0 g of Aspoxicillin Hydrate in 50 mL of water: the pH of the solution is between 4.2 and 5.2.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Aspoxicillin Hydrate in 50 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g of Aspoxi- cillin Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 2.0 g of Aspoxicillin Hydrate according to Method 5, and perform the test (not more than 1 ppm). Related substances—Dissolve 0.05 g of Aspoxicillin Hydrate in 10 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of these solutions as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the areas of each peak by the au-tomatic integration method: the area of each peak other than aspoxicillin obtained from the sample solution is not larger than 3/10 times the peak area of aspoxicillin from the stand-ard solution, and the total of peak areas other than aspox-icillin from the sample solution is not larger than the peak area of aspoxicillin from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 6 times as long as the retention time of aspoxicillin. System suitability— System performance: Proceed as directed in the system suitability in the Assay. Test for required detectability: Pipet 2 mL of the standard solution, add the mobile phase to make exactly 10 mL. Con-firm that the peak area of aspoxicillin obtained with 10 mL of this solution is equivalent to 15 to 25z of that with 10 mL of the standard solution. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Aspoxicillin Hy-drate and Aspoxicillin RS, equivalent to about 0.1 g (po-tency), dissolve each in a suitable amount of water, add exactly 10 mL of the internal standard solution, 6.5 mL of acetonitrile and water to make 50 mL, and use these solu-tions as the sample solution and the standard solution, respectively. Perform the test with 10 mL each of these solu-tions as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and calculate the ratios, QT and QS, of the peak area of aspoxicillin to that of the in- ‌JP XVIII Official Monographs / Atenolol 491 ternal standard. Amount [ mg (potency)] of aspoxicillin (C21H27N5O7S) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Aspoxicillin RS taken Internal standard solution—A solution of N-(3-hydroxy-phenyl)acetamide (1 in 1000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: To 130 mL of acetonitrile add potassium dihydrogenphosphate TS (pH 3.0) to make 1000 mL. Flow rate: Adjust so that the retention time of aspoxicillin is about 3 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, aspoxicillin and the internal standard are eluted in this order with the resolution between these peaks being not less than 8. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of aspoxicillin to that of the internal stand-ard is not more than 0.8z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

atenolol
type: ChemicalDrugMonograph
pref label:
  en: Atenolol
  ja: アテノロール
monograph id: JP18-atenolol
publisher: JP
status: Official
version: 18
molecular formula: C14H22N2O3
molecular weight: 266.34
definition:
  en: Atenolol, when dried, contains not less than 99.
appearance:
  en: Atenolol occurs as a white to pale yellow crys-talline powder. It is freely soluble in methanol and in acetic acid (100), soluble in ethanol (99.5), and slightly soluble in water. A solution of Atenolol in methanol (1 in 25) shows no op-tical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Atenolol in methanol (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Atenolol as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Melting Pint <2.60> 152 – 1569C
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Atenolol according to Method 2, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 20 ppm). (2) Related substances—Dissolve 50 mg of Atenolol in 25 mL of the mobile phase, and use this solution as the sam-ple solution. Pipet 1 mL of the sample solution, add the mo-bile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine each peak area by the automatic integration method: the area of the peak other than atenolol obtained from the sample solution is not larger than 1/2 times the peak area of atenolol from the standard solution, and the total area of the peaks other than atenolol from the sample solution is not larger than the peak area of atenolol from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 226 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 3.4 g of potassium dihydrogen phosphate in 1000 mL of water, and adjust to pH 3.0 with phosphoric acid. To 40 volume of this solution add 9 volume of methanol and 1 volume of tetrahydrofuran. Dissolve 1 g of sodium 1-octanesulfonate and 0.4 g of tetrabutylammo-nium hydrogensulfate in 1000 mL of this solution. Flow rate: Adjust so that the retention time of atenolol is about 8 minutes. Time span of measurement: About 4 times as long as the retention time of atenolol. System suitability— Test for required detectability: To exactly 10 mL of the standard solution add the mobile phase to make exactly 50 mL. Confirm that the peak area of atenolol obta…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Atenolol, previ-ously dried, dissolve in 100 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 26.63 mg of C14H22N2O3
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

atropine-sulfate-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Atropine Sulfate Hydrate
  ja: アトロピン硫酸塩水和物
monograph id: JP18-atropine-sulfate-hydrate
publisher: JP
status: Official
version: 18
molecular formula: NO3)2.H2SO4.H2O
molecular weight: 694.83
cas number: 5908-99-6
definition:
  en: Atropine Sulfate Hydrate, when dried, contains not rately about 44 mg of Atorvastatin Calcium RS (separately determine the water <2.
appearance:
  en: Atropine Sulfate Hydrate occurs as colorless crystals or a white crystalline powder. It is odorless. It is very soluble in water and in acetic acid (100), freely soluble in ethanol (95), and practically insoluble in diethyl ether. Melting point: 188 – 1949C (with decomposition). Intro-duce a capillary tube charged with dried sample into a bath previously heated to 1809C, and continue to heat at a rate of rise of about 39C per minute. It is affected by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mg of Atropine Sulfate Hydrate add 3 drops of fuming nitric acid, and evaporate the mixture on a water bath to dryness. Dissolve the residue in 1 mL of N,N-dimethylformamide, and add 5 to 6 drops of tetraethyl-ammonium hydroxide TS: a red-purple color develops. To 2 mL of a solution of Atropine Sulfate Hydrate (1 in 50) add 4 to 5 drops of hydrogen tetrachloroaurate (III) TS: a lusterless, yellow-white precipitate is formed. To 5 mL of a solution of Atropine Sulfate Hydrate (1 in 25) add 2 mL of ammonia TS, and allow to stand for 2 to 3 minutes. Collect the precipitate, wash with water, and dry in a desiccator (in vacuum, silica gel) for 4 hours: it melts <2.60> between 1159C and 1189C. A solution of Atropine Sulfate Hydrate (1 in 20) re-sponds to Qualitative Tests <1.09> for sulfate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution —Dissolve 0.5 g JP XVIII Official Monographs / Atropine Sulfate Injection 495 of Atropine Sulfate Hydrate in 10 mL of water: the solution is clear and colorless. ‌Acidity—Dissolve 1.0 g of Atropine Sulfate Hydrate in 20 mL of water, and add 0.30 mL of 0.02 mol/L sodium hydroxide VS and 1 drop of methyl red-methylene blue TS: a green color develops. Related substances—Dissolve 0.25 g of Atropine Sul-fate Hydrate in 1 mL of diluted hydrochloric acid (1 in 10), add water to make 15 mL, and use this solution as the sam-ple solution. To 5 mL of the sample solution add 2 to 3 drops of hydrogen hexachloroplatinate (IV) TS: no precipitate is formed. To 5 mL of the sample solution add 2 mL of ammo-nia TS, and shake vigorously: the turbidity of the solution is not greater than that of the following control solution. Control solution: To 0.30 mL of 0.01 mol/L hydrochloric acid VS add 6 mL of dilute nitric acid and water to make 50 mL. To this solution add 1 mL of silver nitrate TS, and allow 7 mL of the mixture to stand for 5 minutes. D Hyoscyamine—Weigh accurately about 1 g of Atro-pine Sulfate Hydrate, previously dried, and dissolve in water to make exactly 10 mL: the specific optical rotation [a]20 <2.49> of this solution in a 100-mm cell is between －0.609 and ＋0.109. Readily carbonizable substances <1.15>—Take 0.20 g of Atropine Sulfate Hydrate, and perform the test: the solu-tion has no more color than Matching Fluid A. Loss on drying <2.41> Not more than 4.0z (0.5 g, in vacu-um, phosphorus (V) oxide, 1109C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (0.5 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Dissolve about 0.25 g of Atropine Sulfate Hydrate, previously dried and accurately weighed, in 30 mL of acetic acid (100). If necessary, dissolve it by warming, and cool. Titrate <2.50> with 0.05 mol/L perchloric acid VS until the color of the solution changes from purple through blue to blue-green (indicator: 3 drops of crystal violet TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.05 mol/L perchloric acid VS ＝ 33.84 mg of (C17H23NO3)2.H2SO4
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

auranofin
type: ChemicalDrugMonograph
pref label:
  en: Auranofin
  ja: オーラノフィン
monograph id: JP18-auranofin
publisher: JP
status: Official
version: 18
molecular formula: C20H34AuO9PS
molecular weight: 678.48
definition:
  en: Auranofin, when dried, contains not less than 98.
appearance:
  en: Auranofin occurs as a white crystalline pow-der. It is very soluble in chloroform, freely soluble in metha-nol, sparingly soluble in ethanol (99.5), and practically in-soluble in water. It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 50 mg of Auranofin add 3 mL of water, 3 mL of nitric acid and 3 mL of sulfuric acid, shake, and allow to stand: golden colored suspended matters are produced. Determine the infrared absorption spectrum of Auranofin as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Auranofin RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Prepare the test solution with 1 mg of Auranofin as directed under Oxygen Flask Combustion Method <1.06>, using 10 mL of water as the absorbing liquid. Wash out the test solution into a Nessler tube with water to make 30 mL. Add 10 mL of dilute sulfuric acid, 3 mL of hexaammonium heptamolybdate-sulfuric acid TS and 0.1 mL of tin (II) chlo-ride TS, shake, and allow to stand for 10 to 15 minutes: a blue color is developed. D Optical rotation <2.49> [a]20: －54.0 – －62.09(after dry-ing, 0.2 g, methanol, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Put 0.5 g of Auranofin in a porcelain crucible, add 0.25 g of anhydrous sodium carbon-ate, mix well, and ignite until the carbonized substance is dis-appeared. After cooling, add 20 mL of water, heat, and filter after cooling. Wash the residue with 20 mL of water, combine the filtrate and the washings, neutralize with dilute nitric acid, then add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: Dissolve 0.25 g of anhydrous sodium carbonate in 20 mL of water, neutralize with dilute nitric acid, add 0.50 mL of 0.01 mol/L hydrochloric acid, 6 mL of dilute nitric acid, and water to make 50 mL (not more than 0.036z). Heavy metals <1.07>—Proceed with 1.0 g of Auranofin according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Put 0.5 g of Auranofin in a Kjeldahl flask, add cautiously 2 mL of sulfuric acid and 5 mL of nitric acid, and heat until the solution becomes almost color-less. After cooling, add 15 mL of a saturated solution of am-monium oxalate monohydrate, heat until white fumes are evolved, and concentrate to 1 to 2 mL. Then, add 3 mL of water and 1 drop of methyl orange TS, neutralize with am-monia solution (28), filter, and perform the test using the fil-trate as the test solution: the color is not darker than that of the following control solution. Control solution: Heat a mixture of 2 mL of sulfuric acid and 5 mL of nitric acid until white fumes are no longer evolved. After cooling, add 15 mL of a saturated solution of ammonium oxalate monohydrate, heat until white fumes are evolved, and concentrate to 1 to 2 mL. Add 3 mL of water and 1 drop of methyl orange TS, neutralize with ammonia solution (28), and filter. To the filtrate add 2.0 mL of Stand-ard Arsenic Solution, then proceed in the same manner as for the test solution (not more than 4 ppm)…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 20 mg each of Auranofin and Auranofin RS, both previously dried, dissolve each in 10 mL of a mixture of water and acetonitrile (1:1), and add exactly 5 mL each of the internal standard solution. Then add a mixture of water and acetonitrile (1:1) to make 100 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and calculate the ratios, QT and QS, of JP XVIII Official Monographs / Auranofin Tablets 497 ‌the peak area of auranofin to that of the internal standard. Amount (mg) of auranofin (C20H34AuO9PS) ＝ MS × QT/QS MS: Amount (mg) of Auranofin RS taken Internal standard solution—A solution of butyl para-hydroxybenzoate in a mixture of water and acetonitrile (1:1) (3 in 1250). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 230 nm). Column: A stainless steel column 4 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of sodium dihydrogen phosphate dihydrate solution (1 in 100), tetrahydrofuran and aceto-nitrile (12:5:3). Flow rate: Adjust so that the retention time of auranofin is about 6 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, auranofin and the internal standard are eluted in this order with the resolution between these peaks being not less than 9. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratio of the peak area of auranofin to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

aurantii-pericarpium
type: ChemicalDrugMonograph
pref label:
  en: Aurantii Pericarpium
  ja: トウヒ
monograph id: JP18-aurantii-pericarpium
publisher: JP
status: Official
version: 18
appearance:
  en: Usually quartered sections of a sphere, some-times warped or flattened, 4 – 8 cm in length, 2.5 – 4.5 cm in width and 0.5 – 0.8 cm in thickness; the outer surface is dark red-brown to grayish yellow-brown, with numerous small dents associated with oil sacs; the inner surface is white to light grayish yellow-red, with irregular indented reticulation left by vascular bundles; light and brittle in texture. Odor, characteristic aroma; taste, bitter, somewhat mucilaginous and slightly pungent.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 1.0 g of Bitter Orange Peel add 10 mL of ethanol (95), allow to stand for 30 minutes with occasional shaking, filter, and use the filtrate as the sample solution. Separately, dissolve 10 mg of naringin for thin-layer chroma-tography in 10 mL of ethanol (95), and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, ethanol (99.5) and water (8:2:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly dilute 2,6-dibromo-N-chloro-1,4-benzo-quinone monoimine TS on the plate, and allow to stand in ammonia gas: one of the several spots obtained from the sample solution and a grayish green spot from the standard solution show the same color tone and the same Rf value. Loss on drying <5.01> Not more than 14.0z (6 hours). Total ash <5.01> Not more than 5.5z. Acid-insoluble ash <5.01> Not more than 0.5z. Essential oil content <5.01> Perform the test with 50.0 g of pulverized Bitter Orange Peel provided that 1 mL of silicon resin is previously added to the test sample in the flask: the volume of essential oil is not less than 0.2 mL.
storage conditions:
  en: Containers—Well-closed contain-ers.

azathioprine
type: ChemicalDrugMonograph
pref label:
  en: Azathioprine
  ja: アザチオプリン
monograph id: JP18-azathioprine
publisher: JP
status: Official
version: 18
molecular formula: C9H7N7O2S
molecular weight: 277.26
definition:
  en: Azathioprine, when dried, contains not less than 98.
appearance:
  en: Azathioprine is light yellow, crystals or crystal-line powder. It is odorless. It is sparingly soluble in N,N-dimethylformamide and in pyridine, very slightly soluble in water and in ethanol (99.5), and practically insoluble in chloroform and in diethyl ether. It dissolves in sodium hydroxide TS and in ammonia TS. It is gradually colored by light. Melting point: about 2409C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Azathioprine in 50 mL of water by warming. To 5 mL of this solution add 1 mL of dilute hydrochloric acid and 0.01 g of zinc powder, and allow to stand for 5 minutes: a yellow color is produced. Filter this solution: the filtrate responds to Qualitative Tests <1.09> for primary aromatic amines, and a red color is pro- duced. Dissolve 0.01 g of Azathioprine in 50 mL of water by warming. To 1 mL of this solution add 0.5 mL of phos-photungstic acid TS and 0.5 mL of dilute hydrochloric acid: a white precipitate is formed. Prepare the test solution by proceeding with 0.03 g of Azathioprine according to Oxygen Flask Combustion Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Azathioprine RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorp-tion at the same wavelengths.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Azathioprine in 50 mL of N,N-dimethylformamide: the solution is clear and shows a light yellow color. Acidity or alkalinity—Add 100 mL of water to 2.0 g of Azathioprine, shake well for 15 minutes, centrifuge for 5 minutes at 10,000 revolutions per minute, and filter. Discard the first 20 mL of the filtrate, add 2 drops of methyl red TS to 40 mL of the subsequent filtrate, and use this solution as the sample solution. Add 0.10 mL of 0.02 mol/L hydrochloric acid VS to 20 mL of the sample solution: a red color develops. Add 0.10 mL of 0.02 mol/L sodium hydroxide VS to 20 mL of the sample solution: a yellow color develops. Sulfate <1.14>—To 25 mL of the filtrate obtained in (2) add 1 mL of dilute hydrochloric acid and water to make 50 mL, and perform the test using this solution as the test so-lution. Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not more than 0.038z). Heavy metals <1.07>—Proceed with 2.0 g of Azathioprine according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Azathioprine, according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 10 mg of Azathioprine in 80 mL of the mobile phase by warming, cool, add the mobile phase to make 100 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method: the total area of the peaks other than azathioprine obtained from the sample solution is not larger than 1/2 times the peak area of azathioprine from the standard solution. Operatin…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Azathioprine, pre- as the sample solution. Separately, dissolve 0.1 g of Azathioprine RS in 10 mL of a solution of ammonia solution (28) in ethanol (95) (1 in 10), and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethanol (95), ethyl acetate, and ammonia solution (28) (5:5:1) to a distance of about 7 cm, and air-dry the plate. Ex-amine under ultraviolet light (main wavelength: 254 nm): the spots obtained from the sample solution and the standard solution show the same Rf value. Uniformity of dosage units <6.02> Perform the Mass varia-tion test, or the Content uniformity test according to the fol-lowing method: it meets the requirement. To 1 tablet of Azathioprine Tablets add 1 mL of dimethyl-sulfoxide for ultraviolet-visible spectrophotometry per 5 mg of azathioprine (C9H7N7O2S), shake well, add 0.1 mol/L hy-drochloric acid TS to make exactly V mL so that each mL contains about 0.2 mg of azathioprine (C9H7N7O2S), and filter. Discard the first 20 mL of the filtrate, pipet 3 mL of the subsequent filtrate, add 0.1 mol/L hydrochloric acid TS to make exactly 100 mL, and use this solution as the sample solution. Then, proceed as directed in the Assay. Amount (mg) of azathioprine (C H N O S) viously dried, add 80 mL of N,N-dimethylformamide, and warm to dissolve. After cooling, titrate <2.50> with 0.1 ＝ MS × AT/AS × V/500 9 7 7 2 mol/L tetramethylammonium hydroxide VS until the color of the solution changes from yellow through yellow-green to blue-green (indicator: 1 mL of thymol blue-dimethylfor-mamide TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L tetramethylammonium hydroxide VS ＝ 27.73 mg of C9H7O7O2S
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

azelastine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Azelastine Hydrochloride
  ja: アゼラスチン塩酸塩
monograph id: JP18-azelastine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C22H24ClN3O.HCl
molecular weight: 418.36
cas number: 79307-93-0
appearance:
  en: Azelastine Hydrochloride occurs as a white crystalline powder. It is freely soluble in formic acid, and slightly soluble in water and in ethanol (99.5). Melting point: about 2259C (with decomposition). A solution of Azelastine Hydrochloride (1 in 200) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Azelastine Hydrochloride (3 in 100,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Azelastine Hydrochloride as directed in the potassium chlo-ride disk method under Infrared Spectrophotometry <2.25>: both spectra exhibit similar intensities of absorption at the same wave numbers. To 10 mL of a saturated solution of Azelastine Hydrochloride add 1 mL of dilute nitric acid, and filter to separate formed crystals: the filtrate responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Azelastine Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). each peak area other than azelastine obtained from the sam-ple solution is not larger than 1/10 times the peak area of azelastine from the standard solution, and the total area of the peaks other than the peak of azelastine from the sample solution is not larger than 1/2 times the peak area of azelastine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 240 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 359C. Mobile phase: A mixture of water, acetonitrile and per-chloric acid (660:340:1). Flow rate: Adjust so that the retention time of azelastine is about 10 minutes. Time span of measurement: About 2 times as long as the retention time of azelastine, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 5 mL of the standard solution, and add the mobile phase to make exactly 50 mL. Confirm that the peak area of azelastine obtained with 20 mL of this solution is equivalent to 7 to 13z of that with 20 mL of the standard solution. System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of azelastine is not less than 5000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of azelastine is not more than 1.0z. Loss on drying <2.41> Not more than 1.0z (1 g, 1059C, 2 hours). Residue on ignition…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of previously dried Azelastine Hydrochloride, dissolve in 5 mL of formic acid, add 70 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 41.84 mg of C22H24ClN3O.HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

azelnidipine
type: ChemicalDrugMonograph
pref label:
  en: Azelnidipine
  ja: アゼルニジピン
monograph id: JP18-azelnidipine
publisher: JP
status: Official
version: 18
cas number: 123524-52-7
definition:
  en: Azelnidipine contains not less than 99.
appearance:
  en: Azelnidipine occurs as a light yellow to yellow, crystalline powder or powder containing masses. It is freely soluble in ethanol (99.5) and in acetic acid (100), and practically insoluble in water. A solution of Azelnidipine in ethanol (99.5) (1 in 100) shows no optical rotation. Azelnidipine shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Azelnidipine in ethanol (99.5) (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Azel-nidipine as directed in the paste method under Infrared Spec-trophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Azelnidipine according to Method 2, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 0.10 g of Azelnidipine in a mixture of acetonitrile and water (4:1) to make 100 mL, and use this solution as the sample solution. Pipet 2 mL of the sample solution, add a mixture of acetonitrile and water (4:1) to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method: the areas of the peak, having the relative retention time of about 0.50 and about 1.42 to azel-nidipine, obtained from the sample solution are not larger than 1/5 times and 3/10 times the peak area of azelnidipine from the standard solution, respectively, the area of the peak other than azelnidipine and the peaks mentioned above from the sample solution is not larger than 1/10 times the peak area of azelnidipine from the standard solution, and the total area of the peaks other than azelnidipine from the sam-ple solution is not larger than 7/10 times the peak area of azelnidipine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave- length: 220 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 1.05 g of potassium dihydrogen phosphate in 350 mL of water, add 650 mL of a mixture of acetonitrile and methanol (7:3), and adjust to pH 5.5 with diluted phosphoric acid (1 in 10). Flow rate: Adjust so that the retention time of azelnidi-pine is about 36 minutes. Time span of measuremen…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Azelnidipine, dis-solve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 29.13 mg of C33H34N4O6
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

azithromycin-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Azithromycin Hydrate
  ja: アジスロマイシン水和物
monograph id: JP18-azithromycin-hydrate
publisher: JP
status: Official
version: 18
cas number: 117772-70-0
appearance:
  en: Azithromycin Hydrate occurs as a white crys-talline powder. It is freely soluble in methanol and in ethanol (99.5), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Azithromycin Hydrate as directed in the potassium bro-mide disk method under the Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum or the spectrum of Azithromycin RS: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －45 – －499(0.4 g calculated on the anhydrous basis, ethanol (99.5), 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Azithromycin Hydrate according to Method 2, and perform the test. Prepare the control solution with 1.0 mL of Stand-ard Lead Solution (not more than 10 ppm). (2) Related substances—Being specified separately when the drug is granted approval based on the Law. Water <2.48> Not less than 4.0z and not more than 5.0z (0.4 g, volumetric titration, direct titration). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Azithromycin Hy-drate and Azithromycin RS, equivalent to about 50 mg (po-tency), dissolve each in an adequate amount of a mixture of acetonitrile and water (3:2), add exactly 2 mL of the internal standard solution and the mixture of acetonitrile and water (3:2) to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and calculate the ratios, QT and QS, of the peak area of azithromycin to that of the internal stand-ard. Amount [ mg (potency)] of azithromycin (C38H72N2O12) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Azithromycin RS taken Internal standard solution—A solution of 4,4?-bis(diethylamino)benzophenone in acetonitrile (3 in 4000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 215 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized poly-vinyl alcohol gel polymer for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 6.97 g of dipotassium hydrogen phosphate in about 750 mL of water, adjust the pH to 11.0 with potassium hydroxide TS, and add water to make 1000 mL. To 400 mL of this solution add 600 mL of acetonitrile for liquid chromatography. Flow rate: Adjust so that the retention time of azithromy-cin is about 10 minutes. System suitability— System performance: When the procedure is run with 5 mL of the standard solution under the above operating condi-tions, azithromycin and the internal standard are eluted in this order with the resolution between these peaks being not less than 2.0. System repeatability: When the test is repeated 6 times with 5 mL of the standard solution under the above operating conditions, the relative standard deviation of the rati…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

azosemide
type: ChemicalDrugMonograph
pref label:
  en: Azosemide
  ja: アゾセミド
monograph id: JP18-azosemide
publisher: JP
status: Official
version: 18
cas number: 27589-33-9
definition:
  en: Azosemide, when dried, contains not less than 99.
appearance:
  en: Azosemide occurs as a white to yellow-white crystalline powder. It is freely soluble in N,N-dimethylformamide, slightly soluble in methanol and in ethanol (99.5), and practically in-soluble in water. It dissolves in dilute sodium hydroxide TS. It is gradually colored to yellow by light. Each mL of 0.1 mol/L potassium hydroxide-ethanol VS ＝ 37.08 mg of C12H11ClN6O2S2
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Azosemide, previ-ously dried, dissolve in 50 mL of N,N-dimethylformamide, and titrate <2.50> with 0.1 mol/L potassium hydroxide-ethanol VS until the color of the solution changes from yel-low to yellow-green (indicator: 10 drops of thymol blue-N,N-dimethylformamide TS). Perform a blank determina-tion in the same manner with a solution prepared by adding 15 mL of ethanol (95) to 50 mL of N,N-dimethylformamide, 12 11 6 2 2 and make any necessary correction. 2-Chloro-5-(1H-tetrazol-5-yl)-4-[(thien-2-ylmethyl)amino] benzenesulfonamide [27589-33-9] Azosemide, when dried, contains not less than 99.0z and not more than 101.0z of azosemide (C12H11ClN6O2S2). Description Azosemide occurs as a white to yellow-white crystalline powder. It is freely soluble in N,N-dimethylformamide, slightly soluble in methanol and in ethanol (99.5), and practically in-soluble in water. It dissolves in dilute sodium hydroxide TS. It is gradually colored to yellow by light. Each mL of 0.1 mol/L potassium hydroxide-ethanol VS ＝ 37.08 mg of C12H11ClN6O2S2
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

aztreonam
type: ChemicalDrugMonograph
pref label:
  en: Aztreonam
  ja: アズトレオナム
monograph id: JP18-aztreonam
publisher: JP
status: Official
version: 18
molecular formula: C13H17N5O8S2
molecular weight: 435.43
cas number: 78110-38-0
definition:
  en: Aztreonam contains not less than 920 mg (potency) and not more than 1030 mg (potency) per mg, calcu-lated on the anhydrous basis.
appearance:
  en: Aztreonam occurs as a white to yellowish white crystalline powder. It is freely soluble in dimethylsulfoxide, slightly soluble in water and in methanol, and very slightly soluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Aztreonam (3 in 100,000) as directed under Ul-traviolet-visible Spectrophotometry <2.24>, and compare the JP XVIII Official Monographs / Aztreonam for Injection 507 spectrum with the Reference Spectrum or the spectrum of a solution of Aztreonam RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the spectrum of a solution of Aztreonam in deuterated dimethylsulfoxide for nuclear magnetic reso-nance spectroscopy (1 in 10), using a light hydrogen sub-stance existing in deuterated dimethylsulfoxide for nuclear magnetic resonance spectroscopy as an internal reference compound and 2.50 ppm for its chemical shift, as directed under Nuclear Magnetic Resonance Spectroscopy <2.21> (1H): it exhibits a multiple signal at around d 1.5 ppm, and a single signal at around d 7.0 ppm. The ratio of integrated in-tensity of each signal is 9:1. D Optical rotation <2.49> [a]20: －26 – －329(0.25 g calcu-lated on the anhydrous bases, water, 50 mL, 100 mm). pH <2.54> Dissolve 0.05 g of Aztreonam in 10 mL of water: the pH of this solution is between 2.2 and 2.8. ‌Purity (1) Clarity and color of solution—Dissolve 1.0 g of Aztreonam in 20 mL of dimethylsulfoxide: the solution is clear, and its absorbance at 420 nm, determined as directed under Ultraviolet-visible Spectrophotometry <2.24>, is not more than 0.06. Heavy metals <1.07>—Proceed with 2.0 g of Aztreo- nam according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 40 mg of Aztreonam in 100 mL of water, and use this solution as the sample solu-tion. Pipet 2 mL of the sample solution, add water to make exactly 100 mL, and use this solution as the standard solu-tion. Perform the test with exactly 25 mL each of the sample solution and standard solution as directed under Liquid Chromatogra…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Aztreonam and Az-treonam RS, equivalent to about 20 mg (potency), dissolve each in 70 mL of water, add exactly 10 mL of the internal standard solution and water to make 100 mL, and use these solutions as the sample solution and standard solution, re-spectively. Perform the test with 25 mL each of these solu-tions as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and calculate the ratios, QT and QS, of the peak area of aztreonam to that of the in-ternal standard. Amount [ mg (potency)] of aztreonam (C13H17N5O8S2) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Aztreonam RS taken Internal standard solution—A solution of 4-aminobenzoic acid (1 in 6250). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 1.7 g of tetrabutylammonium hydrogensulfate in 300 mL of water, adjust to pH 3.0 with 0.5 mol/L disodium hydrogenphosphate TS, and add water to make 1000 mL. To 650 mL of this solution add 350 mL of methanol. Flow rate: Adjust so that the retention time of aztreonam is about 8 minutes. System suitability— System performance: When the procedure is run with 25 mL of the standard solution under the above operating con-ditions, the internal standard and aztreonam are eluted in this order with the resolution between these peaks being not less than 4. System repeatability: When the test is repeated 6 times with 25 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of aztreonam to that of the internal stand-ard is not more than 1.5z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

b-galactosidase-aspergillus
type: ChemicalDrugMonograph
pref label:
  en: b-Galactosidase (Aspergillus)
  ja: b-ガラクトシダーゼ（アスペルギルス）
monograph id: JP18-b-galactosidase-aspergillus
publisher: JP
status: Official
version: 18
cas number: 9031-11-2
definition:
  en: b-Galactosidase (Aspergillus) contains an enzyme produced by Aspergillus oryzae.
appearance:
  en: b-Galactosidase (Aspergillus) occurs as a white to light yellow powder. It is slightly soluble in water with a turbidity, and practi-cally insoluble in ethanol (95) and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 25 mg of b-Galactosidase (Aspergillus) in 100 mL of water, then to 1 mL of this solu-tion add 9 mL of lactose substrate TS, and stand at 309C for 10 minutes. To 1 mL of this solution add 6 mL of glucose detection TS, and stand at 309C for 10 minutes: a red to red-purple color develops. (2) Dissolve 0.1 g of b-Galactosidase (Asperigillus) in 100 mL of water, and filter the solution if necessary. Deter-mine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Odor—b-Galactosidase (Aspergillus) has no ‌1054 any rancid odor. Heavy metals <1.07>—Proceed with 1.0 g of b-Galac-tosidase (Aspergillus) according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of b-Galactosidase (Aspergillus) according to Method 3, and perform the test (not more than 2 ppm). Loss on drying <2.41> Not more than 9.0z (0.5 g, in vacu-um, 809C, 4 hours). Residue on ignition <2.44> Not more than 3z (0.5 g). Nitrogen content Weigh accurately about 70 mg of b-Galactosidase (Aspergillus), and perform the test as directed under Nitrogen Determination <1.08>: the amount of nitro-gen (N: 14.01) is between 0.5z and 5.0z, calculated on the dried basis.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (i) Substrate solution—Dissolve 0.172 g of 2-nitrophenyl-b-D-galactopyranoside in disodium hydrogen-phosphate-citric acid buffer solution (pH 4.5) to make 100 mL. (ii) Procedure—Weigh accurately about 25 mg of b-Galactosidase (Aspergillus), dissolve in water to make ex-actly 100 mL, then pipet 2 mL of this solution, add water to make exactly 50 mL, and use this solution as the sample so-lution. Take exactly 3.5 mL of the substrate solution, stand at 30 ± 0.19C for 5 minutes, add exactly 0.5 mL of the sam-ple solution, immediately mix, and stand at 30 ± 0.19C for exactly 10 minutes, then add exactly 1 mL of sodium carbon-ate TS and mix immediately. Perfoum the test as directed under Ultraviolet-visible Spectrophotometry <2.24>, and de-termine the absorbance, A1, of this solution at 420 nm using water as the control. Separately, take exactly 3.5 mL of the substrate solution, add exactly 1 mL of sodium carbonate TS and mix, then add exactly 0.5 mL of the sample solution and mix. Determine the absorbance, A2, of this solution in the same manner as above. Units per g of b-Galactosidase (Aspergillus) ＝ 1/M × (A1 － A2)/0.917 × 1/0.5 × 1/10 0.917: Absorbance of 1 mmol/5 mL of o-nitrophenol M: Amount (g) of b-Galactosidase (Aspergillus) in the sample solution per mL Unit: One unit indicates an amount of the enzyme which decomposes 1 mmol of 2-nitrophenyl-b-D-galac-topyranoside in 1 minute under the above condi-tions.
storage conditions:
  en: Containers—Tight containers. Storage—In a cold place.

b-galactosidase-penicillium
type: ChemicalDrugMonograph
pref label:
  en: b-Galactosidase (Penicillium)
  ja: b-ガラクトシダーゼ（ペニシリウム）
monograph id: JP18-b-galactosidase-penicillium
publisher: JP
status: Official
version: 18
cas number: 9031-11-2
definition:
  en: b-Galactosidase (Penicillium) contains an enzyme, having lactose decomposition activity, produced by Penicillium multicolor.
appearance:
  en: b-Galactosidase (Penicillium) occurs as a white to pale yellow-white, crystalline powder or powder. It is soluble in water with a turbidity, and practically in-soluble in ethanol (95). It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.05 g of b-Galactosidase (Penicillium) in 100 mL of water, then to 0.2 mL of this so-lution add 0.2 mL of lactose substrate TS for b-galactosidase (penicillium), and allow to stand at 309C for 10 minutes. To this solution add 3 mL of glucose detection TS for penicilli-um origin b-galactosidase, and allow to stand at 309C for 10 minutes: a red to red-purple color develops. (2) Dissolve 0.15 g of b-Galactosidase (Penicillium) in 100 mL of water, filter if necessary, and determine the ab-sorption spectrum of this solution as directed under Ultravi-olet-visible Spectrophotometry <2.24>: it exhibits a maxi-mum between 278 nm and 282 nm.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Odor—b-Galactosidase (Penicillium) has no any rancid odor. Heavy metals <1.07>—Proceed with 1.0 g of b-Galac- tosidase (Penicillium) according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of b-Galactosidase (Penicillium) according to Method 3, and perform the test (not more than 2 ppm). Nitrogen—Weigh accurately about 0.1 g of b-Galac-tosidase (Penicillium), and perform the test as directed under Nitrogen Determination <1.08>: not more than 3 mg of nitro-gen (N: 14.01) is found for each labeled 1000 Units. Protein contaminants—Dissolve 0.15 g of b-Galac-tosidase (Penicillium) in 4 mL of water, and use this solution as the sample solution. Perform the test with 15 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the total area of the peaks other than the peak having retention time of about 19 minutes is not more than 75z of the total area of all peaks, and the areas of peaks other than the peaks having retention times of about 3, 16 and 19 minutes are not more than 15z of the total area of all peaks. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column about 7.5 mm in inside diameter and about 75 mm in length, packed with strongly acidic ion-exchange resin for liquid chromatography of sul-fopropyl group-binding hydrophilic polymer (10 mm in parti-cle diameter). Column temperature: A constant temperature of about 209C. Mobile phase: A solution obtained by dissolving 2.83 g of sodium acetate in 1000 mL of water, and adjusting to pH 4.5 with acetic acid (100) (mobile phase A), and a solution ob-tained by dissolving 29.2 g of sodium chloride in 1000 mL of mobile phase A (mobile phase B). Flow system: Adjust a linear concentration gradient…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (i) Substrate solution—Dissolve 0.603 g of 2-nitrophenyl-b-D-galactopyranoside in disodium hydrogen phosphate-citric acid buffer solution for penicillium origin b-galactosidase (pH 4.5) to make 100 mL. (ii) Procedure—Weigh accurately about 0.15 g of b-Galactosidase (Penicillium), dissolve in water with thorough shaking to make exactly 100 mL, and allow to stand at room temperature for an hour. Pipet 2 mL of this solution, add disodium hydrogen phosphate-citric acid buffer solution for penicillium origin b-galactosidase (pH 4.5) to make exactly 100 mL, and use this solution as the sample solution. Trans-fer exactly 0.5 mL of the sample solution to a test tube, stand at 30 ± 0.19C for 10 minutes, add exactly 0.5 mL of the substrate solution previously kept at 30 ± 0.19C, then mix immediately, and stand at 30 ± 0.19C for exactly 10 minutes. Then add exactly 1 mL of sodium carbonate TS, mix immediately to stop the reaction. To this solution add exactly 8 mL of water, mix, and use as the colored sample solution. Separately, pipet 0.5 mL of disodium hydrogen phosphate-citric acid buffer solution for penicillium origin b-galactosidase (pH 4.5), then proceed in the same manner as the sample solution, and use the solution so obtained as the colored blank solution. Perform the test with the colored sample solution and the colored blank solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, using water as the blank, and determine the absorbances, AT and AB, at 420 nm. Units per g of b-Galactosidase (Penicillium) ＝ 1/M × (AT － AB)/0.459 × 1/10 0.459: Absorbance of 1 mmol/10 mL of o-nitrophenol M: Amount (g) of b-Galactosidase (Penicillium) in 0.5 mL of the sample solution Unit: One unit indicates an amount of the enzyme which decomposes 1 mmol of 2-nitrophenyl-b-D-galac-topyranoside in 1 minute under the above condi-tions.
storage conditions:
  en: Containers—Tight containers.

bacampicillin-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Bacampicillin Hydrochloride
  ja: バカンピシリン塩酸塩
monograph id: JP18-bacampicillin-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C21H27N3O7S.HCl
molecular weight: 501.98
definition:
  en: Bacampicillin Hydrochloride is a hydrochloride of ampicillin ethoxycarbonyloxyethyl ester. It contains not less than 626 mg (potency) and not more than 710 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Bacampicillin Hydrochloride occurs as a white to pale yellow crystalline powder. It is freely soluble in methanol and in ethanol (95), and soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bacampicillin Hydrochloride in methanol (1 in 1000) as directed under Ultraviolet-visible Spectrophotome-try <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Bacampicillin Hy-drochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorp-tion at the same wavelengths. Determine the infrared absorption spectrum of Bacampicillin Hydrochloride as directed in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum or the spectrum of Bacampicillin Hydrochloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Bacampicillin Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> for chloride. D Optical rotation <2.49> [a]20: ＋140 – ＋1709(0.1 g calcu-lated on the anhydrous basis, ethanol (95), 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Amount [mg (potency)] of aztreonam (C ＝ MS × QT/QS × 250 13H17N5O8S2) Bacampicillin Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). MS: Amount [mg (potency)] of Aztreonam RS taken Internal standard solution—A solution of 4-aminobenzoic acid (1 in 6250).
storage conditions:
  en: Containers—Hermetic containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

bacitracin
type: ChemicalDrugMonograph
pref label:
  en: Bacitracin
  ja: バシトラシン
monograph id: JP18-bacitracin
publisher: JP
status: Official
version: 18
molecular formula: O16S
molecular weight: 1422.69
cas number: 22601-59-8
definition:
  en: Bacitracin A System performance: When the procedure is run with 10 mL of the standard solution under the above operating con- C66 H103 N17 O16S: 1422.69 ditions, ampicillin and the internal standard are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratio of the peak area of ampicillin to that of the internal standard is not more than 2.0z. Water <2.48> Not more than 1.0z (0.5 g, volumetric titra-tion, direct titration). Residue on ignition <2.44> Not more than 1.5z (1 g). Assay Weigh accurately an amount of Bacampicillin Hydrochloride and Bacampicillin Hydrochloride RS, equiva-lent to about 40 mg (potency), dissolve each in water to make exactly 100 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of bacampicillin in each solution. [22601-59-8] [1405-87-4, Bacitracin] Bacitracin is a mixture of peptide substances having antibacterial activity including bacitracin A as the main component produced by the growth of Bacillus subtilis or Bacillus licheniformis. It contains not less than 60 Units per mg, calculated on the dried basis.
appearance:
  en: Bacitracin occurs as a white to light brown powder. It is freely soluble in water, and slightly soluble in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 3 mL of a solution of Bacitracin (1 in 100) add 3 mL of 4-dimethylaminobenzaldehyde TS, shake until red-rosy to red-purple color appears, then add several drops of a solution of sodium nitrite (1 in 100), and Amount [ mg (potency)] of ampicillin (C H N O S) shake: a green to dark green color is produced. ＝ MS × AT/AS × 1000 16 19 3 4 (2) Dissolve 60 mg each of Bacitracin and Bacitracin RS in 10 mL of water, and use these solutions as the sample so- MS: Amount [mg (potency)] of Bacampicillin Hydrochlo-ride RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: To 500 mL of diluted 2 mol/L sodium dihy-drogen phosphate TS (1 in 100), add diluted 0.05 mol/L dis- lution and standard solution. Perform the test with these so-lutions as directed under Thin-layer Chromatography <2.03>. Spot 1 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. De-velop the plate with a mixture of 1-butanol, acetic acid (100), water, pyridine and ethanol (99.5) (30:15:10:6:5) to a dis-tance of about 10 cm, and air-dry the plate. Spray evenly ninhydrin TS on the plate, and heat the plate at 1109C for 5 minutes: the spots obtained from the sample solution and standard solution show the same Rf value.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Bacitracin according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 0.15 g of Bacitracin in 0.05 mol/L sulfuric acid TS to make 100 mL. To 2 mL of this solution add 0.05 mol/L sulfuric acid TS to make 10 mL, and determine the absorbances of this solution, A1 and A2, at 252 nm and 290 nm as directed under Ultraviolet-visible Spectrophotometry <2.24>: A2/A1 is not more than 0.20. ‌Loss on drying <2.41> Not more than 5.0z (1 g, in vacu-um, 609C, 3 hours). Residue on ignition <2.44> Not more than 1.0z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Bacampicillin Hydrochloride and Bacampicillin Hydrochloride RS, equiva-lent to about 40 mg (potency), dissolve each in water to make exactly 100 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of bacampicillin in each solution. [22601-59-8] [1405-87-4, Bacitracin] Bacitracin is a mixture of peptide substances having antibacterial activity including bacitracin A as the main component produced by the growth of Bacillus subtilis or Bacillus licheniformis. It contains not less than 60 Units per mg, calculated on the dried basis. The potency of Bacitracin is expressed as unit calculated from the amount of bacitracin A (C66H103N17O16S: 1422.69). One unit of Bacitracin is equivalent to 23.8 mg of bacitracin A (C66H103N17O16S). Description Bacitracin occurs as a white to light brown powder. It is freely soluble in water, and slightly soluble in ethanol (99.5). Identification (1) To 3 mL of a solution of Bacitracin (1 in 100) add 3 mL of 4-dimethylaminobenzaldehyde TS, shake until red-rosy to red-purple color appears, then add several drops of a solution of sodium nitrite (1 in 100), and Amount [ mg (potency)] of ampicillin (C H N O S) shake: a green to dark green color is produced. ＝ MS × AT/AS × 1000 16 19 3 4 (2) Dissolve 60 mg each of Bacitracin and Bacitracin RS in 10 mL of water, and use these solutions as the sample so- MS: Amount [mg (potency)] of Bacampicillin Hydrochlo-ride RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 25…
storage conditions:
  en: Containers—Tight containers. Storage—In a cold place.
type: PharmacopoeiaMonograph

baclofen
type: ChemicalDrugMonograph
pref label:
  en: Baclofen
  ja: バクロフェン
monograph id: JP18-baclofen
publisher: JP
status: Official
version: 18
molecular formula: C10H12ClNO2
molecular weight: 213.66
definition:
  en: Baclofen contains not less than 98.
appearance:
  en: Baclofen occurs as a white to pale yellow-white crystalline powder. It is freely soluble in acetic acid (100), slightly soluble in water, very slightly soluble in methanol and in ethanol (95), and practically insoluble in diethyl ether. It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Baclofen (1 in 1000) add 1 mL of ninhydrin TS, and heat on a water bath for 3 minutes: a blue-purple color develops. Determine the absorption spectrum of a solution of Baclofen in 0.1 mol/L hydrochloric acid TS (1 in 2000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Baclofen RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Perform the test with Baclofen as directed under Flame Coloration Test <1.04> (2): a green color appears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 0.5 g of Baclofen in 50 mL of acetic acid (100), and add water to make 100 mL. To 10 mL of this solution add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.30 mL of 0.01 mol/L hydrochloric acid VS add 5 mL of acetic acid (100), 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.21z). Heavy metals <1.07>—Proceed with 2.0 g of Baclofen according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Baclofen according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 50 mg of Baclofen in 50 mL of the mobile phase, and use this solution as the sam-ple solution. Pipet 1.0 mL and 1.5 mL of the sample solu-tion, to each add the mobile phase to make exactly 100 mL, and use these solutions as the standard solutions (1) and (2), respectively. Perform the test with exactly 25 mL each of the sample solution and standard solutions (1) and (2) as di-rected under Liquid Chromatography <2.01> according to the following conditions. Determine each peak height of these solutions: each height of the peaks other than the peak of baclofen obtained from the sample solution is not larger than the peak height of baclofen from the standard solution (1), and the total height of these peaks is not larger than the peak height of baclofen from the standard solution (2). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 268 nm). Column: A stainless steel column 4 mm in inside diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of methanol and diluted acetic acid (100) (1 in 900) (3:2). Flow rate: …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Baclofen, dissolve in 80 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue to greenish blue (indica-tor: 2 drops of crystal violet TS). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 21.37 mg of C10H12ClNO2
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

bakumondoto-extract
type: ChemicalDrugMonograph
pref label:
  en: Bakumondoto Extract
  ja: 麦門冬湯エキス
monograph id: JP18-bakumondoto-extract
publisher: JP
status: Official
version: 18
definition:
  en: Bakumondoto Extract contains not less than 1.
appearance:
  en: Bakumondoto Extract occurs as a light yellow to light brown powder or black-brown viscous extract. It has a slight odor, and a sweet taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Shake 2.0 g of the dry extract (or 6.0 g of the viscous extract) with 10 mL of water, add 5 mL of 1-butanol, shake, centrifuge, remove the 1-butanol layer, and use the aqueous layer as the sample solution. Separately, heat 3.0 g of pulverized ophiopogon root in 50 mL of water under a reflux condenser for 1 hour. After cooling, shake 20 mL of the extract with 5 mL of 1-butanol, centrifuge, re-move the 1-butanol layer, and use the aqueous layer as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 2 mL of the sample solution and 5 mL of the standard solution as bands on the original line on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethanol (99.5), water and acetic acid (100) (120:80:1) to a dis-tance of about 7 cm, and air-dry the plate. Spray evenly 4-methoxybenzaldehyde-sulfuric acid TS on the plate, and heat the plate at 1059C for 5 minutes: one of the several spots obtained from the sample solution has the same color tone and Rf value with the dark blue-green spot (Rf value: about 0.3) from the standard solution (Ophiopogon Root). Shake 5.0 g of the dry extract (or 15 g of the viscous extract) with 15 mL of water, add 5 mL of diethyl ether, shake, centrifuge, and use the diethyl ether layer as the sam-ple solution. Separately, dissolve 1 mg of cycloartenyl feru-late for thin-layer chromatography in 1 mL of ethyl acetate, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chro-matography <2.03>. Spot 30 mL of the sample solution and 5 mL of the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of hexane, acetone and acetic acid (100) (50:20:1) to a distance of about 7 cm, and air-dry the plate. Examine under ultravi-olet light (main wavelength: 365 nm): one of the several spots obtained from the sample solution has the same color …
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Prepare the test solution with 1.0 g of the dry extract (or an amount of the viscous extract, equivalent to 1.0 g of dried substance) as directed under Extracts (4), and perform the test (not more than 30 ppm). (2) Arsenic <1.11>—Prepare the test solution with 0.67 g of the dry extract (or an amount of the viscous extract, equivalent to 0.67 g of dried substance) according to Method 3, and perform the test (not more than 3 ppm). Loss on drying <2.41> The dry extract: Not more than 7.0z (1 g, 1059C, 5 hours). The viscous extract: Not more than 66.7z (1 g, 1059C, 5 hours). Total ash <5.01> Not more than 10.0z, calculated on the dried basis.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Ginsenoside Rb1—Weigh accurately about 2 g of the dry extract (or an amount of the viscous extract, equivalent to about 2 g of dried substance), add 30 mL of diluted methanol (3 in 5), shake for 15 minutes, centrifuge, and separate the supernatant liquid. To the residue add 15 mL of diluted methanol (3 in 5), and repeat the same proce-dure. Combine all of the supernatant liquid, and add diluted methanol (3 in 5) to make exactly 50 mL. Pipet 10 mL of this solution, add 3 mL of sodium hydroxide TS, allow to stand for 30 minutes, then add 3 mL of 1 mol/L hydrochloric acid TS, and add water to make exactly 20 mL. Apply exactly 5 mL of this solution to a column [about 10 mm in inside di-ameter, packed with 0.36 g of octadecylsilanized silica gel for pre-treatment (55 – 105 mm in particle size), and washed just before using with methanol and then diluted methanol (3 in 10)], and wash the column in sequence with 2 mL of diluted methanol (3 in 10), 1 mL of sodium carbonate TS and 10 mL of diluted methanol (3 in 10). Finally, elute with methanol to collect exactly 5 mL, and use this as the sample solution. Separately, weigh accurately about 10 mg of Gin-senoside Rb1 RS (separately determine the water <2.48> by coulometric titration, using 10 mg), and dissolve in methanol to make exactly 100 mL. Pipet 10 mL of this solution, add methanol to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine the peak areas, AT and AS, of ginsenoside Rb1 in each solution. ditions, the number of theoretical plates and the symmetry factor of the peak of ginsenoside Rb1 are not less than 5000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of t…
storage conditions:
  en: Containers—Tight containers.

bamethan-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Bamethan Sulfate
  ja: バメタン硫酸塩
monograph id: JP18-bamethan-sulfate
publisher: JP
status: Official
version: 18
definition:
  en: Bamethan Sulfate, when dried, contains not less than 99.
appearance:
  en: Bamethan Sulfate occurs as white, crystals or crystalline powder. It is odorless, and has a bitter taste. It is freely soluble in water and in acetic acid (100), soluble in methanol, slightly soluble in ethanol (95), and practically insoluble in diethyl ether. Melting point: about 1699C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of a solution of Bamethan Sulfate (1 in 1000) add 5 mL of a solution of 4-nitroben-zenediazonium fluoroborate (1 in 2000) and 10 mL of boric acid-potassium chloride-sodium hydroxide buffer solution (pH 9.2): an orange-red color develops. Determine the absorption spectrum of a solution of Bamethan Sulfate in 0.01 mol/L hydrochloric acid TS (1 in 10,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Bamethan Sulfate, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>: it exhibits absorption at the wave numbers of about 1618, 1597, 1518, 1118 and 833 cm－1. A solution of Bamethan Sulfate (1 in 100) responds to Qualitative Tests <1.09> for sulfate. spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.75 g of Bamethan Sulfate, previously dried, dissolve in 80 mL of acetic acid (100), and titrate with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 51.67 mg of (C12H19NO2)2.H2SO4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

barbital
type: ChemicalDrugMonograph
pref label:
  en: Barbital
  ja: バルビタール
monograph id: JP18-barbital
publisher: JP
status: Official
version: 18
molecular formula: C8H12N2O3
molecular weight: 184.19
definition:
  en: Barbital, when dried, contains not less than 99.
appearance:
  en: Barbital occurs as colorless or white crystals or a white crystalline powder. It is odorless, and has a slightly bitter taste. ‌JP XVIII Official Monographs / Barium Sulfate 513 It is freely soluble in acetone and in pyridine, soluble in ethanol (95), sparingly soluble in diethyl ether, and slightly soluble in water and in chloroform. It dissolves in sodium hydroxide TS and in ammonia TS. The pH of its saturated solution is between 5.0 and 6.0.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Boil 0.2 g of Barbital with 10 mL of sodium hydroxide TS: the gas evolved changes moistened red litmus paper to blue. Dissolve 0.05 g of Barbital in 5 mL of diluted pyri-dine (1 in 10), add 0.3 mL of copper (II) sulfate TS, shake, and allow to stand for 5 minutes: a red-purple precipitate is formed. Shake the mixture with 5 mL of chloroform: a red-purple color develops in the chloroform layer. Separately, dissolve 0.05 g of Barbital in 2 to 3 drops of ammonia-ammonium chloride buffer solution (pH 10.7) and 5 mL of diluted pyridine (1 in 10). Add 5 mL of chloroform and 0.3 mL of copper (II) sulfate TS to the solution: a red-purple precipitate is produced in the aqueous layer. The red-purple precipitate is not dissolved in the chloroform by shaking. To 0.4 g of Barbital add 0.1 g of anhydrous sodium carbonate and 4 mL of water, shake, and add a solution of 0.3 g of 4-nitrobenzyl chloride in 7 mL of ethanol (95). Heat the mixture on a water bath under a reflux condenser for 30 minutes, and allow to stand for 1 hour. Collect the separated crystals, wash with 7 mL of sodium hydroxide TS and a small amount of water, recrystallize from a mixture of ethanol (95) and chloroform (1:1), and dry at 1059C for 30 minutes: the crystals melt <2.60> between 1929C and 1969C.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g Description Barbital occurs as colorless or white crystals or a white crystalline powder. It is odorless, and has a slightly bitter taste. ‌JP XVIII Official Monographs / Barium Sulfate 513 It is freely soluble in acetone and in pyridine, soluble in ethanol (95), sparingly soluble in diethyl ether, and slightly soluble in water and in chloroform. It dissolves in sodium hydroxide TS and in ammonia TS. The pH of its saturated solution is between 5.0 and 6.0. Identification (1) Boil 0.2 g of Barbital with 10 mL of sodium hydroxide TS: the gas evolved changes moistened red litmus paper to blue. Dissolve 0.05 g of Barbital in 5 mL of diluted pyri-dine (1 in 10), add 0.3 mL of copper (II) sulfate TS, shake, and allow to stand for 5 minutes: a red-purple precipitate is formed. Shake the mixture with 5 mL of chloroform: a red-purple color develops in the chloroform layer. Separately, dissolve 0.05 g of Barbital in 2 to 3 drops of ammonia-ammonium chloride buffer solution (pH 10.7) and 5 mL of diluted pyridine (1 in 10). Add 5 mL of chloroform and 0.3 mL of copper (II) sulfate TS to the solution: a red-purple precipitate is produced in the aqueous layer. The red-purple precipitate is not dissolved in the chloroform by shaking. To 0.4 g of Barbital add 0.1 g of anhydrous sodium carbonate and 4 mL of water, shake, and add a solution of 0.3 g of 4-nitrobenzyl chloride in 7 mL of ethanol (95). Heat the mixture on a water bath under a reflux condenser for 30 minutes, and allow to stand for 1 hour. Collect the separated crystals, wash with 7 mL of sodium hydroxide TS and a small amount of water, recrystallize from a mixture of ethanol (95) and chloroform (1:1), and dry at 1059C for 30 minutes: the crystals melt <2.60> between 1929C and 1969C. Melting point <2.60> 189 – 1929C Purity (1) Clarity and color of solution—Dissolve 0.5 g of Barbital in 5 mL of sodium hydroxide TS: the solution is clear and colorless. Chloride <1.03>—Dissolv…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Barbital, previously dried, and dissolve in 5 mL of ethanol (95) and 50 mL of chloroform. Titrate <2.50> with 0.1 mol/L potassium hy-droxide-ethanol VS until the color of the solution changes from yellow through light blue to purple (indicator: 1 mL of alizarin yellow GG-thymolphthalein TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L potassium hydroxide-ethanol VS ＝ 18.42 mg of C8H12N2O3
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

barium-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Barium Sulfate
  ja: 硫酸バリウム
monograph id: JP18-barium-sulfate
publisher: JP
status: Official
version: 18
molecular formula: BaSO4
molecular weight: 233.39
appearance:
  en: Barium Sulfate occurs as a white powder. It is odorless and tasteless. It is practically insoluble in water, in ethanol (95) and in diethyl ether. It does not dissolve in hydrochloric acid, in nitric acid and in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Mix 0.5 g of Barium Sulfate with 2 g each of anhydrous sodium carbonate and potassium carbon-ate in a crucible, heat the mixture until fusion is complete, treat the cooled mass with hot water, and filter. The filtrate, acidified with hydrochloric acid, responds to Qualitative Tests <1.09> for sulfate. (2) Wash the hot water-insoluble residue obtained in (1) with water, dissolve in 2 mL of acetic acid (31), and filter, if necessary: the solution responds to Qualitative Tests <1.09> for barium salt.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity or alkalinity—Agitate 1.0 g of Barium Sulfate with 20 mL of water for 5 minutes: the solution is neutral. Phosphate—Boil 1.0 g of Barium Sulfate with 3 mL of nitric acid and 5 mL of water for 5 minutes, cool, and add water to restore the original volume. Filter through a filter paper, previously washed with dilute nitric acid, to the fil-trate add an equal volume of hexaammonium heptamolyb-date TS, and allow to stand between 509C and 609C for 1 hour: no yellow precipitate is produced. Sulfide—Place 10 g of Barium Sulfate in a 250-mL conical flask, add 10 mL of dilute hydrochloric acid and water to make 100 mL, and boil for 10 minutes: the gas evolved does not darken moistened lead (II) acetate paper. Heavy metals <1.07>—Boil 5.0 g of Barium Sulfate with 2.5 mL of acetic acid (100) and 50 mL of water for 10 minutes, cool, add 0.5 mL of ammonia TS and water to make 100 mL, and filter. Perform the test with a 50-mL por-tion of this filtrate. Prepare the control solution with 2.5 mL of Standard Lead Solution, 1.25 mL of acetic acid (100), 0.25 mL of ammonia TS and water to make 50 mL (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 2.0 g of Barium Sulfate according to Method 1, and perform the test (not more than 1 ppm). Hydrochloric acid-soluble substances and soluble barium salts—Cool the solution obtained in (3), add water to make 100 mL, and filter. Evaporate 50 mL of the filtrate on a water bath to dryness, add 2 drops of hydrochloric acid and 10 mL of warm water, filter through a filter paper for quantitative analysis, and wash with 10 mL of warm water. Evaporate the combined filtrate and washings on a water bath to dryness, and dry the residue at 1059C for 1 hour: the residue weighs not more than 15 mg. Shake the residue, if any, with 10 mL of water, and filter. To the filtrate add 0.5 mL of dilute sulfuric acid, and allow to stand for 30 minutes: no turbidity is produced. ‌514‌
storage conditions:
  en: Containers—Well-closed contain-ers.

beclometasone-dipropionate
type: ChemicalDrugMonograph
pref label:
  en: Beclometasone Dipropionate
  ja: ベクロメタゾンプロピオン酸エステル
monograph id: JP18-beclometasone-dipropionate
publisher: JP
status: Official
version: 18
molecular formula: C28H37ClO7
molecular weight: 521.04
cas number: 5534-09-8
definition:
  en: Beclometasone Dipropionate, when dried, contains not less than 97.
appearance:
  en: Beclometasone Dipropionate occurs as a white to pale yellow powder. It is soluble in methanol, sparingly soluble in ethanol cording to the following conditions, and calculate the ratios, QT and QS, of the peak area of beclometasone dipropionate to that of the internal standard, respectively. (99.5), and practically insoluble in water. Melting point: about 2089C (with decomposition). It shows crystal polymorphism. Amount (mg) of beclometasone dipropionate (C ＝ MS × QT/QS 28H 37ClO7)
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 2 mg of Beclometasone Dipropionate in 2 mL of sulfuric acid: initially a yellowish color develops, and gradually changes through orange to dark red-brown. To this solution add carefully 10 mL of water: the color changes to bluish green, and a flocculent precipitate is formed. Dissolve 0.01 g of Beclometasone Dipropionate in 1 mL of methanol, add 1 mL of Fehling's TS, and heat: a red to red-brown precipitate is formed. Perform the test with 0.02 g of Beclometasone Dipropionate as directed under Oxygen Flask Combustion Method <1.06>, using a mixture of 1 mL of sodium hydrox-ide TS and 20 mL of water as an absorbing liquid: the test solution responds to Qualitative Tests <1.09> for chloride. Determine the infrared absorption spectrum of Beclometasone Dipropionate, previously dried, as directed in MS: Amount (mg) of Beclometasone Dipropionate RS taken Internal standard solution—A solution of testosterone propionate in methanol (1 in 4000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 20 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of acetonitrile and water (3:2). Flow rate: Adjust so that the retention time of beclometa- sone dipropionate is about 6 minutes. ‌JP XVIII Official Monographs / Bekanamycin Sulfate 515 System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, beclometasone dipropionate and the internal stand-ard are eluted in this order with the resolution between these peaks being not less than 8. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of beclometasone dipro…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 0.5 g of Beclometasone Dipropionate according to Method 2, and perform the test. Prepare the control solution with 1.5 mL of Standard Lead Solution (not more than 30 ppm). (2) Related substances—Dissolve 20 mg of Beclometa-sone Dipropionate in 5 mL of a mixture of chloroform and methanol (9:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of chlo-roform and methanol (9:1) to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 1,2-dichloroethane, methanol and water (475:25:1) to a distance of about 15 cm, and air-dry the plate. Spray evenly alkaline blue tetrazolium TS on the plate: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (0.5 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (0.5 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 20 mg each of Beclometa-sone Dipropionate and Beclometasone Dipropionate RS, previously dried, and dissolve each in methanol to make exactly 50 mL. Pipet 10 mL each of these solutions, add exactly 10 mL of the internal standard solution and metha-nol to make 50 mL, and use these solutions as the sample so-lution and the standard solution, respectively. Perform the beclometasone dipropionate (C 28H 37ClO7). test with 20 mL each of the sample solution and standard so- lution as directed under Liquid Chromatography <2.01> ac- Description Beclometasone Dipropionate occurs as a white to pale yellow powder. It is soluble in methanol, sparingly soluble in ethanol cording to the following conditions, and calculate the ratios, QT and QS, of the peak area of beclometasone dipropionate to that of the internal standard, respectively. (99.5), and practically insoluble in water. Melting point: about 2089C (with decomposition). It shows crystal polymorphism. Amount (mg) of beclometasone dipropionate (C ＝ MS × QT/QS 28H 37ClO7) Identification (1) Dissolve 2 mg of Beclometasone Dipropionate in 2 mL of sulfuric acid: initially a yellowish color develops, and gradually changes through orange to dark red-brown. To this solution add carefully 10 mL of water: the color changes to bluish green, and a flocculent precipitate is formed. Dissolve 0.01 g of Beclometasone Dipropionate in 1 mL of methanol, add 1 mL of Fehling's TS, and heat: a red to red-brown precipitate is formed. Perform the test with 0.02 g of Beclometasone Dipropionate as directed under Oxygen Flask Combustion Method <1.06>, using a mixture of 1 mL of sodium hydrox-ide TS and 20 mL of water as an absorbing liquid: the test solution responds to Qualitative Tests <1.09> for chloride. Determine the infrared absorption spectrum of Beclometasone Dipropionate, previously dried, as directed in MS: Amount (mg) of Beclometasone Dipropionate RS taken Internal standard solution—A solution of testosterone propion…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bekanamycin-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Bekanamycin Sulfate
  ja: ベカナマイシン硫酸塩
monograph id: JP18-bekanamycin-sulfate
publisher: JP
status: Official
version: 18
appearance:
  en: Bekanamycin Sulfate occurs as a white pow-der. It is freely soluble in water, and practically insoluble in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 20 mg of Bekanamycin Sulfate in 2 mL of 1/15 mol/L phosphate buffer solution (pH 5.6), add 1 mL of ninhydrin TS, and boil: a blue-purple color develops. Dissolve 30 mg each of Bekanamycin Sulfate and Bekanamycin Sulfate RS in 5 mL of water, and use these solutions as the sample solution and standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a solu-tion of potassium dihydrogen phosphate (3 in 40) to a dis-tance of about 10 cm, and air-dry the plate. Spray evenly 0.2z ninhydrin-water saturated 1-butanol TS on the plate, and heat the plate at 1009C for 10 minutes: the principal spots obtained from the sample solution and the standard solution show a purple-brown color and the same Rf value. To a solution of Bekanamycin Sulfate (1 in 5) add 1 drop of barium chloride TS: a white turbidity is produced. D Optical rotation <2.49> [a]20: ＋102 – ＋1169(after drying, 0.25 g, water, 25 mL, 100 mm). pH <2.54> The pH of a solution obtained by dissolving 0.50 g of Bekanamycin Sulfate in 10 mL of water is between 6.0 and 8.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Bekanamycin Sulfate in 5 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Bekana- mycin Sulfate according to Method 4, and perform the test. Prepare the control solution with 3.0 mL of Standard Lead Solution (not more than 30 ppm). Arsenic <1.11>—Prepare the test solution with 2.0 g of Bekanamycin Sulfate according to Method 1, and per-form the test (not more than 1 ppm). Related substances—Dissolve 60 mg of Bekanamycin Sulfate in 10 mL of water, and use this solution as the sam-ple solution. Pipet 3 mL of the sample solution, add water to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a solution of potassium dihydrogen phosphate (3 in 40) to a distance of about 10 cm, and air-dry the plate. Spray evenly 0.2z ninhydrin-water saturated 1-butanol TS on the plate, and heat the plate at 1009C for 10 minutes: the spot other than the principal spot obtained from the sample solution is not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 5.0z (0.5 g, reduced pressure not exceeding 0.67 kPa, 609C, 3 hours). Residue on ignition <2.44> Not more than 0.5z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform the test according to the Cylinder-plate method as directed under Microbial Assay for Antibiotics <4.02> according to the following conditions. Test organism—Bacillus subtilis ATCC 6633 Culture medium—Use the medium i in 1) under (1) Agar media for seed and base layer having pH <2.54> 7.8 to 8.0 after sterilization. Standard solutions—Weigh accurately an amount of Bekanamycin Sulfate RS, previously dried, equivalent to about 20 mg (potency), dissolve in diluted phosphate buffer solution (pH 6.0) (1 in 2) to make exactly 50 mL, and use this solution as the standard stock solution. Keep the stand-ard stock solution at 5 to 159C and use within 30 days. Take exactly a suitable amount of the standard stock solution before use, add 0.1 mol/L phosphate buffer solution (pH 8.0) to make solutions so that each mL contains 10 mg (po-tency) and 2.5 mg (potency), and use these solutions as the high concentration standard solution and low concentration standard solution, respectively. Sample solutions—Weigh accurately an amount of Bekanamycin Sulfate, equivalent to about 20 mg (potency), and dissolve in water to make exactly 50 mL. Take exactly a suitable amount of this solution, add 0.1 mol/L phosphate buffer solution (pH 8.0) to make solutions so that each mL contains 10 mg (potency) and 2.5 mg (potency), and use these solutions as the high concentration sample solution and low concentration sample solution, respectively. ‌516
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

belladonna-extract
type: ChemicalDrugMonograph
pref label:
  en: Belladonna Extract
  ja: ベラドンナエキス
monograph id: JP18-belladonna-extract
publisher: JP
status: Official
version: 18
definition:
  en: Belladonna Extract contains not less than 0.
appearance:
  en: Belladonna Extract has a dark brown color, a characteristic odor and a bitter taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Mix 0.5 g of Belladonna Extract with 30 mL of ammonia TS in a flask, transfer the mixture to a separa-tor, then add 40 mL of ethyl acetate, and shake the mixture. Drain off the ethyl acetate layer, add 3 g of anhydrous so-dium sulfate to the ethyl acetate, shake, and filter after the ethyl acetate becomes clear. Evaporate the solvent to dryness under low pressure (in vacuo), dissolve the residue in 1 mL of ethanol (95), and use this solution as the sample solution. Proceed as directed in the Identification under Belladonna Root.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Heavy metals <1.07>—Prepare the test solution with 1.0 g of Belladonna Extract as directed under the Extracts (4), and perform the test (not more than 30 ppm).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Belladonna Extract, place in a glass-stoppered centrifuge tube, add 15 mL of am-monia TS, and shake. Add 25 mL of diethyl ether, stopper tightly, shake for 15 minutes, centrifuge, and separate the diethyl ether layer. Repeat this procedure twice with the aqueous layer, using 25 mL each of diethyl ether. Combine the extracts, and evaporate the solvent on a water bath. Dis-solve the residue in 5 mL of the mobile phase, add exactly 3 mL of the internal standard solution, and add the mobile phase to make exactly 25 mL. Proceed as directed under Bel-ladonna Root. Amount (mg) of hyoscyamine (C17H23NO3) ＝ MS × QT/QS × 1/5 × 0.855 MS: Amount (mg) of Atropine Sulfate RS taken, calcu-lated on the dried basis Internal standard solution—A solution of brucine dihydrate in the mobile phase (1 in 2500).
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant, and in a cold place.

belladonna-total-alkaloids
type: ChemicalDrugMonograph
pref label:
  en: Belladonna Total Alkaloids
  ja: ベラドンナ総アルカロイド
monograph id: JP18-belladonna-total-alkaloids
publisher: JP
status: Official
version: 18
definition:
  en: Belladonna Total Alkaloids contains not less than 95.
appearance:
  en: Belladonna Total Alkaloids occurs as white, crystals or crystalline powder. It is very soluble in methanol, freely soluble in ethanol (99.5), and slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Dissolve 2 mg of Belladonna Total Alkaloids in 1 mL of ethanol (95), and use this solution as the sample solution. Then proceed as directed in the Identification under Belladonna Root. D Optical rotation <2.49> [a]20: －18.5 – －22.09(after dry-ing, 1 g, ethanol (99.5), 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Place 1.0 g of Bella-donna Total Alkaloids in a porcelain crucible, and mix with 1.2 mL of dilute hydrochloric acid. Mix with 10 mL of a so-lution of magnesium nitrate hexahydrate in ethanol (95) (1 in 10), and after evaporating the solvent on a boiling water bath, carbonize by gradual heating. Then proceed according to Method 4, and perform the test. The control solution is prepared as follows: Mix 1.2 mL of dilute hydrochloric acid with 10 mL of a solution of magnesium nitrate hexahydrate in ethanol (95) (1 in 10), and evaporate the solvent on a boil-ing water bath. After cooling, add 1 mL of sulfuric acid, then proceed according to Method 4, and add 2.0 mL of Standard Lead Solution and water to make 50 mL (not more than 20 ppm). (2) Arsenic <1.11>—Prepare the test solution with 2.0 g of Belladonna Total Alkaloids according to Method 4, and perform the test (not more than 1 ppm). Loss on drying <2.41> Not more than 1.0z (1 g, in vacu-um, 609C, 6 hours). Residue on ignition <2.44> Not more than 0.2z (0.5 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 25 mg of Belladonna Total Alkaloids, and dissolve in methanol to make exactly 25 mL. Pipet 5 mL of this solution, add exactly 3 mL of the internal standard solution and the mobile phase to make 25 mL, and use this solution as the sample solution. Separately, weigh accurately about 25 mg of Atropine Sulfate RS (separately determine the loss on drying <2.41> under the same condi-tions as Atropine Sulfate Hydrate), dissolve in the mobile phase to make exactly 25 mL, and use this solution as the standard stock solution (1). Also, weigh accurately about 25 mg of Scopolamine Hydrobromide RS (separately determine the loss on drying <2.41> under the same conditions as Scopolamine Hydrobromide Hydrate), and dissolve in the mobile phase to make exactly 25 mL. Pipet 3 mL of this so-lution, add the mobile phase to make exactly 25 mL, and use this solution as the standard stock solution (2). Take exactly 5 mL of standard stock solution (1), add exactly 2 mL of the ‌JP XVIII Crude Drugs and Related Drugs / Benincasa Seed 1959 standard stock solution (2), and add exactly 3 mL of the in-ternal standard solution. To this solution add the mobile phase to make 25 mL, and use this solution as the standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi-tions, and calculate the ratios, QTA and QSA, of the peak area of hyoscyamine (atropine) to that of the internal standard and the ratios, QTS and QSS, of the peak area of scopolamine to that of the internal standard. Then calculate the amounts of hyoscyamine and scopolamine using the following equa-tions. The amount of the total alkaloids is obtained as the sum of them. Benincasa Seed Benincasae Semen

benidipine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Benidipine Hydrochloride
  ja: ベニジピン塩酸塩
monograph id: JP18-benidipine-hydrochloride
publisher: JP
status: Official
version: 18
cas number: 91599-74-5
definition:
  en: Benidipine Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Benidipine Hydrochloride occurs as a yellow crystalline powder. It is very soluble in formic acid, soluble in methanol, sparingly soluble in ethanol (99.5), and practically insoluble in water. A solution of Benidipine Hydrochloride in methanol (1 in 100) shows no optical rotation. Melting point: about 2009C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Benidipine Hydrochloride in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Benidipine Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. To 5 mL of a solution of Benidipine Hydrochloride (1 in 10) add 5 mL of ammonia TS, heat on a water bath for 5 minutes, cool, and filter. The filtrate, which is acidified with dilute nitric acid, responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Benidipine Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 20 mg of Benidipine Hydrochloride in 100 mL of a mixture of water and metha-nol (1:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mixture of water and methanol (1:1) to make exactly 500 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine each peak area by the automatic integration method: the peak areas of bisbenzyl-piperidyl ester having the relative retention time of about 0.35 to benidipine, dehydro derivative having the relative retention time of about 0.75 and other related substances obtained from the sample solution are not larger than 1/2 times the peak area of benidipine from the standard solu-tion, and the total area of the peaks other than benidipine from the sample solution is not larger than the peak area of benidipine from the standard solution. For the areas of the peaks of bisbenzylpiperidyl ester and dehydro derivative, multiply their correction factor 1.6, respectively. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 237 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 10 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of 0.05 mol/L potassium dihy-drogen phosphate TS (pH 3.0), methanol and tetrahydrofu-ran (65:27:8). Flow rate: Adjust so that the retention time of benidipine is about 20 minutes. Time span of measurement: About 2 times as long as the retention time of benidipine, beginning…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.7 g of Benidipine Hydro-chloride, previously dried, dissolve in 10 mL of formic acid, add 70 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 54.20 mg of C28H31N3O6.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

benoxinate-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Benoxinate Hydrochloride
  ja: オキシブプロカイン塩酸塩
monograph id: JP18-benoxinate-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C17H28N2O3.HCl
molecular weight: 344.88
cas number: 5987-82-6
appearance:
  en: Oxybuprocaine Hydrochloride occurs as white, crystals or crystalline powder. It is odorless, and has a saline taste. It exhibits anesthetic properties when placed on the tongue. It is very soluble in water, freely soluble in ethanol (95) and in chloroform, and practically insoluble in diethyl ether. The pH of a solution of 1.0 g of Oxybuprocaine Hydro- chloride in 10 mL of water is between 5.0 and 6.0. It is gradually colored by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 10 mg of Oxybuprocaine Hy-drochloride in 1 mL of dilute hydrochloric acid and 4 mL of water. This solution responds to Qualitative Tests <1.09> for primary aromatic amines. Dissolve 0.1 g of Oxybuprocaine Hydrochloride in 8 mL of water, and add 3 mL of ammonium thiocyanate TS: an oily substance is produced. Rub the inner surface of the container with a glass rod: white crystals are formed. Collect the crystals so obtained, recrystallize from water, and dry in a desiccator (in vacuum, phosphorus (V) oxide) for 5 hours: the crystals melt <2.60> between 1039C and 1069C. Determine the absorption spectrum of a solution of Oxybuprocaine Hydrochloride (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. A solution of Oxybuprocaine Hydrochloride (1 in 10) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Oxybuprocaine Hydrochloride in 10 mL of water: the so-lution is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Oxybu- procaine Hydrochloride according to Method 1, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.25 g of Oxybu-procaine Hydrochloride in 10 mL of chloroform, and use this solution as the sample solution. Pipet 1 mL of the sam-ple solution, and add chloroform to make exactly 20 mL. Pipet 1 mL of this solution, add chloroform to make exactly 50 mL, and use this solution as the standard solution. Per-form the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform, ethanol (95) and formic acid (7:2:1) to a dis-tance of about 10 cm, and air-dry the plate. Spray evenly 4-dimethylaminobenzaldehyde TS for spraying on the plate: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Oxybuprocaine Hy-drochloride, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 34.49 mg of C17H28N2O3.HCl
storage conditions:
  en: Containers—Well-closed contain-
type: PharmacopoeiaMonograph

benserazide-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Benserazide Hydrochloride
  ja: ベンセラジド塩酸塩
monograph id: JP18-benserazide-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C10H15N3O5.HCl
molecular weight: 293.7
cas number: 14919-77-8
definition:
  en: Benserazide Hydrochloride contains not less than 98.
appearance:
  en: Benserazide Hydrochloride occurs as a white to grayish white crystalline powder. It is freely soluble in water and in formic acid, soluble in methanol, very slightly soluble in ethanol (95). It dissolves in 0.1 mol/L hydrochloric acid TS. The pH of a solution of 1.0 g of Benserazide Hydrochlo-ride in 100 mL of water is between 4.0 and 5.0. It is hygroscopic. It is gradually colored by light. A solution of Benserazide Hydrochloride (1 in 100) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Benserazide Hydrochloride in 0.1 mol/L hydro-chloric acid TS (1 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Ben-serazide Hydrochloride as directed in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. To 10 mL of a solution of Benserazide Hydrochloride (1 in 30) add silver nitrate TS: a white precipitate is formed. To a portion of this precipitate add dilute nitric acid: the precipitation does not dissolve.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Benserazide Hydrochloride in 10 mL of water, and per-form the test with this solution as directed under Ultraviolet-visible Spectrophotometry <2.24>: the absorbance of this so-lution at 430 nm is not more than 0.10. Heavy metals <1.07>—Proceed with 1.0 g of Benser- azide Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 0.25 g of Benserazide Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL and 3 mL of the sample solution, add methanol to make exactly 200 mL, and use these solutions as the standard solution (1) and (2), respectively. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 2 mL each of the sample solution and standard solutions (1) and (2) on a plate of cellulose for thin-layer chromatogra- ‌JP XVIII Official Monographs / Benzalkonium Chloride 519‌ phy. Develop the plate with a solution of formic acid in so-dium chloride TS (1 in 1000) to a distance of about 10 cm, and air-dry the plate. Spray evenly sodium carbonate TS, air-dry, and then spray evenly Folin's TS on the plate: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the stand-ard solution (2), and the number of the spots which intense more than the spot from the standard solution (1) are not more than 2. Water <2.48> Not more than 2.5z (0.5 g, volumetric titra-tion, direct titration). Use a solution of salicylic acid in methanol for water determination (3 in 20) instead of metha-nol for water determination. Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Benserazide Hydro-chloride, dissolve in 5 mL of formic acid, add 50 mL of ace-tic acid (100), and titrate <2.50> immediately with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 29.37 mg of C10H15N3O5.HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

bentonite
type: ChemicalDrugMonograph
pref label:
  en: Bentonite
  ja: ベントナイト
monograph id: JP18-bentonite
publisher: JP
status: Official
version: 18
appearance:
  en: Bentonite occurs as a very fine, white to light yellow-brown powder. It is odorless. It has a slightly earthy taste. It is practically insoluble in water, in ethanol (95) and in diethyl ether. It swells in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Add 0.5 g of Bentonite to 3 mL of diluted sulfuric acid (1 in 3), and heat until white fumes are evolved. Cool, add 20 mL of water, and filter. To 5 mL of the filtrate add 3 mL of ammonia TS: a white, gelatinous precipitate is produced, which turns red on the addition of 5 drops of alizarin red S TS. (2) Wash the residue obtained in (1) with water, add 2 mL of a solution of methylene blue trihydrate (1 in 10,000), and wash again with water: the residue is blue in color. pH <2.54> To 1.0 g of Bentonite add 50 mL of water, and shake: the pH of the suspension is between 9.0 and 10.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—To 1.5 g of Bentonite add 80 mL of water and 5 mL of hydrochloric acid, and boil gently for 20 minutes with thorough stirring. Cool, centri-fuge, collect the supernatant liquid, wash the residue with two 10-mL portions of water, and centrifuge each. Combine the supernatant liquid and the washings, and add dropwise ammonia solution (28). When a precipitate is produced, add dropwise dilute hydrochloric acid with vigorous stirring, and dissolve. To the solution add 0.45 g of hydroxylammonium chloride, and heat. Cool, and add 0.45 g of sodium acetate trihydrate, 6 mL of dilute acetic acid and water to make 150 mL. Pipet 50 mL of the solution, and perform the test using this solution as the test solution. Prepare the control solution as follows: mix 2.5 mL of Standard Lead Solution, 0.15 g of hydroxylammonium chloride, 0.15 g of sodium acetate trihy-drate, and 2 mL of dilute acetic acid, and add water to make 50 mL (not more than 50 ppm). Arsenic <1.11>—To 1.0 g of Bentonite add 5 mL of dilute hydrochloric acid, and gently heat to boil while stir-ring well. Cool immediately, and centrifuge. To the residue add 5 mL of dilute hydrochloric acid, shake well, and centri-fuge. To the residue add 10 mL of water, and perform the same operations. Combine all the extracts, and heat on a water bath to concentrate to 5 mL. Perform the test with this solution as the test solution (not more than 2 ppm). Foreign matter—Place 2.0 g of Bentonite in a mor-tar, add 20 mL of water to swell, disperse evenly with a pes-tle, and dilute with water to 100 mL. Pour the suspension through a No. 200 (74 mm) sieve, and wash the sieve thor-oughly with water. No grit is felt when the fingers are rubbed over the wire mesh of the sieve. Loss on drying <2.41> 5.0 – 10.0z (2 g, 1059C, 2 hours). Gel formation Mix 6.0 g of Bentonite with 0.30 g of mag-nesium oxide. Add the mixture, in several portions, to 200 mL of water contained in a glass-stoppered 500-mL cylinder. Agitate for 1 h…
storage conditions:
  en: Containers—Well-closed contain-ers.

benzalkonium-chloride
type: ChemicalDrugMonograph
pref label:
  en: Benzalkonium Chloride
  ja: ベンザルコニウム塩化物
monograph id: JP18-benzalkonium-chloride
publisher: JP
status: Official
version: 18
definition:
  en: Benzalkonium Chloride is represented by the for mula [C6H5CH2N(CH3)2R]Cl, in which R extends from C8H17 to C18H37, with C12H25 and C14H29 com-prising the major portion. It contains not less than 95.
appearance:
  en: Benzalkonium Chloride occurs as a white to yellow-white powder, colorless to light yellow, gelatinous pieces, or jelly-like fluid or mass. It has a characteristic odor. It is very soluble in water and in ethanol (95), and practi-cally insoluble in diethyl ether. A solution of Benzalkonium Chloride foams strongly when shaken.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.2 g of Benzalkonium Chlo-ride in 1 mL of sulfuric acid, add 0.1 g of sodium nitrate, and heat for 5 minutes on a water bath. After cooling, add 10 mL of water and 0.5 g of zinc powder, heat for 5 minutes, cool, and filter: the filtrate responds to Qualitative Tests <1.09> for primary aromatic amines. The color of the solu- tion is red. To 2 mL of a solution of Benzalkonium Chloride (1 in 1000) add a mixture of 0.2 mL of a solution of bromophe-nol blue (1 in 2000) and 0.5 mL of sodium hydroxide TS: a blue color develops. Add 4 mL of chloroform to this solu-tion, and shake vigorously: the blue color shifts to the chlo-roform layer. Collect the chloroform layer, and add drop-wise, with stirring, a solution of sodium lauryl sulfate (1 in 1000): the chloroform layer turns colorless. Determine the absorption spectrum of a solution of Benzalkonium Chloride in 0.1 mol/L hydrochloric acid TS (1 in 2000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. ‌To 1 mL of a solution of Benzalkonium Chloride (1 in 100) add 2 mL of ethanol (95), 0.5 mL of dilute nitric acid and 1 mL of silver nitrate TS: a white precipitate is pro-duced. This precipitate does not dissolve on the addition of dilute nitric acid, but dissolves on the addition of ammonia TS.‌
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Benzalkonium Chloride in 10 mL of water: the solution is clear and colorless to light yellow. (2) Petroleum ether-soluble substances—To 3.0 g of Benzalkonium Chloride add water to make 50 mL, then add 50 mL of ethanol (99.5) and 5 mL of 0.5 mol/L sodium hy- It foams strongly on shaking. Identification (1) Evaporate a volume of Benzalkonium Chloride Solution, equivalent to 0.2 g of Benzalkonium Chloride, on a water bath to dryness, and proceed with the residue as directed in the Identification (1) under Benzalko-nium Chloride. To a volume of Benzalkonium Chloride Solution, equivalent to 0.01 g of Benzalkonium Chloride, add water to make 10 mL. Proceed with 2 mL of this solution as directed in the Identification (2) under Benzalkonium Chloride. To a volume of Benzalkonium Chloride Solution, equivalent to 1 g of Benzalkonium Chloride, add water or concentrate on a water bath, if necessary, to make 10 mL. To 1 mL of this solution add 0.1 mol/L hydrochloric acid VS to make 200 mL, and proceed as directed in the Identifi-cation (3) under Benzalkonium Chloride. To a volume of Benzalkonium Chloride Solution, equivalent to 0.1 g of Benzalkonium Chloride, add water or concentrate on a water bath, if necessary, to make 10 mL. Proceed with 1 mL of this solution as directed in the Identifi-cation (4) under Benzalkonium Chloride.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Pipet a volume of Benzalkonium Chloride Solution, equivalent to about 0.15 g of benzalkonium chloride droxide TS, and extract with three 50-mL portions of petro- leum ether. Combine the petroleum ether extracts, and wash (C22H ClN), dilute with water to make 75 mL, if necessary, with three 50-mL portions of dilute ethanol. After shaking well with 10 g of anhydrous sodium sulfate, filter through a dry filter paper, and wash the filter paper with two 10-mL portions of petroleum ether. Evaporate the petroleum ether on a water bath by heating, and dry the residue at 1059C for 1 hour: the residue is not more than 1.0z. Water <2.48> Not more than 15.0z (volumetric titration, direct titration). Residue on ignition <2.44> Not more than 0.2z (1 g). Assay Weigh accurately about 0.15 g of Benzalkonium Chloride, and dissolve in 75 mL of water. Adjust the pH be-tween 2.6 and 3.4 by adding dropwise diluted dilute hydro-chloric acid (1 in 2), add 1 drop of methyl orange TS, and titrate <2.50> with 0.02 mol/L sodium tetraphenylboron VS until the color of the solution becomes red. Each mL of 0.02 mol/L sodium tetraphenylboron VS and proceed as directed in the Assay under Benzalkonium Chloride. Each mL of 0.02 mol/L sodium tetraphenylboron VS ＝ 7.080 mg of C22H40ClN
storage conditions:
  en: Containers—Tight containers.

benzbromarone
type: ChemicalDrugMonograph
pref label:
  en: Benzbromarone
  ja: ベンズブロマロン
monograph id: JP18-benzbromarone
publisher: JP
status: Official
version: 18
molecular formula: C17H12Br2O3
molecular weight: 424.08
cas number: 3562-84-3
definition:
  en: Benzbromarone, when dried, contains not less than 98.
appearance:
  en: Benzbromarone occurs as a white to light yel- low crystalline powder. It is very soluble in N,N-dimethylformamide, freely solu-ble in acetone, sparingly soluble in ethanol (99.5), and prac-tically insoluble in water. It dissolves in dilute sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Benzbromarone in 0.01 mol/L sodium hydroxide TS (1 in 100,000) as directed under Ultraviolet-visible Spec-trophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Benz-bromarone, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfate <1.14>—Dissolve 1.0 g of Benzbro-marone in 40 mL of acetone, and add 1 mL of dilute hydro-chloric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.40 mL of 0.005 mol/L sulfuric acid VS add 40 mL of acetone, 1 mL of dilute hydrochloric acid and water to make 50 mL (not more than 0.019z). Soluble halides—Dissolve 0.5 g of Benzbromarone in 40 mL of acetone, and add 6 mL of dilute nitric acid and water to make 50 mL. Proceed with this solution as directed under Chloride Limit Test <1.03>. Prepare the control solu-tion as follows: to 0.25 mL of 0.01 mol/L hydrochloric acid VS add 40 mL of acetone, 6 mL of dilute nitric acid and water to make 50 mL. Heavy metals <1.07>—Proceed with 2.0 g of Benzbro- marone according to Method 2, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 10 ppm). Iron <1.10>—Prepare the test solution with 1.0 g of Benzbromarone according to Method 3, and perform the test according to Method A. Prepare the control solution with 2.0 mL of Standard Iron Solution (not more than 20 ppm). Related substances—Dissolve 0.10 g of Benzbro-marone in 10 mL of acetone, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add ace-tone to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of cyclo-hexane, 4-methyl-2-pentanone, ethanol (99.5) and acetic acid (100) (100:20:2:1) to a distance of about 15 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the stan…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Benzbromarone, previously dried, dissolve in 30 mL of N,N-dimethylfor-mamide, and titrate <2.50> with 0.1 mol/L tetramethylam-monium hydroxide VS (indicator: 5 drops of thymol blue dimethylformamide TS). Perform a blank determination in ‌522‌ the same manner, and make any necessary correction. Each mL of 0.1 mol/L tetramethylammonium hydroxide VS ＝ 42.41 mg of C17H12Br2O3
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

benzethonium-chloride
type: ChemicalDrugMonograph
pref label:
  en: Benzethonium Chloride
  ja: ベンゼトニウム塩化物
monograph id: JP18-benzethonium-chloride
publisher: JP
status: Official
version: 18
molecular formula: C27H42ClNO2
molecular weight: 448.08
cas number: 121-54-0
definition:
  en: Benzethonium Chloride, when dried, contains not less than 97.
appearance:
  en: Benzethonium Chloride occurs as colorless or white crystals. It is odorless. It is very soluble in ethanol (95), freely soluble in water, and practically insoluble in diethyl ether. A solution of Benzethonium Chloride foams strongly when shaken.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.2 g of Benzethonium Chlo-ride in 1 mL of sulfuric acid, add 0.1 g of sodium nitrate, and heat for 5 minutes on a water bath. After cooling, add 10 mL of water and 0.5 g of zinc powder, heat for 5 minutes, cool, and filter: the filtrate responds to Qualitative Tests <1.09> for primary aromatic amines, developing a red color. To 2 mL of a solution of Benzethonium Chloride (1 in 1000) add a mixture of 0.2 mL of a solution of bromo-phenol blue (1 in 2000) and 0.5 mL of sodium hydroxide TS: a blue color develops. Add 4 mL of chloroform to this solu-tion, and shake vigorously: the blue color shifts to the chlo-roform layer. Collect the chloroform layer, and add drop-wise a solution of sodium lauryl sulfate (1 in 1000) with stirring: the chloroform layer turns colorless. Determine the absorption spectrum of a solution of Benzethonium Chloride in 0.1 mol/L hydrochloric acid TS (1 in 5000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. To 1 mL of a solution of Benzethonium Chloride (1 in 100) add 2 mL of ethanol (95), 0.5 mL of dilute nitric acid and 1 mL of silver nitrate TS: a white precipitate is pro-duced. This precipitate does not dissolve on addition of dilute nitric acid, but dissolves on addition of ammonia TS.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Ammonium—Dissolve 0.10 g of Benzethonium Chloride in 5 mL of water, and boil with 3 mL of sodium hy-droxide TS: the evolving gas dose not change moistened red litmus paper to blue. Loss on drying <2.41> Not more than 5.0z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Benzethonium Chloride, previously dried, dissolve in 75 mL of water, add diluted dilute hydrochloric acid (1 in 2) dropwise to adjust the pH to 2.6–3.4, then add 1 drop of methyl orange TS, and titrate <2.50> with 0.02 mol/L tetraphenylboron VS until the solution develops a red. Each mL of 0.02 mol/L sodium tetraphenylboron VS ＝ 8.962 mg of C27H42ClNO2
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

benzoic-acid
type: ChemicalDrugMonograph
pref label:
  en: Benzoic Acid
  ja: 安息香酸
monograph id: JP18-benzoic-acid
publisher: JP
status: Official
version: 18
molecular formula: C7H6O2
molecular weight: 122.12
definition:
  en: Benzoic acid [65-85-0] Benzoic Acid, when dried, contains not less than 99.
appearance:
  en: Benzoic Acid occurs as white, crystals or crys-talline powder. It is odorless, or has a faint, benzaldehyde-like odor. It is freely soluble in ethanol (95), in acetone and in diethyl ether, soluble in hot water, and slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Dissolve 1 g of Benzoic Acid in 8 mL of so-dium hydroxide TS, and add water to make 100 mL. This solution responds to Qualitative Tests <1.09> (2) for benzo-ate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Dissolve 1.0 g of Ben-zoic Acid in 25 mL of acetone, add 2 mL of dilute acetic acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of Standard Lead Solution add 2 mL of dilute acetic acid, 25 mL of acetone and water to make 50 mL (not more than 20 ppm). Chlorinated compounds—Take 0.5 g of Benzoic Acid and 0.7 g of calcium carbonate in a crucible, mix with a small amount of water, and dry. Ignite it at about 6009C, dissolve in 20 mL of dilute nitric acid, and filter. Wash the residue with 15 mL of water, combine the filtrate and the washing, add water to make 50 mL, and add 0.5 mL of silver nitrate TS: this solution has not more turbid than the follow-
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Benzoic Acid, pre-viously dried, dissolve in 25 mL of neutralized ethanol and 25 mL of water, and titrate <2.50> with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS). Each mL of 0.1 mol/L sodium hydroxide VS ＝ 12.21 mg of C H O 7 6 2 Description Benzoic Acid occurs as white, crystals or crys-talline powder. It is odorless, or has a faint, benzaldehyde-like odor. It is freely soluble in ethanol (95), in acetone and in diethyl ether, soluble in hot water, and slightly soluble in water. Identification Dissolve 1 g of Benzoic Acid in 8 mL of so-dium hydroxide TS, and add water to make 100 mL. This solution responds to Qualitative Tests <1.09> (2) for benzo-ate. Melting point <2.60> 121 – 1249C Purity (1) Heavy metals <1.07>—Dissolve 1.0 g of Ben-zoic Acid in 25 mL of acetone, add 2 mL of dilute acetic acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of Standard Lead Solution add 2 mL of dilute acetic acid, 25 mL of acetone and water to make 50 mL (not more than 20 ppm). Chlorinated compounds—Take 0.5 g of Benzoic Acid and 0.7 g of calcium carbonate in a crucible, mix with a small amount of water, and dry. Ignite it at about 6009C, dissolve in 20 mL of dilute nitric acid, and filter. Wash the residue with 15 mL of water, combine the filtrate and the washing, add water to make 50 mL, and add 0.5 mL of silver nitrate TS: this solution has not more turbid than the follow-
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

benzoinum
type: ChemicalDrugMonograph
pref label:
  en: Benzoinum
  ja: アンソッコウ
monograph id: JP18-benzoinum
publisher: JP
status: Official
version: 18
appearance:
  en: Benzoin occurs as grayish brown to dark red-brown blocks varying in size; the fractured surface exhibiting whitish to light yellow-red grains in the matrix; hard and brittle at ordinary temperature but softened by heat. Odor, characteristic and aromatic; taste, slightly pungent and acrid. ‌Identification (1) Heat a fragment of Benzoin in a test tube: it evolves an irritating vapor, and a crystalline subli-mate is produced. (2) Digest 0.5 g of Benzoin with 10 mL of diethyl ether, decant 1 mL of the diethyl ether into a porcelain dish, and add 2 to 3 drops of sulfuric acid: a deep red-brown to deep red-purple color develops.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Ethanol-insoluble substances—Boil gently 1.0 g of Benzoin with 30 mL of ethanol (95) for 15 minutes under a reflux condenser. After cooling, collect the insoluble sub-stances through a tared glass filter (G3), and wash with three 5-mL portions of ethanol (95). Dry the residue at 1059C for 4 hours: the mass of the residue does not exceed 0.30 g. Total ash <5.01> Not more than 2.0z. Acid-insoluble ash <5.01> Not more than 1.0z.
storage conditions:
  en: Containers—Well-closed contain-ers.

benzyl-alcohol
type: ChemicalDrugMonograph
pref label:
  en: Benzyl Alcohol
  ja: ベンジルアルコール
monograph id: JP18-benzyl-alcohol
publisher: JP
status: Official
version: 18
molecular formula: C7H8O
molecular weight: 108.14
definition:
  en: Benzyl alcohol [100-51-6] This monograph is harmonized with the European Phar-macopoeia and the U.S. Pharmacopeia. The parts of the text that are not harmonized are marked with symbols (◆ ◆). Information on the harmonization with the European Pharmacopoeia and the U.S. Pharmacopeia is available on the website of the Pharmaceuticals and Medical Devices Agency. Benzyl Alcohol contains not less than 98.
appearance:
  en: Benzyl Alcohol is a clear, colorless oily liq-uid. It is miscible with ethanol (95), with fatty oils and with essential oils. It is soluble in water. Specific gravity d 20: 1.043 – 1.049◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spec-trum of Benzyl Alcohol as directed in the liquid film method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.◆ D Refractive index <2.45> n20: 1.538 – 1.541
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: ◆(1) Clarity and color of solution—Dissolve 2.0 mL of Benzyl Alcohol in 60 mL of water: the solution is clear and colorless.◆ Acidity—To 10 mL of Benzyl Alcohol add 10 mL of ethanol (95) and 2 drops of phenolphthalein TS, and add dropwise 0.1 mol/L sodium hydroxide VS until the solution acquires a light red color: the amount of 0.1 mol/L sodium hydroxide VS used is not more than 1.0 mL. Benzaldehyde and other related substances—Use Benzyl Alcohol as the sample solution. Separately, dissolve exactly 0.100 g of ethylbenzene in Benzyl Alcohol to make exactly 10 mL. Pipet 2 mL of this solution, add Benzyl Alco-hol to make exactly 20 mL, and use this solution as the ethyl-benzene stock solution. Separately, dissolve exactly 2.000 g of dicyclohexyl in Benzyl Alcohol to make exactly 10 mL. Pipet 2 mL of this solution, add Benzyl Alcohol to make ex-actly 20 mL, and use this solution as the dicyclohexyl stock solution. Separately, weigh exactly 0.750 g of benzaldehyde and 0.500 g of cyclohexylmethanol, and add Benzyl Alcohol to make exactly 25 mL. Pipet 1 mL of this solution, add ex-actly 2 mL of ethylbenzene stock solution and exactly 3 mL of dicyclohexyl stock solution, then add Benzyl Alcohol to make exactly 20 mL, and use this solution as the standard solution (1). Perform the test with exactly 0.1 mL each of the sample solution and standard solution (1) as directed under Gas Chromatography <2.02> according to the following con-ditions, and when the peak having the retention time cor-responding to ethylbenzene and dicyclohexyl appears on the chromatogram obtained from the sample solution, correct the peak areas of ethylbenzene and dicyclohexyl from the standard solution (1) by deducting the relevant peak area from the sample solution, the peak area of benzaldehyde from the sample solution is not more than the difference be-tween the peak areas of benzaldehyde of the sample solution and the standard solution (1) (0.15z), and the peak area of cyclohexylmethanol from the sa…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.9 g of Benzyl Alcohol, add exactly 15 mL of a freshly prepared mixture of de-hydrated pyridine and acetic anhydride (7:1), and heat on a water bath under a reflux condenser for 30 minutes. Cool, add 25 mL of water, and titrate <2.50> the excess acetic acid with 1 mol/L sodium hydroxide VS (indicator: 2 drops of phenolphthalein TS). Perform a blank determination in the same manner. Each mL of 1 mol/L sodium hydroxide VS ＝ 108.1 mg of C7H8O
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.◆
type: PharmacopoeiaMonograph

benzyl-benzoate
type: ChemicalDrugMonograph
pref label:
  en: Benzyl Benzoate
  ja: 安息香酸ベンジル
monograph id: JP18-benzyl-benzoate
publisher: JP
status: Official
version: 18
molecular formula: C14H12O2
molecular weight: 212.24
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

benzylpenicillin-benzathine-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Benzylpenicillin Benzathine Hydrate
  ja: ベンジルペニシリンベンザチン水和物
monograph id: JP18-benzylpenicillin-benzathine-hydrate
publisher: JP
status: Official
version: 18
cas number: 41372-02-5
definition:
  en: Benzylpenicillin Benzathine Hydrate is the N,N?-dibenzylethylenediamine salt of a penicillin compound having antibacterial activity produced by the growth of Penicillium species. It contains not less than 1213 Units and not more than 1333 Units per mg, calculated on the anhydrous basis.
appearance:
  en: Benzyl Benzoate is a colorless, clear, viscous liquid. It has a faint, aromatic odor and a pungent, burning taste. It is miscible with ethanol (95) and with diethyl ether. It is practically insoluble in water. Congealing point: about 179C Specific gravity d 20: about 1.123 Boiling point: about 3239C
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Heat gently 1 mL of Benzyl Benzoate with 5 mL of sodium carbonate TS and 2 mL of potassium permanganate TS: the odor of benzaldehyde is perceptible. Warm the titrated mixture obtained in the Assay on a water bath to remove ethanol, and add 0.5 mL of iron (III) chloride TS: a light yellow-red precipitate is produced, which turns white on the addition of dilute hydrochloric acid. D Refractive index <2.45> n20: 1.568 – 1.570
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Acidity—Dissolve 5.0 mL of Benzyl Benzoate in 25 mL of neutralized ethanol, and add 0.50 mL of 0.1 mol/L sodium hydroxide VS: a red color develops. Residue on ignition <2.44> Not more than 0.05z (2 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 2 g of Benzyl Benzoate, add exactly 50 mL of 0.5 mol/L potassium hydroxide-ethanol VS, and boil gently for 1 hour under a reflux condenser with a carbon dioxide-absorbing tube (soda lime). Cool, and titrate <2.50> the excess potassium hydroxide with 0.5 mol/L Description Benzylpenicillin Benzathine Hydrate occurs as a white crystalline powder. It is slightly soluble in methanol and in ethanol (99.5), and practically insoluble in water. Identification (1) Determine the absorption spectrum of a solution of Benzylpenicillin Benzathine Hydrate in methanol (1 in 2000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Ben-zylpenicillin Benzathine Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋217 – ＋2339(0.1 g calcu-lated on the anhydrous basis, methanol, 20 mL, 100 mm). Purity (1) Heavy metals <1.07>—Proceed with 1.0 g of Benzylpenicillin Benzathine Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Benzylpenicillin Benzathine Hydrate according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 70 mg of Benzylpenicil-lin Benzathine Hydrate in 25 mL of methanol, add a solution prepared by dissolving 1.02 g of disodium hydrogen phos-phate and 6.80 g of potassium dihydrogen phosphate in water to make 1000 mL to make 50 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase A to make exactly 100 mL, and use t…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

bepotastine-besilate
type: ChemicalDrugMonograph
pref label:
  en: Bepotastine Besilate
  ja: ベポタスチンベシル酸塩
monograph id: JP18-bepotastine-besilate
publisher: JP
status: Official
version: 18
molecular formula: C21H25ClN2O3.C6H6O3S
molecular weight: 547.06
cas number: 190786-44-8
definition:
  en: Bepotastine Besilate contains not less than 99.
appearance:
  en: Bepotastine Besilate occurs as white to pale yellow-white, crystals or crystalline powder. It is very soluble in acetic acid (100), and sparingly soluble in water and in ethanol (99.5). The pH of a solution of 1 g of Bepotastine Besilate in 100 mL of water is about 3.8.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bepotastine Besilate (1 in 20,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bepotastine Besilate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Bepotastine Besilate as directed under Flame Coloration Test <1.04> (2): a green color ap-pears. Mix well 30 mg of Bepotastine Besilate with 0.1 g of sodium nitrate and 0.1 g of anhydrous sodium carbonate, and gradually ignite. After cooling, dissolve the residue in 2 mL of dilute hydrochloric acid and 10 mL of water, filter if necessary, and add barium chloride TS: a white precipitate is produced.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Bepotastine Besilate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 10 mg of Bepotastine Besilate in 25 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the area of the peak, having a relative retention time of about 2.5 to bepotastine, obtained from the sample solution is not larger than the peak area of bepotastine from the standard solu-tion, and the area of the peak other than bepotastine and the peak mentioned above from the sample solution is not larger than 1/10 times the peak area of bepotastine from the stand-ard solution. Furthermore, the total area of the peaks other than bepotastine from the sample solution is not larger than the peak area of bepotastine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 220 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 mm in particle diame-ter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 1.0 g of sodium 1-pentane sul-fonate in a mixture of 0.05 mol/L potassium dihydrogen phosphate TS (pH 3.0) and acetonitrile (7:3) to make 1000 mL. Flow rate: Adjust so that the retention time of bepotastine is about 6 minutes. Time span of measurement: About 5 times as long as the retention time of bepotastine, beginning after the peak of benzenesulfonic acid. System suitability— Test for require…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.8 g of Bepotastine Besi-late, dissolve in 60 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 54.71 mg of C21H25ClN2O3.C6H6O3S
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

berberine-chloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Berberine Chloride Hydrate
  ja: ベルベリン塩化物水和物
monograph id: JP18-berberine-chloride-hydrate
publisher: JP
status: Official
version: 18
definition:
  en: Berberine Chloride Hydrate contains not less than 95.
appearance:
  en: Berberine Chloride Hydrate occurs as yellow, crystals or crystalline powder. It is odorless or has a faint, characteristic odor. It has a very bitter taste. It is sparingly soluble in methanol, slightly soluble in ethanol (95), and very slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Berberine Chloride Hydrate (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, Amount (mg) of beraprost sodium (C24 ＝ MS × QT/QS × 1/500 H29 NaO5) and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Berberine Chloride RS prepared in the same manner as the sample solution: both MS: Amount (mg) of beraprost sodium for assay taken Internal standard solution—A mixture of water and a solu-tion of 4-isopropylphenol in methanol (1 in 250,000) (1:1). Operating conditions— Detector: A fluorophotometer (excitation wavelength: 285 nm, fluorescence wavelength: 614 nm). Column: A stainless steel column 6 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Ber-berine Chloride Hydrate as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Berberine Chloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolve 0.1 g of Berberine Chloride Hydrate in 20 ‌534 mL of water by warming, add 0.5 mL of nitric acid, cool, and filter after allowing to stand for 10 minutes. To 3 mL of the filtrate add 1 mL of silver nitrate TS, and collect the pro-duced precipitate: the precipitate does not dissolve in dilute nitric acid, but it dissolves in an excess amount of ammonia TS.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—Shake thoroughly 0.10 g of Berberine Chloride Hydrate with 30 mL of water, and filter. To the fil-trate add 2 drops of phenolphthalein TS and 0.10 mL of 0.1 mol/L sodium hydroxide VS: the yellow color changes to an orange to red color. Sulfate <1.14>—Shake 1.0 g of Berberine Chloride Hydrate with 48 mL of water and 2 mL of dilute hydrochlo-ric acid for 1 minute, and filter. Discard the first 5 mL of the filtrate, take the subsequent 25 mL of the filtrate, add water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS, 1 mL of dilute hydrochloric acid, 5 to 10 drops of bromophenol blue TS and water to make 50 mL (not more than 0.048z). Heavy metals <1.07>—Proceed with 1.0 g of Berber- ine Chloride Hydrate according to Method 2, and perform the test. Prepare the control solution with 3.0 mL of Stand-ard Lead Solution (not more than 30 ppm). Related substances—Dissolve 10 mg of Berberine Chloride Hydrate in 100 mL of the mobile phase, and use this solution as the sample solution. Pipet 4 mL of the sam-ple solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the total area of the peaks other than berberine ob-tained from the sample solution is not larger than the peak area of berberine from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, flow rate, and selection of column: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 2 times as long as the retention time of berberine, beginning after the solvent peak. Detection sensitivity: Adjust so that the peak height of berberine o…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 10 mg of Berberine Chloride Hydrate, dissolve in the mobile phase to make exactly 100 mL, and use this solution as the sample solution. Separately, weigh accurately about 10 mg of Berberine Chloride RS (separately, determine the water content <2.48> in the same manner as Berberine Chloride Hydrate), and dissolve in the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine the peak areas, AT and AS of berberine in each solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 345 nm). Column: A stainless steel column about 4 mm in inside diameter and about 25 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 3.4 g of monobasic potassium phosphate and 1.7 g of sodium lauryl sulfate in 1000 mL of a mixture of water and acetonitrile (1:1). Flow rate: Adjust so that the retention time of berberine is about 10 minutes. Selection of column: Dissolve each 1 mg of berberine chloride and palmatin chloride in the mobile phase to make 10 mL. Proceed with 10 mL of this solution under the above operating conditions, and calculate the resolution. Use a column giving elution of palmatin and berberine in this order with the resolution between these peaks being not less than 1.5. System repeatability: When the test is repeated 5 times with the standard solution under the above operating condi-tions, the relative standard deviation of the peak areas of berberine is not more than 1.5z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

berberine-tannate
type: ChemicalDrugMonograph
pref label:
  en: Berberine Tannate
  ja: タンニン酸ベルベリン
monograph id: JP18-berberine-tannate
publisher: JP
status: Official
version: 18
definition:
  en: Berberine Tannate is a compound of berberine and tannic acid. It contains not less than 27.
appearance:
  en: Berberine Tannate occurs as a yellow to light yellow-brown powder. It is odorless or has a faint, charac-teristic odor, and is tasteless. It is practically insoluble in water, in acetonitrile, in meth-anol and in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 0.1 g of Berberine Tannate add 10 mL of ethanol (95), and heat in a water bath for 3 minutes with shaking. Cool, filter, and to 5 mL of the filtrate add 1 drop of iron (III) chloride TS: a blue-green color is pro-duced, and on allowing to stand, a bluish black precipitate is formed. Dissolve 0.01 g of Berberine Tannate in 10 mL of methanol and 0.4 mL of 1 mol/L hydrochloric acid TS, and add water to make 200 mL. To 8 mL of the solution add water to make 25 mL. Determine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Ber-berine Tannate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com- Amount (mg) of berberine chloride (C ＝ MS × AT/AS 20H18ClNO4) pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. MS: Amount (mg) of Berberine Chloride RS taken, calcu-lated on the anhydrous basis
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—To 0.10 g of Berberine Tannate add ‌JP XVIII Official Monographs / Betahistine Mesilate 535 30 mL of water, and filter after shaking well. To the filtrate add 2 drops of phenolphthalein TS and 0.10 mL of 0.1 mol/L sodium hydroxide VS: the color of the solution changes from yellow to orange to red. Chloride <1.03>—Shake 1.0 g of Berberine Tannate with 38 mL of water and 12 mL of dilute nitric acid for 5 to make exactly 100 mL, and use this solution as the stand-ard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions. Determine the peak areas, AT and AS, of berberine in each solution. minutes, and filter. Discard the first 5 mL of the filtrate, to 25 mL of the subsequent filtrate add water to make 50 mL, and perform the test using this solution as the test solution. Amount (mg) of berberine (C ＝ MS × AT/AS × 0.950 20H19NO5) Prepare the control solution with 0.50 mL of 0.01 mol/L hy-drochloric acid VS by adding 6 mL of dilute nitric acid, 10 to 15 drops of bromophenol blue TS and water to make 50 mL (not more than 0.035z). Sulfate <1.14>—Shake 1.0 g of Berberine Tannate with 48 mL of water and 2 mL of dilute hydrochloric acid for 1 minute, and filter. Discard the first 5 mL of the filtrate, take the subsequent 25 mL of the filtrate, add water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS, 1 mL of dilute hydrochloric acid, 5 to 10 drops of bromophenol blue TS and water to make 50 mL (not more than 0.048z). Heavy metals <1.07>—Proceed with 1.0 g of Berber- ine Tannate according to Method 2, and perform the test. Prepare the control solution with 3.0 mL of Standard Lead Solution (not more than 30 ppm). Related substances—Dissolve 10 mg of Berberine Tannate in 100 mL of the mobile phase, and use this solution as the sample solut…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 30 mg of Berberine Tan-nate, dissolve in the mobile phase to make exactly 100 mL, and use this solution as the sample solution. Separately, weigh accurately about 10 mg of Berberine Chloride RS (separately, determine the water <2.48> in the same manner as Berberine Chloride Hydrate), dissolve in the mobile phase MS: Amount (mg) of Berberine Chloride RS taken, calcu-lated on the anhydrous basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 345 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 3.4 g of potassium dihydrogen phosphate and 1.7 g of sodium lauryl sulfate in 1000 mL of a mixture of water and acetonitrile (1:1). Flow rate: Adjust so that the retention time of berberine is about 10 minutes. System suitability— System performance: Dissolve 1 mg each of berberine chloride and palmatin chloride in the mobile phase to make 10 mL. When the procedure is run with 10 mL of this solu-tion under the above operating conditions, palmatin and ber-berine are eluted in this order with the resolution between these peaks being not less than 1.5. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of berberine is not more than 1.5z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.

betahistine-mesilate
type: ChemicalDrugMonograph
pref label:
  en: Betahistine Mesilate
  ja: ベタヒスチンメシル酸塩
monograph id: JP18-betahistine-mesilate
publisher: JP
status: Official
version: 18
molecular formula: C8H12N2.2CH4O3S
molecular weight: 328.41
definition:
  en: Betahistine Mesilate, when dried, contains not less than 98.
appearance:
  en: Betahistine Mesilate occurs as white, crystals or crystalline powder. It is very soluble in water, freely soluble in acetic acid (100), and sparingly soluble in ethanol (99.5). It dissolves in dilute hydrochloric acid. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Betahistine Mesilate in 0.1 mol/L hydrochloric acid (1 in 50,000) as directed under Ultraviolet-visible Spec-trophotometry <2.24>, and compare the spectrum with the ‌536 Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Beta-histine Mesilate, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. A 30 mg portion of Betahistine Mesilate responds to Qualitative Tests <1.09> (2) for mesilate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Betahistine Mesilate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 50 mg of Betahistine Mesilate in 10 mL of a mixture of water and acetonitrile (63:37), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mixture of water and acetonitrile (63:37) to make exactly 100 mL, and use this so-lution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as Loss on drying <2.41> Not more than 1.0z (1 g, in vacu-um, phosphorus (V) oxide, 709C, 24 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Betahistine Mesi-late, previously dried, dissolve in 1 mL of acetic acid (100), add 50 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 16.42 mg of C8H12N2.2CH4O3S
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

betamethasone-dipropionate
type: ChemicalDrugMonograph
pref label:
  en: Betamethasone Dipropionate
  ja: ベタメタゾンジプロピオン酸エステル
monograph id: JP18-betamethasone-dipropionate
publisher: JP
status: Official
version: 18
molecular formula: C28H37FO7
molecular weight: 504.59
cas number: 5593-20-4
definition:
  en: Betamethasone Dipropionate, when dried, contains not less than 97.
appearance:
  en: Betamethasone Dipropionate occurs as a white to pale yellow-white crystalline powder. It is odorless. It is freely soluble in acetone and in chloroform, soluble in the sample solution, add chloroform to make exactly 100 mL, and use this solution as the standard solution. Perform the test as directed under Thin-layer Chromatography <2.03> with these solutions. Spot 20 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent ‌JP XVIII Official Monographs / Betamethasone Sodium Phosphate 541 indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform and acetone (7:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultra-violet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 1.0z (0.5 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.2z (0.5 g, platinum crucible).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of a solution of Betametha-sone Dipropionate in methanol (1 in 10,000) add 4 mL of isoniazid TS, and heat on a water bath for 2 minutes: a yellow color develops. Proceed with 0.01 g of Betamethasone Dipropionate as directed under Oxygen Flask Combustion Method <1.06>, using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as the absorbing liquid: the test solu-tion so obtained responds to the Qualitative Tests <1.09> for fluoride. Determine the absorption spectrum of a solution of Betamethasone Dipropionate in methanol (3 in 200,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Beta-methasone Dipropionate, previously dried, as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. D Optical rotation <2.49> [a]25: ＋84 – ＋899(after drying, 50 mg, ethanol (99.5), 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Fluoride—To 0.10 g of Betamethasone Dipro-pionate add 10.0 mL of diluted 0.01 mol/L sodium hydrox-ide TS (1 in 20), shake for 10 minutes, and filter through a membrane filter (0.4-mm pore size). Place 5.0 mL of the fil-trate in a 20-mL volumetric flask, and add 10 mL of a mix-ture of alizarin complexone TS, acetic acid-potassium ace-tate buffer solution (pH 4.3) and cerium (III) nitrate TS (1:1:1), add water to make 20 mL, allow to stand for 1 hour, and use this solution as the sample solution. Separately, place 1.0 mL of Standard Fluorine Solution in a 20-mL volu-metric flask, add 5.0 mL of diluted 0.01 mol/L sodium hy-droxide TS (1 in 20), then 10 mL of a mixture of alizarin complexone TS, acetic acid-potassium acetate buffer solu-tion (pH 4.3) and cerium (III) nitrate TS (1:1:1), proceed in the same manner as the preparation of the sample solution, and use this solution as the standard solution. Place 5.0 mL of diluted 0.01 mol/L sodium hydroxide TS (1 in 20) in a 20-mL volumetric flask, and proceed in the same manner as the preparation of the sample solution. Using this solution as the blank, determine the absorbances of the sample solution and standard solution at 600 nm as directed under Ultravio-let-visible Spectrophotometry <2.24>: the absorbance of the sample solution is not more than that of the standard solu-tion (not more than 0.012z). Heavy metals <1.07>—Proceed with 1.0 g of Beta-methasone Dipropionate according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 10 betamethasone dipropionate (C28 H37 FO7), and not less mg of Betamethasone Dipropionate in 10 mL of chloroform, and use this solution as the sample solution. Pipet 3 mL of than 3.4z and not more than 4.1z of fluorine (F:19.00). Description Betamethasone Dipropionate occurs as a white to pale yellow-white c…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Betamethasone dipropionate—Weigh accu-rately about 15 mg of Betamethasone Dipropionate, previ-ously dried, and dissolve in methanol to make exactly 100 mL. Pipet 5 mL of this solution, and dilute with methanol to exactly 50 mL. Determine the absorbance A of this solution at the wavelength of maximum absorption at about 239 nm as directed under Ultraviolet-visible Spectrophotometry <2.24>. Amount (mg) of betamethasone dipropionate (C28H37FO7) ＝ A/312 × 10,000 (2) Fluorine—Weigh accurately about 10 mg of Beta-methasone Dipropionate, previously dried, and proceed as directed in the procedure of determination for fluorine under Oxygen Flask Combustion Method <1.06>, using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as the absorbing liquid.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

betamethasone-valerate
type: ChemicalDrugMonograph
pref label:
  en: Betamethasone Valerate
  ja: ベタメタゾン吉草酸エステル
monograph id: JP18-betamethasone-valerate
publisher: JP
status: Official
version: 18
molecular formula: C27H37FO6
molecular weight: 476.58
cas number: 2152-44-5
definition:
  en: Betamethasone Valerate, when dried, contains not less than 97.
appearance:
  en: Betamethasone Valerate occurs as a white crys-talline powder. It is odorless. It is freely soluble in chloroform, soluble in ethanol (95), sparingly soluble in methanol, slightly soluble in diethyl ether, and practically insoluble in water. Melting point: about 1909C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Proceed with 0.01 g of Betamethasone Valerate as directed under Oxygen Flask Combustion Method <1.06>, using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as the absorbing liquid: the test solution so obtained responds to Qualitative Tests <1.09> for fluoride. (2) Determine the infrared absorption spectrum of Beta-methasone Valerate, previously dried, as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of dried Betamethasone Valerate RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋77 – ＋839(after drying, 0.1 g, methanol, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Related substances—Conduct this procedure with-out exposure to daylight. Dissolve 0.02 g of Betamethasone Valerate in 5 mL of a mixture of chloroform and methanol (9:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of chloroform and methanol (9:1) to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. De-velop the plate with a mixture of chloroform and methanol (9:1) to a distance of about 12 cm, and air-dry the plate. Spray evenly alkaline blue tetrazolium TS on the plate: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the stand-ard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.2z (0.5 g, platinum crucible).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Dissolve about 10 mg each of Betamethasone Valer-ate and Betamethasone Valerate RS, previously dried and JP XVIII Official Monographs / Betamethasone Valerate and Gentamicin Sulfate Cream 543 ‌accurately weighed, in methanol to make exactly 100 mL. Pipet 10 mL each of these solutions, add 10 mL each of the internal standard solution, and use these solutions as the sample solution and the standard solution, respectively. Per-form the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of betamethasone valerate to that of the internal standard. these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 5 mL each of the sample solution and stand-ard solution on a plate of silica gel for thin-layer chromatog-raphy, develop the plate with ethyl acetate to a distance of about 10 cm, and air-dry the plate. Spray evenly alkaline blue tetrazolium TS on the plate, and heat the plate at 1009C: the principal spot obtained from the sample solution and the spot from the standard solution are purple in color, and their Rf values are the same. Amount (mg) of betamethasone valerate (C ＝ MS × QT/QS 27H37FO6) (2) To a quantity of Betamethasone Valerate and Gen-tamicin Sulfate Cream, equivalent to about 2 mg (potency) of Gentamicin Sulfate, add 20 mL of ethyl acetate and 10 MS: Amount (mg) of Betamethasone Valerate RS taken Internal standard solution—A solution of isoamyl benzoate in methanol (1 in 1000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.0 mm in inside diame-ter and 20 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (7 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of methanol and water (7:3). Flow rate: Adjust so that the retention t…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

betamethasone
type: ChemicalDrugMonograph
pref label:
  en: Betamethasone
  ja: ベタメタゾン
monograph id: JP18-betamethasone
publisher: JP
status: Official
version: 18
molecular formula: C22H29FO5
molecular weight: 392.46
cas number: 378-44-9
definition:
  en: Betamethasone, when dried, contains not less than 96.
appearance:
  en: Betamethasone occurs as a white to pale yel-low-white crystalline powder. It is sparingly soluble in methanol, in ethanol (95) and in acetone, and practically insoluble in water. Melting point: about 2409C (with decomposition). It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Proceed with 10 mg of Betamethasone as directed under Oxygen Flask Combustion Method <1.06>, using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as the absorbing liquid: the test solu-tion so obtained responds to Qualitative Tests <1.09> for fluoride. Dissolve 1.0 mg of Betamethasone in 10 mL of ethanol (95). Mix 2.0 mL of the solution with 10 mL of phenylhydrazinium hydrochloride TS, heat in a water bath at 609C for 20 minutes, and cool the solution. Determine the absorption spectrum of the solution as directed under Ultra-violet-visible Spectrophotometry <2.24>, using as the blank the solution prepared with 2.0 mL of ethanol (95) in the same manner as the former solution, and compare the spec-trum with the Reference Spectrum or the spectrum of a solu-tion of Betamethasone RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Beta-methasone, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum or the spectrum of previously dried Betamethasone RS: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, dissolve Betamethasone and Betamethasone RS in acetone, respectively, then evaporate the acetone to dryness, and repeat the test on the residues. D Optical rotation <2.49> [a]20: ＋118 – ＋1269(after drying, 0.1 g, methanol, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 0.5 g of Betamethasone according to Method 2, and perform the test. Prepare the control solution with 1.5 mL of Standard Lead Solution (not more than 30 ppm). (2) Related substances—Dissolve 10 mg of Betametha-sone in 5 mL of a mixture of chloroform and methanol (9:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of chloroform and meth-anol (9:1) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, diethyl ether, methanol and water (385:75:40:6) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (0.5 g, in vacu-um, phosphorus (V) oxide, 4 hours). Residue on ignition <2.44> Not more than 0.5z (0.1 g, platinum crucible).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Dissolve about 20 mg each of Betamethasone and Betamethasone RS, previously dried and accurately weighed, in methanol to make exactly 50 mL. Pipet 5 mL each of these solutions, add exactly 5 mL each of the internal stand-ard solution, then add methanol to make 50 mL, and use these solutions as the sample solution and standard solution, respectively. Perform the test with 10 mL each of these solu-tions as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and calculate the ratios, QT and QS, of the peak area of betamethasone to that of the internal standard. Amount (mg) of betamethasone (C22H29FO5) ＝ MS × QT/QS MS: Amount (mg) of Betamethasone RS taken Internal standard solution—A solution of butyl parahy-droxybenzoate in methanol (1 in 1750). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 240 nm). Column: A stainless steel column about 4.0 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diame-ter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of water and acetonitrile (3:2). Flow rate: Adjust so that the retention time of betametha- sone is about 4 minutes. System suitability— System performance: When proceed the test with 10 mL of the standard solution under the above operating conditions, betamethasone and the internal standard are eluted in this order with the resolution between these peaks being not less than 10. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratio of the peak area of betamethasone to that of the internal stand-ard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

betamipron
type: ChemicalDrugMonograph
pref label:
  en: Betamipron
  ja: ベタミプロン
monograph id: JP18-betamipron
publisher: JP
status: Official
version: 18
molecular formula: C10H11NO3
molecular weight: 193.2
definition:
  en: Betamipron contains not less than 99.
appearance:
  en: Betamipron occurs as white, crystals or crys-talline powder. It is freely soluble in methanol, soluble in ethanol (99.5), and slightly soluble in water. It dissolves in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Betamipron in ethanol (99.5) (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Beta-mipron as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. pH <2.54> Dissolve 0.25 g of Betamipron in 100 mL of water by warming, and cool: the pH of this solution is be-tween 3.0 and 3.4.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Betamipron in 10 mL of sodium hydroxide TS: the solu-tion is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Beta- mipron according to Method 4, and perform the test. Pre-pare the control solution with 1.0 mL of Standard Lead So-lution (not more than 10 ppm). b-Alanine—Dissolve 0.25 g of Betamipron in 10 mL of methanol, and use this solution as the sample solution. Separately, dissolve 50 mg of b-alanine in methanol to make exactly 100 mL. Pipet 1 mL of this solution, add methanol to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography, develop the plate with a mixture of methanol, ethyl acetate, ammonia solution (28) and water (200:200:63:37) to a distance of about 10 cm, and air-dry the plate. Spray evenly ninhydrin-butanol TS on the plate, and heat the plate at 1059C for 5 minutes: the spot ob-tained from the sample solution corresponding to the spot ‌546 from the standard solution is not more intense than the spot from the standard solution. Related substances—Dissolve 20 mg of Betamipron in 100 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine each peak area by the au-tomatic integration method: the area of the peak other than betamipron from the sample solution is not larger than 2/5 times the peak area of betamipron from the standard solu-tion, and the total area of the peaks other than betamipron from the sample solution is not larger than the peak…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of Betamipron, dis-solve in 25 mL of ethanol (99.5), add 25 mL of water, and titrate <2.50> with 0.1 mol/L sodium hydroxide VS (poten-tiometric titration). Perform the blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 19.32 mg of C10H11NO3
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

betaxolol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Betaxolol Hydrochloride
  ja: ベタキソロール塩酸塩
monograph id: JP18-betaxolol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C18H29NO3.HCl
molecular weight: 343.89
definition:
  en: Betaxolol Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Betaxolol Hydrochloride occurs as white, crys-tals or crystalline powder. It is very soluble in water, and freely soluble in methanol, in ethanol (99.5) and in acetic acid (100). Dissolve 1.0 g of Betaxolol Hydrochloride in 50 mL of water: the pH of the solution is between 4.5 and 6.5. A solution of Betaxolol Hydrochloride (1 in 100) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Betaxolol Hydrochloride in ethanol (99.5) (1 in 10,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Be-taxolol Hydrochloride as directed in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Betaxolol Hydrochloride (1 in 10) re-sponds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Betaxolol Hydrochloride in 10 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g of Betax- olol Hydrochloride according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 2.0 g of Betaxolol Hydrochloride according to Method 3, and per-form the test (not more than 1 ppm). Related substance I—Dissolve 0.10 g of Betaxolol Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 3 mL of the sample solution, and add methanol to make exactly 50 mL. Pipet 1 mL of this solution, add methanol to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatogra-phy. Develop the plate with a mixture of ethyl acetate, water and acetic acid (100) (10:3:3) to a distance of about 10 cm, and air-dry the plate. Allow the plate to stand in iodine vapor for 1 hour: the number of the spots other than the principal spot obtained from the sample solution is not more ‌JP XVIII Official Monographs / Bethanechol Chloride 547 than 3, and they are not more intense than the spot from the standard solution. Related substance II—Dissolve 0.10 g of Betaxolol Hydrochloride in 50 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the area of the peak other than betaxol…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Betaxolol Hydro-chloride, previously dried, dissolve in 30 mL of acetic acid (100), add 30 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 34.39 mg of C18H29NO3.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bethanechol-chloride
type: ChemicalDrugMonograph
pref label:
  en: Bethanechol Chloride
  ja: ベタネコール塩化物
monograph id: JP18-bethanechol-chloride
publisher: JP
status: Official
version: 18
molecular formula: C7H17ClN2O2
molecular weight: 196.68
definition:
  en: Bethanechol Chloride, when dried, contains not less than 98.
appearance:
  en: Bethanechol Chloride occurs as colorless or white crystals or a white, crystalline powder. It is very soluble in water, freely soluble in acetic acid (100), and sparingly soluble in ethanol (99.5). It is hygroscopic. A solution of Bethanechol Chloride (1 in 10) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2 mL of a solution of Bethanechol Chloride (1 in 40) add 0.1 mL of a solution of cobalt (II) chloride hexahydrate (1 in 100), then add 0.1 mL of potas-sium hexacyanoferrate (II) TS: A green color is produced, and almost entirely fades within 10 minutes. To 1 mL of a solution of Bethanechol Chloride (1 in 100) add 0.1 mL of iodine TS: a brown precipitate is pro-duced, and the solution shows a greenish brown color. Determine the infrared absorption spectrum of Bethanechol Chloride as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare the spec-trum with the Reference Spectrum: both spectra exhibit simi-lar intensities of absorption at the same wave numbers. A solution of Bethanechol Chloride (1 in 100) re-sponds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Bethanechol Chloride according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 1.0 g of Bethanechol Chloride in 2.5 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 1 mL each of the sample solution and standard solution on a plate of cellulose for thin-layer chromatography. Develop the plate with a mixture of a solution of ammonium acetate (1 in 100), acetone, 1-butanol and formic acid (20:20:20:1) to a distance of about 10 cm, and dry the plate at 1059C for 15 minutes. Spray evenly hydrogen hexachloroplatinate (IV)-potassium iodide TS on the plate, and allow to stand for 30 minutes: the spot other than the principal spot obtained from the sample solution is not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 1.0z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g). ‌548
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Bethanechol Chlo-ride, previously dried, dissolve in 2 mL of acetic acid (100), add 40 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 19.67 mg of C7H17ClN2O2
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bezafibrate
type: ChemicalDrugMonograph
pref label:
  en: Bezafibrate
  ja: ベザフィブラート
monograph id: JP18-bezafibrate
publisher: JP
status: Official
version: 18
molecular formula: C19H20ClNO4
molecular weight: 361.82
cas number: 41859-67-0
definition:
  en: Bezafibrate, when dried, contains not less than 98.
appearance:
  en: Bezafibrate occurs as a white crystalline pow-der. It is freely soluble in N,N-dimethylformamide, soluble in methanol, slightly soluble in ethanol (99.5), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bezafibrate in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bezafibrate, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Bezafibrate as directed under Flame Coloration Test <1.04> (2): a green color appears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 3.0 g of Bezafibrate in 15 mL of N,N-dimethylformamide, add water to make 60 mL, shake well, allow to stand for more than 12 hours, and filter. To 40 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution as follows: To 0.70 mL of 0.01 mol/L hydrochloric acid VS add 10 mL of N,N-dimethylformamide, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.012z). Heavy metals <1.07>—Proceed with 2.0 g of Bezafibrate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 0.10 g of Bezafibrate in 35 mL of methanol, add diluted 0.5 mol/L ammonium ace-tate TS (1 in 50) to make 50 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add 70 mL of methanol and diluted 0.5 mol/L ammonium acetate TS (1 in 50) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine each peak area by the au-tomatic integration method: the areas of the peaks having the relative retention times of about 0.65 and 1.86 to bezafibrate obtained from the sample solution are not larger than 1/2 times the peak area of bezafibrate from the stand-ard solution, the area of the peaks other bezafibrate and the peaks mentioned above from the sample solution is not larger than 1/5 times the peak area of bezafibrate from the standard solution, and the total area of the peaks other than the peak of bezafibrate from the sample solution is not larger than 3/4 times the peak area of bezafibrate from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 230 nm). Column: A stainless…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.7 g of Bezafibrate, previ-ously dried, dissolve in 50 mL of ethanol (99.5), and titrate <2.50> with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of phenolphthalein TS). Perform a blank determina-tion in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 36.18 mg of C19H20ClNO4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bezoar-bovis
type: ChemicalDrugMonograph
pref label:
  en: Bezoar Bovis
  ja: ゴオウ
monograph id: JP18-bezoar-bovis
publisher: JP
status: Official
version: 18
appearance:
  en: Spherical or massive stone, 1 – 4 cm in diame-ter; externally yellow-brown to red-brown; light, fragile and easily broken. Fractured surface shows yellow-brown to red-brown annular rings, often containing white granular sub-stances or thin layers in these annular rings. Odor, slight; taste, slightly bitter, followed by slight sweet-ness.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 25 mg of pulverized Oriental Bezoar add 10 mL of methanol, shake for 5 minutes, and centrifuge. Take the supernatant liquid, evaporate the solvent under low pressure (in vacuo), dissolve the residue in 0.5 mL of metha-nol, and use this solution as the sample solution. Separately, dissolve 5 mg each of cholic acid for thin-layer chromatogra-phy and deoxycholic acid for thin-layer chromatography in 5 mL of methanol, respectively, and use these solutions as the standard solution (1) and the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solu-tion, standard solutions (1) and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, formic acid and methanol (30:1:1) to a dis-tance of about 7 cm, and air-dry the plate. Spray evenly vanillin-sulfuric acid-ethanol TS for spraying on the plate, and heat the plate at 1059C for 10 minutes: two of the sever-al spots obtained from the sample solution have the same color tone and Rf value with each spot from the standard so-lutions (1) and (2).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Synthetic dye—To 2 mg of pulverized Oriental Bezoar add 1 mL dilute hydrochloric acid: no violet color de-velops. Starch—To 5 mg of pulverized Oriental Bezoar add 2 mL of water, and heat on a water bath for 5 minutes. Cool and add 2 to 3 drops of iodine TS: no blue-purple color de-velops. Sucrose—To 0.02 g of pulverized Oriental Bezoar add 10 mL of water, shake for 15 minutes, and filter. To 1 mL of the filtrate add 2 mL of anthrone TS, and shake: no deep blue-green to dark green color develops. Total ash <5.01> Not more than 10.0z.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Conduct this procedure without exposure to light us-ing light-resistant vessels. The following sample solution and standard solution should be prepared before use. Weigh ac-curately about 10 mg of pulverized Oriental Bezoar, add 10 mL of a mixture of dimethyl sulfoxide and acetic acid (100) (9:1), warm at 609C for 20 minutes, and add a mixture of dimethyl sulfoxide and acetic acid (100) (9:1) to make exactly 50 mL. Pipet 5 mL of this solution, add the mobile phase to make exactly 50 mL, ˆlter through a membrane ˆlter, and use the ˆltrate as the sample solution. Separately, weigh ac-curately about 10 mg of bilirubin for assay, add about 350 mg of L-ascorbic acid, and dissolve in a mixture of dimethyl sulfoxide and acetic acid (100) (9:1) to make exactly 100 mL. Pipet 5 mL of this solution, add the mobile phase to make exactly 50 mL, and use this solution as the standard solution. ‌JP XVIII Crude Drugs and Related Drugs / Otsujito Extract 2087 Perform the test with exactly 10 mL each of the sample solu-tion and standard solution as directed under Liquid Chro-matography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of bilirubin in each solution. Amount (mg) of bilirubin ＝ MS × AT/AS × 1/2 MS: Amount (mg) of bilirubin for assay taken Operating conditions— Detector: A visible absorption photometer (wavelength: 450 nm). Column: A stainless steel column 4.6 mm in inside di-ameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle di-ameter). Column temperature: A constant temperature of about 309C. Mobile phase: A mixture of acetonitrile and diluted acetic acid (100) (1 in 100) (19:1). Flow rate: Adjust so that the retention time of bilirubin is about 10 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of bilir…
storage conditions:
  en: Containers—Well-closed contain-ers.

bicalutamide
type: ChemicalDrugMonograph
pref label:
  en: Bicalutamide
  ja: ビカルタミド
monograph id: JP18-bicalutamide
publisher: JP
status: Official
version: 18
molecular formula: C18H14F4N2O4S
molecular weight: 430.37
definition:
  en: Bicalutamide contains not less than 98.
appearance:
  en: Bicalutamide occurs as a white, powder or crystalline powder. It is freely soluble in acetone, sparingly soluble in metha-nol, slightly soluble in ethanol (99.5), and practically insolu- ble in water. A solution of Bicalutamide in acetone (1 in 100) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bicalutamide in methanol (1 in 100,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Bicalutamide RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Bicalutamide as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Bicalutamide RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Alterna-tively, perform the test by the ATR method, and compare the spectrum with the spectrum of Bicalutamide RS: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, recrystallize Bicalutamide and Bicalutamide RS with acetone, respectively, filter and dry the crystals, and perform the test by the potassium bromide disk method or the ATR method in the same manner.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Bicalutamide according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 25 mg of Bicalutamide in 25 mL of a mixture of water, acetonitrile and phosphoric acid (1000:1000:1), and use this solution as the sample solu-tion. Pipet 1 mL of the sample solution, and add a mixture of water, acetonitrile and phosphoric acid (1000:1000:1) to make exactly 100 mL. Pipet 10 mL of this solution, add a mixture of water, acetonitrile and phosphoric acid (1000:1000:1) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method: the peak areas of related sub-stance M, having the relative retention time of about 0.26 to bicalutamide, related substance N, having the relative reten-tion time of about 0.34, related substance L, having the rela-tive retention time of about 1.03 and related substance K, having the relative retention time of about 1.13, obtained from the sample solution, are not larger than the peak area of bicalutamide from the standard solution, and the area of the peak other than bicalutamide and the peaks mentioned above from the sample solution is not larger than the peak area of bicalutamide from the standard solution. Further-more, the total area of the peaks other than bicalutamide from the sample solution is not larger than 5 times the peak area of bicalutamide from the standard solution. For the areas of the peaks, related substance G, having the relative retention times of about 0.21 and about 0.25, related sub-stance I, having the relative retention time of about 0.23, related substance M, related substance N, related substance O, having the relative retention time of…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately, and powder not less than 20 more than 102.0z of bicalutamide (C calculated on the dried basis. 18H14F4N2O4S), Bezafibrate Extended-release Tablets. Weigh accurately a portion of the powder, equivalent to about 20 mg of bezafibrate (C19H20ClNO4), add 60 mL of methanol and exactly 10 mL of the internal standard solution, and shake Description Bicalutamide occurs as a white, powder or crystalline powder. It is freely soluble in acetone, sparingly soluble in metha-nol, slightly soluble in ethanol (99.5), and practically insolu- ble in water. A solution of Bicalutamide in acetone (1 in 100) shows no optical rotation. Melting point <2.60> 192 – 1979C Bicalutamide shows crystal polymorphism. Identification (1) Determine the absorption spectrum of a solution of Bicalutamide in methanol (1 in 100,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Bicalutamide RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Bicalutamide as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Bicalutamide RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Alterna-tively, perform the test by the ATR method, and compare the spectrum with the spectrum of Bicalutamide RS: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, recrystallize Bicalutamide and Bicalutamide RS with acetone, respectively, filter and dry the crystals, and perform the test by the potassium bromide disk method or the ATR method in the same manner. Purity (1) Heavy metals <1.07>—Proceed with 2.0 g of Bicalutamide according to Method 2, and perform the test. Pr…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

bifonazole
type: ChemicalDrugMonograph
pref label:
  en: Bifonazole
  ja: ビホナゾール
monograph id: JP18-bifonazole
publisher: JP
status: Official
version: 18
molecular formula: C22H18N2
molecular weight: 310.39
definition:
  en: Bifonazole, when dried, contains not less than thin-layer chromatography.
appearance:
  en: Bifonazole occurs as a white to pale yellow powder. It is odorless and tasteless. It is freely soluble in dichloromethane, soluble in metha-nol, sparingly soluble in ethanol (95), slightly soluble in diethyl ether, and practically insoluble in water. A solution of Bifonazole in methanol (1 in 100) does not show optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bifonazole in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Bi-fonazole, previously dried, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—To 2.0 g of Bifonazole add 40 mL of water, warm for 5 minutes, and after cooling, filter. To 10 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solu-tion as the test solution. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—To 10 mL of the filtrate obtained in add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solu-tion. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (0.048z). Heavy metals <1.07>—Proceed with 2.0 g of Bifona- zole according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 0.10 g of Bifonazole in 10 mL of methanol, and use this solution as the sample solution. Pipet 3 mL of the sample solution, and add methanol to make exactly 100 mL. Pipet 25 mL and 5 mL of this solution, add methanol to make exactly 50 mL each, and use these solutions as the standard solutions (1) and (2), respectively. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solutions (1) and (2) on a plate of silica gel with fluorescent indicator for solution of methyl yellow in dichloromethane (1 in 500) as indicator, and titrate <2.50>, while shaking vigorously, with 0.01 mol/L sodium lauryl sulfate VS by a buret with 0.02-mL minimum graduation. The end point is reached when the color of the dichloromethane layer changes from yellow to orange-red after dropwise addition of 0.01 mol/L sodium lauryl sulfate VS, strong shaking, and standing for a while. Each mL of 0.01 mol/L sodium lauryl sulfate VS ＝ 3.104 mg of C22H18N2
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of Bifonazole, previ-ously dried, and dissolve in dichloromethane to make exactly 50 mL. Pipet 5 mL of this solution in a glass-stoppered coni- 98.5z of bifonazole (C 22H18 N2). cal flask, add 10 mL of water, 5 mL of dilute sulfuric acid and 25 mL of dichloromethane, and add 2 to 3 drops of a Description Bifonazole occurs as a white to pale yellow powder. It is odorless and tasteless. It is freely soluble in dichloromethane, soluble in metha-nol, sparingly soluble in ethanol (95), slightly soluble in diethyl ether, and practically insoluble in water. A solution of Bifonazole in methanol (1 in 100) does not show optical rotation. Identification (1) Determine the absorption spectrum of a solution of Bifonazole in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Bi-fonazole, previously dried, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Melting point <2.60> 147 – 1519C Purity (1) Chloride <1.03>—To 2.0 g of Bifonazole add 40 mL of water, warm for 5 minutes, and after cooling, filter. To 10 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solu-tion as the test solution. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—To 10 mL of the filtrate obtained in add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solu-tion. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (0.048z). Heavy metals <1.07>—Proceed with 2.0 g of Bifona- zole according to Me…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

biperiden-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Biperiden Hydrochloride
  ja: ビペリデン塩酸塩
monograph id: JP18-biperiden-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C21H29NO.HCl
molecular weight: 347.92
cas number: 1235-82-1
definition:
  en: Biperiden Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Biperiden Hydrochloride occurs as a white to brownish yellow-white crystalline powder. It is freely soluble in formic acid, slightly soluble in water, in methanol and in ethanol (95), and practically insoluble in diethyl ether. Melting point: about 2709C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.02 g of Biperiden Hydro-chloride in 5 mL of phosphoric acid: a green color develops. Dissolve 0.01 g of Biperiden Hydrochloride in 5 mL of water by heating, cool, and add 5 to 6 drops of bromine TS: a yellow precipitate is formed. Determine the absorption spectrum of a solution of Biperiden Hydrochloride (1 in 2000) as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Biperiden Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. Dissolve 0.02 g of Biperiden Hydrochloride in 10 mL of water by heating, and cool: the solution responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity or alkalinity—To 1.0 g of Biperiden Hydrochloride add 50 mL of water, shake vigorously, filter, and to 20 mL of the filtrate add 1 drop of methyl red TS: no red to yellow color develops. Heavy metals <1.07>—Proceed with 1.0 g of Biperiden Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Biperiden Hydrochloride according to Method 3, and per-form the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of Biperiden Hy-drochloride in 20 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 50 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform, methanol and am-monia solution (28) (80:15:2) to a distance of about 15 cm, and air-dry the plate. Spray evenly Dragendorff's TS for spraying on the plate: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Biperiden Hydro-chloride, previously dried, dissolve in 5 mL of formic acid, add 60 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 34.79 mg of C21H29NO.HCl
storage conditions:
  en: Containers—Well-closed contain-
type: PharmacopoeiaMonograph

bisacodyl-suppositories
type: ChemicalDrugMonograph
pref label:
  en: Bisacodyl Suppositories
  ja: ビサコジル坐剤
monograph id: JP18-bisacodyl-suppositories
publisher: JP
status: Official
version: 18
definition:
  en: Bisacodyl Suppositories contain not less than 90.0z and not more than 110.0z of the labeled amount of bisacodyl (C22H19NO4: 361.39). Method of preparation Prepare as directed under Supposi-tories, with Bisacodyl. Identification (1) To a quantity of Bisacodyl Supposito-ries, equivalent to 6 mg of Bisacodyl, add 20 mL of ethanol (95), warm on a water bath for 10 minutes, shake vigorously for 10 minutes, and allow to stand in ice water for 1 hour. Centrifuge the solution, filter the supernatant liquid, and to 2 mL of the filtrate add ethanol (95) to make 20 mL. Deter-mine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhib-its a maximum between 261 nm and 265 nm. (2) Use the filtrate obtained in (1) as the sample solution. Separately, dissolve 6 mg of Bisacodyl RS in 20 mL of ethanol (95), and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 20 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. De-velop the plate with a mixture of 2-butanone, chloroform and xylene (1:1:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot obtained from the sample solution and that from the standard solution show the same Rf value. Uniformity of dosage units <6.02> Perform the test accord-ing to the following method: it meets the requirement of the Content uniformity test. To 1 suppository of Bisacodyl Suppositories add a suitable amount of tetrahydrofuran, warm to 409C, and shake to dis-solve. After cooling, add tetrahydrofuran to make exactly V mL so that each mL contains about 0.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To a quantity of Bisacodyl Supposito-ries, equivalent to 6 mg of Bisacodyl, add 20 mL of ethanol (95), warm on a water bath for 10 minutes, shake vigorously for 10 minutes, and allow to stand in ice water for 1 hour. Centrifuge the solution, filter the supernatant liquid, and to 2 mL of the filtrate add ethanol (95) to make 20 mL. Deter-mine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhib-its a maximum between 261 nm and 265 nm. (2) Use the filtrate obtained in (1) as the sample solution. Separately, dissolve 6 mg of Bisacodyl RS in 20 mL of ethanol (95), and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 20 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. De-velop the plate with a mixture of 2-butanone, chloroform and xylene (1:1:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot obtained from the sample solution and that from the standard solution show the same Rf value. Uniformity of dosage units <6.02> Perform the test accord-ing to the following method: it meets the requirement of the Content uniformity test. To 1 suppository of Bisacodyl Suppositories add a suitable amount of tetrahydrofuran, warm to 409C, and shake to dis-solve. After cooling, add tetrahydrofuran to make exactly V mL so that each mL contains about 0.2 mg of bisacodyl (C22H19NO4). Pipet 5 mL of this solution, and proceed as directed in the Assay. Amount (mg) of bisacodyl (C22H19NO4) ＝ MS × QT/QS × V/50 JP XVIII Official Monographs / Bismuth Subgallate 555 MS: Amount (mg) of Bisacodyl RS taken Internal standard solution—A solution of ethyl parahy-droxybenzoate in acetonitrile (3 in 100,000). ‌Assay Weigh accurately not less than 20 Bisacodyl Sup-positories, make them fine fragmen…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity of solution—Dissolve 1.0 g of Bismuth Subgallate in 40 mL of diluted sodium hydroxide TS (1 in 8): the solution is clear. Sulfate—Ignite 3.0 g of Bismuth Subgallate in a por-celain crucible, and cautiously dissolve the residue in 2.5 mL of nitric acid by warming. Pour the solution into 100 mL of water, shake, and filter. Evaporate 50 mL of the filtrate on a water bath to 15 mL. Add water to make 20 mL, filter again, and use the filtrate as the sample solution. To 5 mL of the sample solution add 2 to 3 drops of barium nitrate TS: no Amount (mg) of bisacodyl (C 22H19NO4) ＝ M S × QT/QS turbidity is produced. Nitrate—To 0.5 g of Bismuth Subgallate add 5 mL of MS: Amount (mg) of Bisacodyl RS taken Internal standard solution—A solution of ethyl parahy-droxybenzoate in acetonitrile (3 in 100,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4 mm in inside diameter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of 0.01 mol/L citric acid TS, acetonitrile and methanol (2:1:1). Flow rate: Adjust so that the retention time of bisacodyl is about 8 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the internal standard and bisacodyl are eluted in this order with the resolution between these peaks being not less than 2.0. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of bisacodyl to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.

bisacodyl
type: ChemicalDrugMonograph
pref label:
  en: Bisacodyl
  ja: ビサコジル
monograph id: JP18-bisacodyl
publisher: JP
status: Official
version: 18
molecular formula: C22H19NO4
molecular weight: 361.39
definition:
  en: Bisacodyl, when dried, contains not less than 98.
appearance:
  en: Bisacodyl occurs as a white crystalline powder. It is freely soluble in acetic acid (100), soluble in acetone, slightly soluble in ethanol (95) and in diethyl ether, and prac- tically insoluble in water. It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bisacodyl in ethanol (95) (3 in 100,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Bisacodyl RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Bi-sacodyl, previously dried, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of dried Bisacodyl RS: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 1.0 g of Bisacodyl in 30 mL of acetone, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.35 mL of 0.01 mol/L hydrochloric acid VS add 30 mL of acetone, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.012z). Sulfate <1.14>—Dissolve 1.0 g of Bisacodyl in 2 mL of dilute hydrochloric acid, and add water to make 50 mL. Perform the test using this solution as the test solution. Pre-pare the control solution as follows: to 0.35 mL of 0.005 mol/L sulfuric acid VS add 2 mL of dilute hydrochloric acid and water to make 50 mL (not more than 0.017z). Heavy metals <1.07>—Proceed with 2.0 g of Bi- sacodyl according to Method 4, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 10 ppm). Related substances—Dissolve 0.20 g of Bisacodyl in 10 mL of acetone, and use this solution as the sample solu-tion. Pipet 1 mL of the sample solution, add acetone to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatog-raphy. Develop the plate with a mixture of 2-butanone, chlo- roform and xylene (1:1:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Bisacodyl, previ-ously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from orange-yellow to green (indicator: 0.5 mL of p-naphtholbenzein TS). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 36.14 mg of C22H19NO4
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

bismuth-subgallate
type: ChemicalDrugMonograph
pref label:
  en: Bismuth Subgallate
  ja: 次没食子酸ビスマス
monograph id: JP18-bismuth-subgallate
publisher: JP
status: Official
version: 18
definition:
  en: Bismuth Subgallate, when dried, contains not less than 47.
appearance:
  en: Bismuth Subgallate occurs as a yellow powder. It is odorless and tasteless. dilute sulfuric acid and 25 mL of iron (II) sulfate TS, shake well, and filter. Superimpose carefully 5 mL of the filtrate on sulfuric acid: no red-brown color develops at the zone of contact. Ammonium—Dissolve 1.0 g of Bismuth Subgallate in 5 mL of sodium hydroxide TS, and heat: the gas evolved does not change moistened red litmus paper to blue. Copper—To 5 mL of the sample solution obtained in (2) add 1 mL of ammonia TS, and filter: no blue color de-velops in the filtrate. Lead—Ignite 1.0 g of Bismuth Subgallate at about 5009C in a porcelain crucible, dissolve the residue in a smallest possible amount of nitric acid added dropwise, evaporate over a low flame to dryness , and cool. Add 5 mL of a solution of potassium hydroxide (1 in 6) to the residue, boil carefully for 2 minutes, cool, and centrifuge. Take the supernatant liquid in a test tube, add 10 drops of potassium chromate TS, and acidify the solution by adding acetic acid (100) dropwise: neither turbidity nor a yellow precipitate is produced. Silver—To 5 mL of the sample solution obtained in (2) add 0.5 mL of nitric acid and 2 to 3 drops of dilute hy-drochloric acid: no turbidity is produced. Alkaline earth metals and alkali metals—Boil 1.0 g of Bismuth Subgallate with 40 mL of diluted acetic acid (31) (1 in 2) for 2 minutes, cool, add water to make 40 mL, and filter. To 20 mL of the filtrate add 2 mL of dilute hydrochlo-ric acid, boil, immediately pass hydrogen sulfide thoroughly through the solution, filter the precipitate produced, and wash with water. Combine the filtrate and the washings, add 5 drops of sulfuric acid, and evaporate to dryness. Ignite as directed under Residue on Ignition <2.44>: the mass of the residue is not more than 5.0 mg. Arsenic <1.11>—Mix well 0.20 g of Bismuth Subgal-late with 0.20 g of calcium hydroxide, and ignite the mixture. Dissolve the residue in 5 mL of dilute hydrochloric acid, use this solution…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Bismuth Subgallate, previously dried, ignite at about 5009C for 30 minutes, and cool. Dissolve the residue in 5 mL of diluted nitric acid (2 in 5) by warming, and add water to make exactly 100 mL. Measure exactly 30 mL of this solution, add 200 mL of water, and titrate <2.50> with 0.02 mol/L disodium dihydro-gen ethylenediamine tetraacetate VS until the color of the so-lution changes from red-purple to yellow (indicator: 2 to 3 drops of xylenol orange TS). Each mL of 0.02 mol/L disodium dihydrogen ethylenediamine tetraacetate VS ＝ 4.180 mg of Bi
storage conditions:
  en: Containers—Well-closed contain-ers.

bismuth-subnitrate
type: ChemicalDrugMonograph
pref label:
  en: Bismuth Subnitrate
  ja: 次硝酸ビスマス
monograph id: JP18-bismuth-subnitrate
publisher: JP
status: Official
version: 18
definition:
  en: Bismuth Subnitrate, when dried, contains not less than 71.
appearance:
  en: Bismuth Subnitrate occurs as a white powder. It is practically insoluble in water, in ethanol (95) and in diethyl ether. It readily dissolves in hydrochloric acid and in nitric acid without effervescence. It is slightly hygroscopic, and changes moistened blue litmus paper to red.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Bismuth Subnitrate responds to Qualitative Tests <1.09> for bismuth salt and nitrate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 0.7 g of Bismuth Subnitrate in 2 mL of water and 2 mL of nitric acid, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: evaporate 2 mL of nitric acid on a water bath to dryness, add 0.70 mL of 0.01 mol/L hydro-chloric acid VS, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.035z). Sulfate—Dissolve 3.0 g of Bismuth Subnitrate in 3.0 mL of warmed nitric acid, pour this solution into 100 mL of water, shake, and filter. Concentrate the filtrate on a water bath to 30 mL, filter, and use this filtrate as the sample solu-tion. To 5 mL of the sample solution add 2 to 3 drops of barium nitrate TS: no turbidity is produced. Ammonium—Boil 0.10 g of bismuth Subnitrate with 5 mL of sodium hydroxide TS: the gas evolved does not change moistened red litmus paper to blue. Copper—To 5 mL of the sample solution obtained in (2) add 2 mL of ammonia TS, and filter: no blue color de-velops. Lead—To 1.0 g of Bismuth Subnitrate add 5 mL of a solution of sodium hydroxide (1 in 6), boil carefully for 2 minutes, cool and centrifuge. Transfer the supernatant liq-uid to a test tube, add 10 drops of potassium chromate TS, and add dropwise acetic acid (31) to render the solution acid: no turbidity or yellow precipitate is produced. Silver—To 5 mL of the sample solution obtained in (2) add 0.5 mL of nitric acid and 2 to 3 drops of dilute hy-drochloric acid: no turbidity is produced. Alkaline earth metals and alkali metals—Boil 2.0 g of Bismuth Subnitrate with 40 mL of diluted acetic acid (31) (1 in 2) for 2 minutes, cool, add water to make 40 mL, and filter. To 20 mL of the filtrate add 2 mL of dilute hydrochlo-ric acid, boil, immediately pass hydrogen sulfide thoroughly through the solution, filter, and wash the residue with water. Combine the filtrate and the washings, add 5 drops of sulfu-ric acid, evaporate to dryness, and ignite as dire…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Bismuth Subnitrate, previously dried, dissolve in 5 mL of diluted nitric acid (2 in 5) by warming, and add water to make exactly 100 mL. Pipet 25 mL of the solution, add 200 mL of water and titrate <2.50> with 0.02 mol/L disodium dihydrogen ethylene- diamine tetraacetate VS until the color of the solution changes from red-purple to yellow (indicator: 5 drops of xylenol orange TS) Each mL of 0.02 mol/L disodium dihydrogen ethylenediamine tetraacetate VS ＝ 4.180 mg of Bi
storage conditions:
  en: Containers—Well-closed contain-ers.

bisoprolol-fumarate
type: ChemicalDrugMonograph
pref label:
  en: Bisoprolol Fumarate
  ja: ビソプロロールフマル酸塩
monograph id: JP18-bisoprolol-fumarate
publisher: JP
status: Official
version: 18
definition:
  en: Bisoprolol Fumarate, when dried, contains not less than 98.
appearance:
  en: Bisoprolol Fumarate occurs as white crystals or a white crystalline powder. It is very soluble in water and in methanol, and freely soluble in ethanol (99.5) and in acetic acid (100). A solution of Bisoprolol Fumarate (1 in 10) shows no opti-cal rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bisoprolol Fumarate in methanol (1 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the ‌JP XVIII Official Monographs / Bisoprolol Fumarate Tablets 557 same wavelengths. Determine the infrared absorption spectrum of Bi-soprolol Fumarate as directed in the potassium bromide disc method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Bisoprolol Fumarate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 50 mg of Bisoprolol Fumarate in 100 mL of a mixture of water and acetonitrile (4:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mixture of water and acetonitrile (4:1) to make exactly 100 mL, and use this solu-tion as the standard solution. Perform the test with exactly Fumarate, previously dried, dissolve in 70 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (indicator: 2 drops of crystal violet TS). The endpoint of titration is when the purple color of the solution turns blue and then blue-green. Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 38.35 mg of (C18H31NO4)2.C4H4O4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bleomycin-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Bleomycin Hydrochloride
  ja: ブレオマイシン塩酸塩
monograph id: JP18-bleomycin-hydrochloride
publisher: JP
status: Official
version: 18
definition:
  en: Bleomycin Hydrochloride is the hydrochloride of a mixture of substances having antitumor activity pro-duced by the growth of Streptomyces verticillus. It contains not less than 1400 mg (potency) and not more than 2000 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Bleomycin Hydrochloride occurs as a white to yellow-white powder. It is freely soluble in water, and slightly soluble in ethanol (95). It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 4 mg of Bleomycin Hydrochloride add 5 mL of copper (II) sulfate TS, and dissolve in water to make 100 mL. Determine the absorption spectrum of this so-lution as directed under Ultraviolet-visible Spectrophotome-try <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wavelengths. Determine the infrared absorption spectrum of Bleomycin Hydrochloride as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Bleomycin Hydrochloride (1 in 100) re-sponds to Qualitative Tests <1.09> (2) for chloride. pH <2.54> The pH of a solution obtained by dissolving 0.10 g of Bleomycin Hydrochloride in 20 mL of water is be-tween 4.5 and 6.0. Content ratio of the active principle Dissolve 10 mg of Bleomycin Hydrochloride in 20 mL of water, and use this so-lution as the sample solution. Perform the test with 20 mL of the sample solution as directed under Liquid Chromatogra-phy <2.01> according to the following conditions, and deter-mine each peak area by the automatic integration method, and calculate their amounts by the area percentage method: the amount of the peak of bleomycin A2 (the first principal peak) is between 55z and 70z, that of bleomycin B2 (the second principal peak) is between 25z and 32z, the total amount of the peak of bleomycin A2 and bleomycin B2 is not less than 85z, the amount of the peak of demethylbleomy-cin A2 (a peak having the relative retention time of 1.5 – 2.5 to bleomycin A2) is not more than 5.5z, and the total amount of the rest peaks is not more than 9.5z. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution ob-tained by dissolving 80 mg of Bleomycin Hydrochloride in 4 mL of water is clear and colorless. Copper—Dissolve exactly 75 mg of Bleomycin Hy-drochloride in exactly 10 mL of diluted nitric acid (1 in 100), and use this solution as the sample solution. Separately, to exactly 15 mL of Standard Copper Solution add diluted nitric acid (1 in 100) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with the sample solution and standard solution as directed under Atomic Absorption Spectrophotometry <2.23> according to the following conditions: the absorbance of the sample solu-tion is not more than that of the standard solution (not more than 200 ppm). Gas: Combustible gas—Acetylene. Supporting gas—Air. Lamp: Copper hollow-cathode lamp. Wavelength: 324.8 nm. Loss on drying <2.41> Not more than 5.0z (60 mg, in vacuum, phosphorus (V) oxide, 609C, 3 hours. Take the sample to be tested while avoiding moisture absorption).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform the test according to the Cylinder-plate method as directed under Microbial Assay for Antibiotics <4.02> according to the following conditions. Test organism—Mycobacterium smegmatis ATCC 607 Agar medium for seed, base layer and transferring the test organism Mix all the components, and sterilize. Adjust the pH after sterilization to 6.9 – 7.1 with sodium hydroxide TS. Liquid media for suspending the test organism Glycerin 10.0 g Peptone 10.0 g Meat extract 10.0 g Sodium chloride 3.0 g Water 1000 mL Mix all the components, and sterilize. Adjust the pH after sterilization to 6.9 – 7.1 with sodium hydroxide TS. Preparation of seeded agar layer—Cultivate the test organism on the slant of the agar medium for transferring the test organism at 279C for 40 to 48 hours, then inoculate the test organism thus obtained in 100 mL of the liquid me-dia for suspending the test organism, cultivate with shaking at between 259C and 279C for 5 days, and use this as the sus-pension of test organism. Store the suspension of test organ-ism at a temperature not exceeding 59C, and use within 14 days. Add 0.5 mL of the suspension of test organism in 100 mL of the agar medium for seed previously kept at 489C, mix thoroughly, and use as the seeded agar layer. Preparation of cylinder-agar plate—Proceed as di-rected in 1.7. Preparation of cylinder-agar plates under the Microbial Assay for Antibiotics, dispensing 5.0 mL of agar medium for base layer and 8.0 mL of the agar medium for seed into the Petri dish. Standard solutions—Weigh accurately an amount of Bleomycin A2 Hydrochloride RS, previously dried under reduced pressure not exceeding 0.67 kPa at an ordinary tem-perature for 3 hours, equivalent to about 15 mg (potency), dissolve in 0.1 mol/L phosphate buffer solution (pH 6.8) to make exactly 100 mL, and use this solution as the standard stock solution. Keep the standard stock solution at 59C or below, and use within 30 days. Take exactly a suitable amount of the standard stock soluti…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bleomycin-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Bleomycin Sulfate
  ja: ブレオマイシン硫酸塩
monograph id: JP18-bleomycin-sulfate
publisher: JP
status: Official
version: 18
definition:
  en: Bleomycin Sulfate is the sulfate of a mixture of sub-stances having antitumor activity produced by the growth of Streptomyces verticillus. It contains not less than 1400 mg (potency) and not more than 2000 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Bleomycin Sulfate occurs as a white to yellow-white powder. It is freely soluble in water, and slightly soluble in ethanol (95). It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 4 mg of Bleomycin Sulfate add 5 mL of copper (II) sulfate TS, and dissolve in water to make 100 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bleomycin Sulfate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Bleomycin Sulfate (1 in 200) responds to Qualitative Tests <1.09> (1) and (2) for sulfate. pH <2.54> The pH of a solution obtained by dissolving 10 mg of Bleomycin Sulfate in 20 mL of water is between 4.5 and 6.0. Content ratio of the active principle Dissolve 10 mg of Bleomycin Sulfate in 20 mL of water, and use this solution as the sample solution. Perform the test with 20 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method, and calculate their amounts by the area percentage method: the amount of the peak of bleomycin A2 (the first principal peak) is between 55z and 70z, that of bleomycin B2 (the second principal peak) is between 25z and 32z, the total amount of the peak of bleomycin A2 and bleomycin B2 is not less than 85z, the amount of the peak of demethylbleomy-cin A2 (a peak having the relative retention time of 1.5 – 2.5 to bleomycin A2) is not more than 5.5z, and the total amount of the rest peaks is not more than 9.5z. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (7 mm in particle diameter). Co…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution ob-tained by dissolving 80 mg of Bleomycin Sulfate in 4 mL of water is clear and colorless. Copper—Dissolve exactly 75 mg of Bleomycin Sul-fate in 10 mL of diluted nitric acid (1 in 100), and use this so-lution as the sample solution. Separately, to exactly 15 mL of Standard Copper Solution add diluted nitric acid (1 in 100) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with the sample solution and standard solution as directed under Atomic Absorption Spectrophotometry <2.23> according to the following condi-tions: the absorbance of the sample solution is not more than that of the standard solution (not more than 200 ppm). Gas: Combustible gas—Acetylene. Supporting gas—Air. Lamp: Copper hollow-cathode lamp. Wavelength: 324.8 nm. Loss on drying <2.41> Not more than 3.0z (60 mg, in vacuum, phosphorus (V) oxide, 609C, 3 hours. Take the sample to be tested while avoiding moisture absorption).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform the test according to the Cylinder-plate method as directed under Microbial Assay for Antibiotics <4.02> according to the following conditions. Test organism—Mycrobacterium smegmatis ATCC 607 Agar medium for seed, base layer and transferring the test organism Glycerin 10.0 g Peptone 10.0 g Meat extract 10.0 g Sodium chloride 3.0 g Agar 15.0 g Water 1000 mL Mix all the components and sterilize. Adjust the pH after sterilization to 6.9 – 7.1 with sodium hydroxide TS. Liquid media for suspending the test organism Glycerin 10.0 g Peptone 10.0 g Meat extract 10.0 g Sodium chloride 3.0 g Water 1000 mL Mix all the components and sterilize. Adjust the pH after sterilization to 6.9 – 7.1 with sodium hydroxide TS. Preparation of seeded agar layer—Cultivate the test organism on the slant of the agar medium for transferring the test organism at 279C for 40 to 48 hours, then inoculate the test organism thus obtained in 100 mL of the liquid me-dia for suspending the test organism, cultivate with shaking at between 259C and 279C for 5 days, and use this as the sus-pension of test organism. Store the suspension of test organ-ism at a temperature not exceeding 59C, and use within 14 days. Add 0.5 mL of the suspension of test organism in 100 mL of the agar medium for seed previously kept at 489C, mix thoroughly, and use as the seeded agar layer. Preparation of cylinder-agar plate—Proceed as di-rected in 1.7. Preparation of cylinder-agar plates under the Microbial Assay for Antibiotics, dispensing 5.0 mL of agar medium for base layer and 8.0 mL of the agar medium for seed into the Petri dish. Standard solutions—Weigh accurately an amount of Bleomycin A2 Hydrochloride RS, previously dried under reduced pressure not exceeding 0.67 kPa at an ordinary tem-perature for 3 hours, equivalent to about 15 mg (potency), dissolve in 0.1 mol/L phosphate buffer solution (pH 6.8) to make exactly 100 mL, and use this solution as the standard stock solution. Keep the standard stock solution at…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bofutsushosan-extract
type: ChemicalDrugMonograph
pref label:
  en: Bofutsushosan Extract
  ja: 防風通聖散エキス
monograph id: JP18-bofutsushosan-extract
publisher: JP
status: Official
version: 18
definition:
  en: Bofutsushosan Extract contains not less than 9 mg and not more than 36 mg of paeoniflorin (C23H28O11: 480.
appearance:
  en: Bofutsushosan Extract is a yellow-brown to brown powder or black-brown viscous extract. It has a slightly odor and a sweet and slightly bitter taste. Identiˆcation (1) To 2.0 g of the dry extract (or 6.0 g of the viscous extract) add 10 mL of water, shake, then add 10 mL of diethyl ether, shake, and centrifuge. Separate the diethyl ether layer, add 10 mL of sodium hydroxide TS, shake, centrifuge, and use the diethy ether layer as the sam-ple solution. Separately, use (Z)-ligustilide TS for thin-layer chromatography as the standard solution. Perform the test with these solutions as directed under Thin-layer Chro-matography <2.03>. Spot 20 mL of the sample solution and 10 mL of the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of butyl acetate and hexane (2:1) to a distance of about 7 cm, and air-dry the plate. Examine under ultraviolet light (main Bofutsushosan Extract / Crude Drugs and Related Drugs wavelength: 365 nm): one of the several spots obtained from the sample solution has the same color tone and Rf value with the blue-white ‰uorescent spot from the standard solu-tion (Japanese Angelica Root; Cnidium Rhizome). To 1.0 g of the dry extract (or 3.0 g of the viscous extract) add 10 mL of water, shake, then add 10 mL of 1-butanol, shake, centrifuge, and use the 1-butanol layer as the sample solution. Separately, dissolve 1 mg of paeoniflorin for thin-layer chromatography in 1 mL of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 10 mL of the sample solution and 5 mL of the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, methanol and ammonia solution (28) (6:3:2) to a distance of about 7 cm, and air-dry the plate. Spray evenly 4-methoxybenzaldehyde-sulfuric acid TS on the plate, heat the plate at 1059C for 1 minute: one of …
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Prepare the test solution with 1.0 g of the dry extract (or an amount of the viscous ex-tract, equivalent to 1.0 g of the dried substance) as directed under Extracts (4), and perform the test (not more than 30 ppm). (2) Arsenic <1.11>—Prepare the test solution with 0.67 g of the dry extract (or an amount of the viscous extract, equivalent to 0.67 g of the dried substance) according to Method 3, and perform the test (not more than 3 ppm). Loss on drying <2.41> The dry extract: Not more than 9.0z (1 g, 1059C, 5 hours). The viscous extract: Not more than 66.7z (1 g, 1059C, 5 hours). Total ash <5.01> Not less than 10.0z and more than 22.0z, calculated on the dried basis.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Paeoniflorin—Weigh accurately about 0.5 g of the dry extract (or an amount of the viscous extract, equiva-lent to about 0.5 g of the dried substance), add exactly 50 mL of diluted methanol (1 in 2), shake for 15 minutes, and filter. Pipet 5 mL of the filtrate, elute through a column packed with 2 g of polyamide for column chromatography using 20 mL of water, then add 1 mL of acetic acid (100), add water to make exactly 25 mL, and use this solution as the sample solution. Separately, weigh accurately about 10 mg of Paeoniflorin RS (separately determine the water <2.48> by coulometric titration, using 10 mg), and dissolve in diluted methanol (1 in 2) to make exactly 100 mL. Pipet 5 mL of this solution, add diluted methanol (1 in 2) to make MS: Amount (mg) of Paeoniflorin RS taken, calculated on the anhydrous basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 232 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 209C. Mobile phase: A mixture of water, acetonitrile and phos-phoric acid (850:150:1). Flow rate: 1.0 mL per minute (the retention time of paeoniflorin is about 9 minutes). System suitability— System performance: Dissolve 1 mg each of Paeoniflorin RS and albiflorin in diluted methanol (1 in 2) to make 10 mL. When the procedure is run with 10 mL of this solu-tion under the above operating conditions, albiflorin and paeoniflorin are eluted in this order with the resolution be-tween these peaks being not less than 2.5. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of paeoniflorin is not more than 1.5z. Total alkaloids (ephedrine and pseudoephedrine)—Weigh accurately about 0.5 g of the dry extract (or an amount…
storage conditions:
  en: Containers—Tight containers.

boiogito-extract
type: ChemicalDrugMonograph
pref label:
  en: Boiogito Extract
  ja: 防已黄耆湯エキス
monograph id: JP18-boiogito-extract
publisher: JP
status: Official
version: 18
definition:
  en: Boiogito Extract contains not less than 4 mg and not more than 16 mg of sinomenine, and not less than 10 mg and not more than 30 mg of glycyrrhizic acid rately, dissolve 1.
appearance:
  en: Boiogito Extract is a light yellow-brown to reddish brown powder or black-brown viscous extract. It has a slightly odor, and a sweet taste at first and then a slight hot and bitter taste later.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2.0 g of the dry extract (or 6.0 g of the viscous extract) add 15 mL of sodium hydroxide TS, shake, centrifuge, and separate the supernatant liquid. To this liquid add 10 mL of 1-butanol, shake, centrifuge, and separate 1-butanol layer. To this liquid add 10 mL of water, shake, centrifuge, separate the 1-butanol layer, then evapo-rate the solvent under low pressure (in vacuo), dissolve the residue in 1 mL of methanol, and use the solution as the sample solution. Separately, dissolve 1 mg of sinomenine for thin-layer chromatography in 1 mL of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 10 mL of the sample solution and 2 mL of the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, 1-propanol, water and acetic acid (100) (7:5:4:1) to a distance of about 7 cm, and air-dry the plate. Spray evenly 4-dimethylaminobenzaldehyde TS for spraying on the plate, heat the plate at 1059C for 5 minutes, and allow to cool: one of the several spots obtained from the sample solution has the same color tone and Rf value with the red to red-brown spot from the standard solution (Sinomenium Stem and Rhi-zome). To 2.0 g of the dry extract (or 6.0 g of the viscous ex-tract) add 15 mL of sodium hydroxide TS, shake, centrifuge, and separate the supernatant liquid. To this liquid add 10 mL of 1-butanol, shake, centrifuge, and separate 1-butanol layer. To the aqueous layer add 10 mL of 1-butanol, and proceed in the same manner as above. Combine the 1-butanol layers, add 10 mL of water, shake, centrifuge, sepa-rate the 1-butanol layer, and evaporate the solvent under low pressure (in vacuo). Dissolve the residue in exactly 1 mL of methanol, and use this solution as the sample solution. Sepa- heat the plate at 1059C for 5 minutes, and allow to cool: one of the several spots obtained from the sample solution h…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Prepare the test solution with 1.0 g of the dry extract (or an amount of the viscous ex-tract, equivalent to 1.0 g of the dried substance) as directed under Extracts (4), and perform the test (not more than 30 ppm). (2) Arsenic <1.11>—Prepare the test solution with 0.67 g of the dry extract (or an amount of the viscous extract, equivalent to 0.67 g of the dried substance) according to Method 3, and perform the test (not more than 3 ppm). Loss on drying <2.41> The dry extract: Not more than 11.0z (1 g, 1059C, 5 hours). The viscous extract: Not more than 66.7z (1 g, 1059C, 5 hours). Total ash <5.01> Not less than 8.0z, calculated on the dried basis. However, for the dry extract prepared by adding Light Anhydrous Silicic Acid, between 9.0z and 18.0z.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Sinomenine—Weigh accurately about 0.5 g of the dry extract (or an amount of the viscous extract, equiva-lent to about 0.5 g of the dried substance), add 20 mL of Operating conditions— Detector: An ultraviolet absorption photometer (wavelength: 254 nm). Column: A stainless steel column 4.6 mm in inside di-ameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle di-ameter). Column temperature: A constant temperature of about 309C. Mobile phase: To 3 g of sodium lauryl sulfate add 350 mL of acetonitrile, shake, then add 650 mL of water and 1 mL of phosphoric acid to dissolve lauryl sulfate. Flow rate: 1.0 mL per minute (the retention time of sinomenine is about 18 minutes). System suitability— System performance: When the procedure is run with 10 mL each of the sample solution, the sinomenine standard so-lution and the glycyrrhizic acid standard solution obtained in Assay (2) under the above operating conditions, peaks of sinomenine and glycyrrhizic acid are observed in the sample solution, glycyrrhizic acid and sinomenine are eluted in this order with the resolution between these peaks being not less than 4.5. Furthermore, except for the peak of glycyrrhizic acid, distinct peaks are observed before and after the peak of sinomenine, and the resolutions between sinomenine and these peaks are respectively not less than 1.5. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of sinomenine is not more than 1.5z. (2) Glycyrrhizic acid—Weigh accurately about 0.5 g of the dry extract (or an amount of the viscous extract, equiva-lent to about 0.5 g of the dried substance), add exactly 50 mL of diluted methanol (1 in 2), shake for 15 minutes, filter, and use the filtrate as the sample solution. Separately, weigh accurately about 10 mg of Glycyrrhizic Acid RS (separately determine the water <…
storage conditions:
  en: Containers—Tight containers.

boric-acid
type: ChemicalDrugMonograph
pref label:
  en: Boric Acid
  ja: ホウ酸
monograph id: JP18-boric-acid
publisher: JP
status: Official
version: 18
molecular formula: H3BO3
molecular weight: 61.83
definition:
  en: Boric Acid, when dried, contains not less than 99.
appearance:
  en: Boric Acid occurs as colorless or white, crys-tals or crystalline powder. It is odorless, and has a slight, characteristic taste. It is freely soluble in warm water, in hot ethanol (95) and in glycerin, soluble in water and in ethanol (95), and practi-cally insoluble in diethyl ether. The pH of a solution of 1.0 g of Boric Acid in 20 mL of water is between 3.5 and 4.1.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: A solution of Boric Acid (1 in 20) responds to Qualitative Tests <1.09> for borate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Boric Acid in 25 mL of water or in 10 mL of hot ethanol (95): the solution is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g of Boric Acid according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution ‌JP XVIII Official Monographs / Bromfenac Sodium Hydrate 563‌‌ (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 0.40 g of Boric Acid according to Method 1, and perform the test (not more than 5 ppm). Loss on drying <2.41> Not more than 0.5z (2 g, silica gel, 5 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 1.5 g of Boric Acid, previ-ously dried, add 15 g of D-sorbitol and 50 mL of water, and dissolve by warming. After cooling, titrate <2.50> with 1 mol/L sodium hydroxide VS (indicator: 2 drops of phenol-phthalein TS). Each mL of 1 mol/L sodium hydroxide VS ＝ 61.83 mg of H3BO3
storage conditions:
  en: Containers—Well-closed contain-ers.

bromazepam
type: ChemicalDrugMonograph
pref label:
  en: Bromazepam
  ja: ブロマゼパム
monograph id: JP18-bromazepam
publisher: JP
status: Official
version: 18
molecular formula: C14H10BrN3O
molecular weight: 316.15
cas number: 1812-30-2
definition:
  en: Bromazepam, when dried, contains not less than 99.
appearance:
  en: Bromazepam occurs as white to light yellow-white, crystals or crystalline powder. It is freely soluble in acetic acid (100), slightly soluble in methanol, in ethanol (99.5) and in acetone, and practically insoluble in water. Melting point: about 2459C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bromazepam in ethanol (99.5) (1 in 200,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bromazepam, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Bromazepam in a platinum crucible according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 50 mg of Bromazepam in 5 mL of a mixture of acetone and methanol (3:2), and use this solution as the sample solution. Pipet 1 mL of the sam-ple solution, and add the mixture of acetone and methanol (3:2) to make exactly 50 mL. Pipet 5 mL of this solution, add the mixture of acetone and methanol (3:2) to make ex-actly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 20 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. De-velop the plate with a mixture of ethyl acetate, ammonia so-lution (28) and ethanol (99.5) (38:1:1) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the princi-pal spot obtained from the sample solution and the spot of the starting point are not more than 2, and not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.20z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Bromazepam, pre-viously dried, dissolve in 80 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 31.62 mg of C14H10BrN3O
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

bromhexine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Bromhexine Hydrochloride
  ja: ブロムヘキシン塩酸塩
monograph id: JP18-bromhexine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C14H20Br2N2.HCl
molecular weight: 412.59
definition:
  en: Bromhexine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Bromhexine Hydrochloride occurs as white, crystals or crystalline powder. It is freely soluble in formic acid, sparingly soluble in methanol, and slightly soluble in water and in ethanol (95). The pH of its saturated solution is between 3.0 and 5.0. Melting point: about 2399C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 3 mg of Bromhexine Hydro-chloride in 0.01 mol/L hydrochloric acid TS to make 100 mL. Determine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bromhexine Hydrochloride, previously dried, as directed in the potassium bromide disk method under Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. Add 20 mL of water to 1 g of Bromhexine Hydro-chloride. After thorough shaking, add 3 mL of sodium hy-droxide TS, and extract with four 20-mL portions of diethyl ether. Neutralize the water layer with dilute nitric acid: the solution responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Bromhexine Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 50 ‌566 mg of Bromhexine Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add the mobile phase to make exactly 20 mL. Pipet 1 mL of this solution, add the mobile phase to make exactly 25 mL, and use this solution as the standard solution. Perform the test with exactly 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: each peak area other than bromhexine obtained from the sample solution is not larger than the peak area of bromhexine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 245 nm). Column: A stainless steel column about 5 mm in inside diameter and about 15 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 1.0 g of potassium dihydrogen phosphate in 900 mL of water, adjust the pH to 7.0 with 0.5 mol/L sodium hydroxide TS, and add water to make 1000 mL. To 200 mL of this solution add 800 mL of acetonitrile. Flow rate: Adjust so that the retention time of bromhexine is about 6 minutes. Selection of column: To 0.05 g of bamethan sulfate add 0.5 mL of the sample solution, and add the mobile phase to make 10 mL. Proceed with 5 mL of this solution under the above operating conditions, and calculate the resolution. Use a column giving elution of bamethan and bromhexine in this order with the resolution between these peaks bei…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Bromhexine Hydro-chloride, previously dried, dissolve in 2 mL of formic acid, add 60 mL of acetic anhydride, and warm in a water bath at 509C for 15 minutes. After cooling, titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue-green to yellow-green (indicator: 2 drops of crystal violet TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 41.26 mg of C14H20Br2N2.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

bromocriptine-mesilate
type: ChemicalDrugMonograph
pref label:
  en: Bromocriptine Mesilate
  ja: ブロモクリプチンメシル酸塩
monograph id: JP18-bromocriptine-mesilate
publisher: JP
status: Official
version: 18
molecular formula: C32H40BrN5O5.CH4O3S
molecular weight: 750.7
cas number: 22260-51-1
definition:
  en: Bromocriptine Mesilate contains not less than 98.
appearance:
  en: Bromocriptine Mesilate occurs as a white to pale yellowish white or pale brownish white crystalline powder. It is odorless, or has a faint characteristic odor. It is very soluble in acetic acid (100), freely soluble in methanol, sparingly soluble in ethanol (95), very slightly soluble in acetic anhydride, in dichloromethane and in chlo-roform, and practically insoluble in water and in diethyl ether. It is gradually colored by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 2 mg of Bromocriptine Mesi-late in 1 mL of methanol, add 2 mL of 4-dimethylaminoben-zaldehyde-ferric chloride TS, and shake: a purplish blue color develops. Determine the absorption spectrum of a solution of Bromocriptine Mesilate in methanol (3 in 100,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bromocriptine Mesilate as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Bromocriptine Mesilate as di-rected under Flame Coloration Test <1.04> (2): a green color appears. D Optical rotation <2.49> [a]20: ＋95 – ＋1059[0.1 g, calcu-lated on the dried basis, a mixture of methanol and dichloro-methane (1:1), 10 mL, 100 mm].
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.10 g of Bromocriptine Mesilate in 10 mL of methanol: the solu-tion is clear, and has no more color than the following con-trol solution. Control solution: To 2.5 mL of Cobalt (II) Chloride CS, 6.0 mL of Iron (III) Chloride CS and 1.0 mL of Copper (II) Sulfate CS add diluted hydrochloric acid (1 in 40) to make exactly 100 mL. Heavy metals <1.07>—Proceed with 1.0 g of Bromocriptine Mesilate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). ‌JP XVIII Official Monographs / Bromovalerylurea 567 Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 0.10 g of Bromocriptine Mesilate in 10 mL of a mixture of methanol and chloroform (1:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of methanol and chloroform (1:1) to make exactly 200 mL, and use this solution as the standard solution (1). Pipet 10 mL of the standard solution (1), add a mixture of methanol and chloroform (1:1) to make exactly 20 mL, and use this solution as the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chro-matography <2.03>. Spot 10 mL each of the sample solution and standard solutions (1) and (2), as a band with 1 cm in width, on a plate of silica gel for thin-layer chromatography. Develop the plate immediately with a mixture of dichloro-methane, 1,4-dioxane, ethanol (95) and ammonia solution (28) (1800:150:50:1) to a distance of about 10 cm, and dry the plate under reduced pressure for 30 minutes. Spray evenly Dragendorff's TS for spraying on the plate, then spray evenly hydrogen peroxide TS, cover the plate with a glass plate, and examine: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution (1), and the spot other than the principal spot, whi…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Bromocriptine Mesilate, dissolve in 80 mL of a mixture of acetic anhydride and acetic acid (100) (7:1), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 75.07 mg of C32H40BrN5O5.CH4O3S
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant, and not exceeding －189C.
type: PharmacopoeiaMonograph

bromovalerylurea
type: ChemicalDrugMonograph
pref label:
  en: Bromovalerylurea
  ja: ブロモバレリル尿素
monograph id: JP18-bromovalerylurea
publisher: JP
status: Official
version: 18
molecular formula: C6H11BrN2O2
molecular weight: 223.07
definition:
  en: Bromovalerylurea, when dried, contains not less than 98.
appearance:
  en: Bromovalerylurea occurs as colorless or white, crystals or crystalline powder. It is odorless, and has a slightly bitter taste. It is soluble in ethanol (95), sparingly soluble in diethyl ether, and very slightly soluble in water. It dissolves in sulfuric acid, in nitric acid and in hydro-chloric acid, and precipitates are produced on the addition of water. It dissolves in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Boil 0.2 g of Bromovalerylurea with 5 mL of a solution of sodium hydroxide (1 in 10): the gas evolved changes moistened red litmus paper to blue. Boil this solution with an excess of dilute sulfuric acid: the odor of valeric acid is perceptible. (2) To 0.1 g of Bromovalerylurea add 0.5 g of anhydrous sodium carbonate, and decompose thoroughly by gentle heating. Dissolve the residue in 5 mL of hot water, cool, acidify with acetic acid (31), and filter: the filtrate responds to Qualitative Tests <1.09> (2) for bromide.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity or alkalinity—To 1.5 g of Bromovalerylurea add 30 mL of water, shake for 5 minutes, and filter: the filtrate is neutral. Chloride <1.03>—Perform the test with a 10-mL por- tion of the filtrate obtained in (1). Prepare the control solu-tion with 0.40 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.028z). Sulfate <1.14>—Perform the test with 10 mL of the filtrate obtained in (1). Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not more than 0.038z). Heavy metals <1.07>—Proceed with 2.0 g of Bromovalerylurea according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Dissolve 0.5 g of Bromovalerylurea in 5 mL of sodium hydroxide TS, use this solution as the test solution, and perform the test (not more than 4 ppm). Readily carbonizable substances <1.15>—Perform the test with 0.5 g of Bromovalerylurea: the solution is not more colored than Matching Fluid A. Loss on drying <2.41> Not more than 0.5z (1 g, 809C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Bromovalerylurea, previously dried, in a 300-mL conical flask, add 40 mL of sodium hydroxide TS, and boil gently for 20 minutes under a reflux condenser. Cool, wash the lower part of the reflux condenser and the mouth of the flask with 30 mL of water, and combine the washings with the solution in the conical flask. Add 5 mL of nitric acid and exactly 30 mL of 0.1 mol/L silver nitrate VS, and titrate <2.50> the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indica-tor: 2 mL of ammonium iron (III) sulfate TS). Perform a blank determination in the same manner. Each mL of 0.1 mol/L silver nitrate VS ＝ 22.31 mg of C6H11BrN2O2
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

brotizolam
type: ChemicalDrugMonograph
pref label:
  en: Brotizolam
  ja: ブロチゾラム
monograph id: JP18-brotizolam
publisher: JP
status: Official
version: 18
molecular formula: C15H10BrClN4S
molecular weight: 393.69
definition:
  en: Brotizolam, when dried, contains not less than 98.
appearance:
  en: Brotizolam occurs as a white or pale yellow crystalline powder. It is sparingly soluble in methanol, slightly soluble in acetonitrile and in ethanol (99.5), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Brotizolam in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Brotizolam as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Brotizolam according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 50 mg of Brotizolam in 50 mL of acetonitrile, and use this solution as the sample solution. Pipet 2 mL of the sample solution, and add aceto-nitrile to make exactly 100 mL. Pipet 1 mL of this solution, add acetonitrile to make exactly 10 mL, and use this solution as the standard solution. Perform the test with exactly 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method: each peak area other than brotizolam obtained from the sample solution is not larger than 1/2 times the peak area of brotizolam from the stand-ard solution, and the total area of the peaks other than brotizolam from the sample solution is not larger than the peak area of brotizolam from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 242 nm). Column: A stainless steel column 3.9 mm in inside diame-ter and 15 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Flow rate: About 2 mL per minute. Time span of measurement: About 2 times as long as the retention time of brotizolam, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 5 mL of the standard solution, and add acetonitrile to make exactly 20 mL. Con-firm that the peak area of brotizolam obtained with 5 mL of this solution is equivalent to 18 to 32z of that with 5 mL of the standard solution. System performance: When the procedure is run with 5 mL of the standard solution under the above operating condi-tions, the number of theoretical plates and the symmetry fac-tor o…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of Brotizolam, previ-ously dried, dissolve in 75 mL of a mixture of acetic anhy-dride and acetic acid (100) (2:1), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 19.68 mg of C15H10BrClN4S
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.

bucillamine
type: ChemicalDrugMonograph
pref label:
  en: Bucillamine
  ja: ブシラミン
monograph id: JP18-bucillamine
publisher: JP
status: Official
version: 18
molecular formula: C7H13NO3S2
molecular weight: 223.31
cas number: 65002-17-7
definition:
  en: Bucillamine, when dried, contains not less than 98.
appearance:
  en: Bucillamine occurs as white, crystals or crys-talline powder. It is freely soluble in methanol and in ethanol (95), and slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Bucillamine (1 in 250) add 2 mL of sodium hydroxide TS and 2 drops of so-dium pentacyanonitrosylferrate (III) TS: the solution reveals a red-purple color. (2) Determine the infrared absorption spectrum of Bucil-lamine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋33.0 – ＋36.59(after dry-ing, 2 g, ethanol (95), 50 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Bucillamine according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Bucillamine according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 60 mg of Bucillamine in 20 mL of a mixture of water and methanol (1:1), and use this solution as the sample solution. Pipet 3 mL of the sam-ple solution, add the mixture of water and methanol (1:1) to make exactly 200 mL, and use this solution as the standard solution. Immediately perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine each peak area by the au-tomatic integration method: the peak areas of related sub-stances, having the relative retention time of about 2.3 and about 3.1 to bucillamine, obtained from the sample solution are not larger than 8/15 times and 2/5 times the peak area of bucillamine from the standard solution, respectively, and the area of the peak other than the bucillamine and the peaks mentioned above from the sample solution is not larger than 1/5 times the peak area of bucillamine from the standard so-lution. The total area of the peaks other than bucillamine from the sample solution is not larger than the peak area of bucillamine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 6.0 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of 0.01 mol/L citric acid TS and methanol (1:1). Flow rate: Adjust so that the retention time of bucillamine is about 5 minutes. Time span of measurement: Ab…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of Bucillamine, dis-solve in 35 mL of methanol, add 15 mL of water, and titrate <2.50> with 0.05 mol/L iodine VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.05 mol/L iodine VS ＝ 11.17 mg of C7H13NO3S2
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bucumolol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Bucumolol Hydrochloride
  ja: ブクモロール塩酸塩
monograph id: JP18-bucumolol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C17H23NO4.HCl
molecular weight: 341.83
cas number: 36556-75-9
definition:
  en: Bucumolol Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Bucumolol Hydrochloride occurs as white, crystals or crystalline powder. It is freely soluble in water, sparingly soluble in methanol and in ethanol (95), slightly soluble in acetic acid (100), and practically insoluble in diethyl ether. Melting point: about 2289C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Bucumolol Hydro-chloride in 10 mL of diluted ethanol (95) (1 in 2), and ob-serve under ultraviolet light (main wavelength: 365 nm): the solution shows a yellow-green fluorescence. Render this so-lution alkaline by adding sodium hydroxide TS: the fluores-cence disappears. Acidify the solution by adding dilute hy-drochloric acid: the fluorescence reappears. Dissolve 0.1 g of Bucumolol Hydrochloride in 5 mL of water, and add 5 drops of Reinecke salt TS: a light red precipitate is formed. Determine the absorption spectrum of a solution of Bucumolol Hydrochloride (1 in 60,000) as directed under Ul-traviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bucumolol Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of solution, add methanol to make exactly 25 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of methanol and ammonia-ammonium chloride buffer solu-tion (pH 10.7) (30:1) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wave-length: 254 nm): the spots other than the principal spot ob-tained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 5 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Bucumolol Hydro-chloride, previously dried, add 45 mL of acetic acid (100), dissolve by warming at 609C, and cool. Add 105 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchlo-ric acid VS (potentiometric titration). Perform a blank deter-mination in the same manner, and make any necessary cor-rection. Each mL of 0.1 mol/L perchloric acid VS ＝ 34.18 mg of C17H23NO4.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

bufetolol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Bufetolol Hydrochloride
  ja: ブフェトロール塩酸塩
monograph id: JP18-bufetolol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C18H29NO4.HCl
molecular weight: 359.89
definition:
  en: Bufetolol Hydrochloride, when dried, contains not less than 98.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Bufetolol Hydrochloride (1 in 100) add 5 drops of Reinecke salt TS: a light red precipitate is formed. Determine the absorption spectrum of a solution of Bufetolol Hydrochloride (1 in 20,000) as directed under Ul-traviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bufetolol Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectropho- JP XVIII Official Monographs / Buformin Hydrochloride 573 tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. ‌A solution of Bufetolol Hydrochloride (1 in 50) re-sponds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Bucumolol Hydrochloride in 20 mL of water: the solution is clear and colorless to pale yellow. Heavy metals <1.07>—Proceed with 1.0 g of Bucumolol Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Bucumolol Hydrochloride according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of Bucumolol Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add methanol to make exactly 50 mL. Pipet 5 mL of this ble in diethyl ether. A solution of Bufetolol Hydrochloride (1 in 10) shows no optical rotation. Identification (1) To 5 mL of a solution of Bufetolol Hydrochloride (1 in 100) add 5 drops of Reinecke salt TS: a light red precipitate is formed. Determine the absorption spectrum of a solution of Bufetolol Hydrochloride (1 in 20,000) as directed under Ul-traviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bufetolol Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectropho- JP XVIII Official Monographs / Buformin Hydrochloride 573 tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. ‌A solution of Bufetolol Hydrochloride (1 in 50) re-sponds to Qualitative Tests <1.09> for chloride. Melting point <2.60> 153 – 1579C Purity (1) Clarity and color of solution—Dissolve 1.0 g of Bufetolol Hydrochloride in 10 mL of water: the solution is clear and colorless. Sulfate <1.14>—Perform the test with 0.5 g of Bufetolol Hydrochloride. Prepare the control solution…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Bufetolol Hydro-chloride, previously dried, dissolve in 10 mL of acetic acid (100), add 50 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 35.99 mg of C18H29NO4.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bufonis-crustum
type: ChemicalDrugMonograph
pref label:
  en: Bufonis Crustum
  ja: センソ
monograph id: JP18-bufonis-crustum
publisher: JP
status: Official
version: 18
appearance:
  en: A round disk with slightly dented bottom and protuberant surface, about 8 cm in diameter, about 1.5 cm in thickness, the mass of one disk being about 80 to 90 g; or a round disk with almost ‰attened surfaces on both sides, about 3 cm in diameter, and about 0.5 cm in thickness, the mass of one disk being about 8 g; externally red-brown to black-brown, somewhat lustrous, approximately uniform and horny, hard in texture, and diŠicult to break; fractured surface nearly ‰at, and edges of broken pieces red-brown and translucent. Odorless.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 0.3 g of pulverized Toad Cake add 3 mL of acetone, shake for 10 minutes, filter, and use the filtrate as the sample solution. Separately, dissolve 1 mg of resibufogenin for thin-layer chromatography in 2 mL of ace-tone, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solu-tion and standard solution on a plate of silica gel for thin-layer chromatography, develop the plate with a mixture of cyclohexane and acetone (3:2) to a distance of about 10 cm, and air-dry the plate. Spray evenly dilute sulfuric acid on the plate, and heat the plate at 1059C for 5 minutes: one of the several spots obtained from the sample solution has the same color tone and Rf value with the spot from the standard so-lution. Total ash <5.01> Not more than 5.0z. Acid-insoluble ash <5.01> Not more than 2.0z.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of pulverized Toad Amount (mg) of resibufogenin ＝ MSR × QTR/QSR MSB: Amount (mg) of bufalin for assay taken MSC: Amount (mg) of cinobufagin for assay taken MSR: Amount (mg) of resibufogenin for assay taken Internal standard solution—A solution of indometacin in methanol (1 in 4000). Operating conditions— Detector: An ultraviolet spectrophotometer (wavelength: 300 nm). Column: A stainless steel column 4 to 6 mm in inside di-ameter and 15 to 30 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 to 10 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of diluted phosphoric acid (1 in 1000) and acetonitrile (11:9). Flow rate: Adjust so that the retention time of the internal standard is 16 to 19 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, bufalin, cinobufagin, resibufogenin and the internal standard are eluted in this order with the resolution among these peaks being not less than 1.5.
storage conditions:
  en: Containers—Well-closed contain-ers.

buformin-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Buformin Hydrochloride
  ja: ブホルミン塩酸塩
monograph id: JP18-buformin-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C6H15N5.HCl
molecular weight: 193.68
definition:
  en: Buformin Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Buformin Hydrochloride occurs as a white crystalline powder. It is freely soluble in water and in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Buformin Hydrochloride (1 in 2000) add 1 mL of dilute sodium penta-cyanonitrosylferrate (III)-potassium hexacyanoferrate (III) TS: a red-brown color develops. Determine the absorption spectrum of a solution of Buformin Hydrochloride (1 in 125,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave-lengths. Determine the infrared absorption spectrum of Buformin Hydrochloride as directed in the potassium chlo-ride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Buformin Hydrochloride (1 in 20) re-sponds to the Qualitative Tests <1.09> for chlorides.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Buformin Hydrochloride according to Method 1, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Buformin Hydrochloride according to Method 1, and per-form the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of Buformin Hydrochloride in 200 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample so-lution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area of both solutions by the automatic integration method: the area of the peak other than buformin obtained from the sample solution is not larger than 1/5 times the peak area of buformin from the standard solution. Further-more, the total areas of all peaks other than the buformin peak from the sample solution is not larger than 1/2 times the peak area of buformin from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 230 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 359C. Mobile phase: A mixture of a solution of sodium perchlorate monohydrate in diluted phosphoric acid (1 in 1000) (7 in 250) and acetonitrile (7:1). Flow rate: Adjust so that the retention time of buformin is about 6 minutes. Time span of measurement: About 2 times as long as the retention time of buformin, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 1 mL of the standard solution, and add the mobile phase to m…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of Buformin Hydro-chloride, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and immediately titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 9.684 mg of C6H15N5.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bumetanide
type: ChemicalDrugMonograph
pref label:
  en: Bumetanide
  ja: ブメタニド
monograph id: JP18-bumetanide
publisher: JP
status: Official
version: 18
molecular formula: C17H20N2O5S
molecular weight: 364.42
definition:
  en: Bumetanide, when dried, contains not less than 98.
appearance:
  en: Bumetanide occurs as white, crystals or crys-talline powder. It is freely soluble in pyridine, soluble in methanol and in ethanol (95), slightly soluble in diethyl ether, and practically insoluble in water. It dissolves in potassium hydroxide TS. It is gradually colored by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Bumetanide in 1 mL of pyridine, add 2 drops of copper (II) sulfate TS, shake, add 3 mL of water and 5 mL of chloroform, shake, and allow to stand: a light blue color develops in the chloroform layer. Dissolve 0.04 g of Bumetanide in 100 mL of phos-phate buffer solution (pH 7.0) and dilute 10 mL of the solu-tion with water to make 100 mL. Determine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi-ties of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bumetanide, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 50 mg of Bumetanide in 2 mL of a solution of potassium hydroxide (1 in 30) and 8 mL of water: the solution is clear, and is not more colored than the following control solution. Control solution: Pipet 0.5 mL each of Cobalt (II) Chlo-ride CS, Iron (III) Chloride CS and Copper (II) Sulfate CS, washing, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Heavy metals <1.07>—Proceed with 2.0 g of Bumetanide according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Bumetanide according to Method 3, and perform the test (not more than 2 ppm). Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 0.10 g of Bumetanide in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add methanol to make exactly 100 mL. Pipet 2 mL of this solution, add methanol to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform, acetic acid (100), cyclohexane and methanol (32:4:4:1) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Bumetanide, previ-ously dried, dissolve in 50 mL of ethanol (95), and titrate <2.50> with 0.1 mol/L sodium hydroxide VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 36.44 mg of C17H20N2O5S
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

bunazosin-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Bunazosin Hydrochloride
  ja: ブナゾシン塩酸塩
monograph id: JP18-bunazosin-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C19H27N5O3.HCl
molecular weight: 409.91
appearance:
  en: Bunazosin Hydrochloride occurs as a white crystalline powder. It is very soluble in formic acid, slightly soluble in water and in methanol, very slightly soluble in ethanol (99.5), and practically insoluble in diethyl ether. Melting point: about 2739C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.1 g of Bunazosin Hydrochlo-ride in 10 mL of 0.2 mol/L hydrochloric acid TS, and boil for 3 minutes over a flame: butylic acid like odor is percepti-ble. Determine the infrared absorption spectrum of Bunazosin Hydrochloride, previously dried, as directed in the potassium bromide disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Bunazosin Hydrochloride (1 in 100) re-sponds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Bunazosin Hydrochloride according to Method 4, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 0.05 g of Bunazosin Hydrochloride in 50 mL of the mobile phase, and use this solution as the sample solution. To exactly 1 mL of the sam-ple solution add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography 500 mL of acetonitrile and water to make 1000 mL. Flow rate: Adjust so that the retention time of bunazosin is about 5 minutes. Selection of column: Proceed with 20 mL of a mixture of the standard solution and a solution of procaine hydrochlo-ride in the mobile phase (1 in 20,000) (1:1) under the above operating conditions, and calculate the resolution. Use a column giving elution of procaine and bunazosin in this order with the resolution between these peaks being not less than 3.0. Detection sensitivity: Adjust the detection sensitivity so that the peak height of bunazosin obtained from 20 mL of the standard solution is 20 to 60z of the full-scale. Time span of measurement: About 6 times of the retention time of bunazosin. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Bunazosin Hydro-chloride, previously dried, dissolve in 6 mL of formic acid, add exactly 15 mL of 0.1 mol/L perchloric acid, and heat for 20 minutes on a water bath. After cooling, add 20 mL of acetic acid (100), and titrate <2.50> the excess perchloric acid with 0.1 mol/L sodium acetate VS (potentiometric titration). Perform a blank determination in the same manner. Each mL of 0.1 mol/L perchloric acid VS ＝ 40.99 mg of C19H27N5O3.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

bupivacaine-hydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Bupivacaine Hydrochloride Hydrate
  ja: ブピバカイン塩酸塩水和物
monograph id: JP18-bupivacaine-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C18H28N2O.HCl.H2O
molecular weight: 342.9
cas number: 14252-80-3
definition:
  en: Bupivacaine Hydrochloride Hydrate contains not less than 98.
appearance:
  en: Bupivacaine Hydrochloride Hydrate occurs as a white crystalline powder. It is freely soluble in acetic acid (100), and soluble in water, in methanol and in ethanol (99.5). It dissolves in 0.01 mol/L hydrochloric acid TS. A solution of 0.5 g of Bupivacaine Hydrochloride Hydrate in 50 mL of a mixture of ethanol (99.5), water and 5 mol/L sodium hydroxide TS (34:15:1) shows no optical rotation. Melting point: about 2529C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Bupivacaine Hydrochloride Hydrate in 0.01 mol/L hydrochloric acid TS (1 in 2000) as directed under Ul- ‌578 traviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bupivacaine Hydrochloride Hydrate as directed in the potas-sium chloride disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. A solution of Bupivacaine Hydrochloride Hydrate (1 in 50) responds to Qualitative Tests <1.09> for chloride. pH <2.54> The pH of a solution obtained by dissolving 1.0 g of Bupivacaine Hydrochloride Hydrate in 100 mL of freshly boiled and cooled water is between 4.5 to 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Bupivacaine Hydrochloride Hydrate in 50 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Bupivacaine Hydrochloride Hydrate according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). 2,6-Dimethylaniline—Dissolve exactly 0.50 g of Bupivacaine Hydrochloride Hydrate in 10 mL of methanol. To 2 mL of this solution add 1 mL of a freshly prepared solution of 4-dimethylaminobenzaldehyde in methanol (1 in 100) and 2 mL of acetic acid (100), and allow to stand for 10 minutes: the color of the solution is not more colored than the following control solution. Control solution: Prepare by proceeding in the same man-ner as above, using 2 mL of a solution of 2,6-dimethylaniline in methanol (1 in 200,000). Related substances—Dissolve 50 mg of Bupivacaine Hydrochloride Hydrate in 2.5 mL of water, add 2.5 mL of 2 mol/L sodium hydroxide TS and 5 mL of the internal stand-ard solution, shake, collect the lower layer, filter, and use the filtrate as the sample solution. Pipet 1 mL of the sample solution, and add the internal standard solution to make ex-actly 100 mL. Pipet 1 mL of this solution, add the internal standard solution to make exactly 10 mL, and use this solu-tion as the standard solution. Perform the test with 1 mL each of the sample solution and standard solution as directed under Gas Chromatography <2.02> according to the follow-ing conditions, and determine each peak area by the auto-matic integration method: the ratio of the area of the peak other than bupivacaine to the peak area of the internal standard obtained from the sample solution is not larger than the ratio of the peak area of bupivacaine to that of the internal standard from the standard solution. Internal standard solution—A solution of methyl behenate in dichloromethane (1 in 20,000). Operating conditions— Detector: A hydrogen flame-ionizati…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Bupivacaine Hydro-chloride Hydrate, dissolve in 20 mL of acetic acid (100), add 50 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 32.49 mg of C18H28N2O.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

bupranolol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Bupranolol Hydrochloride
  ja: ブプラノロール塩酸塩
monograph id: JP18-bupranolol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C14H22ClNO2.HCl
molecular weight: 308.24
definition:
  en: Bupranolol Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Bupranolol Hydrochloride occurs as a white crystalline powder. It is sparingly soluble in methanol, slightly soluble in water, in ethanol (95) and in acetic acid (100), very slightly soluble in acetic anhydride, and practically insoluble in diethyl ether. The pH of a solution of 1.0 g of Bupranolol Hydrochlo-ride in 1000 mL of water is between 5.2 and 6.2.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Take 0.01 g of Bupranolol Hydrochlo-ride in a test tube, mix with 25 mg of potassium iodide and 25 mg of oxalic acid dihydrate, cover the mouth of the test tube with filter paper moistened with a solution of 2,6-dibromo-N-chloro-1,4-benzoquinone monoimine in ethanol (95) (1 in 100), and heat gently for several minutes. Expose the filter paper to ammonia gas: the filter paper acquires a blue color. Determine the absorption spectrum of a solution of ‌JP XVIII Official Monographs / Buprenorphine Hydrochloride 579 Bupranolol Hydrochloride in 0.1 mol/L hydrochloric acid TS (1 in 10,000) as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Bupranolol Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Bupranolol Hydrochloride (1 in 200) responds to Qualitative Tests <1.09> for chloride. 1 cm Absorbance <2.24> E 1z (275 nm): 57 – 60 (after drying, 50 mg, 0.1 mol/L hydrochloric acid TS, 500 mL).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.10 g of Bupranolol Hydrochloride in 15 mL of water: the solu-tion is clear and colorless. Acidity—Dissolve 0.10 g of Bupranolol Hydrochlo-ride in 15 mL of freshly boiled and cooled water, and add 1 drop of methyl red TS: a light red color develops. To this so-lution add 0.05 mL of 0.01 mol/L sodium hydroxide VS: the color changes to yellow. Sulfate <1.14>—Perform the test with 0.10 g of Bupranolol Hydrochloride. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.168z). Heavy metals <1.07>—Proceed with 1.0 g of Bupranolol Hydrochloride according to Method 4, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Bupranolol Hydrochloride according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.30 g of Bupranolol Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solu-tion on a plate of polyamide with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of methanol, ammonia solution (28) and water (16:4:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solu-tion are not more intense than the spot from the standard so-lution. Loss on drying <2.41> Not more than 0.5z (0.5 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.18 g of Bupranolol Hy-drochloride, previously dried, dissolve in 60 mL of a mixture of acetic anhydride and acetic acid (100) (2:1) by warming, cool, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 30.82 mg of C14H22ClNO2.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

buprenorphine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Buprenorphine Hydrochloride
  ja: ブプレノルフィン塩酸塩
monograph id: JP18-buprenorphine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C29H41NO4.HCl
molecular weight: 504.1
cas number: 53152-21-9
appearance:
  en: Buprenorphine Hydrochloride occurs as white to yellowish white, crystals or a crystalline powder. It is freely soluble in methanol and in acetic acid (100), and sparingly soluble in water and in ethanol (99.5). Melting point: about 2689C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Buprenorphine Hydrochloride (1 in 5000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Buprenorphine Hydrochloride as directed in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Buprenorphine Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> for chloride. D Optical rotation <2.49> [a]20: －92 – －989(after drying, 0.4 g, methanol, 20 mL, 100 mm). pH <2.54> The pH of a solution prepared by dissolving 1.0 g of Buprenorphine Hydrochloride in 200 mL of water is between 4.0 and 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution ob-tained by dissolving 0.1 g of Buprenorphine Hydrochloride in 10 mL of water is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Buprenorphine Hydrochloride according to Method 4, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 0.10 g of Buprenor-phine Hydrochloride in 20 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sam-ple solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the area of each peak other than buprenorphine ob-tained from the sample solution is not larger than 1/4 times the peak area of buprenorphine obtained from the standard solution. Furthermore, the total area of the peaks other than ‌580‌ buprenorphine from the sample solution is not larger than 13/20 times the peak area of buprenorphine from the stand-ard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 288 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of methanol, ammonium acetate solution (1 in 100), and acetic acid (100) (6000:1000:1). Flow rate: Adjust so that the retention time of buprenor-phine is about 17 minutes. Time span of measurement: About 2.5 times as long as the retention time of buprenorphine, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 5 mL of the standard solution, and add the mobil…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Buprenorphine Hy-drochloride, previously dried, dissolve in 5 mL of acetic acid Identification (1) To 0.1 g of Busulfan add 10 mL of water and 5 mL of sodium hydroxide TS, dissolve by heat-ing, and use this solution as the sample solution. To 7 mL of the sample solution add 1 drop of potas-sium permanganate TS: the red-purple color of potassium permanganate TS changes from blue-purple through blue to green. Acidify 7 mL of the sample solution with dilute sul-furic acid, and add 1 drop of potassium permanganate TS: the color of potassium permanganate TS remains. (2) Determine the infrared absorption spectrum of Busulfan, previously dried, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Melting point <2.60> 115 – 1189C Purity (1) Sulfate <1.14>—To 1.0 g of Busulfan add 40 mL of water, and dissolve by heating. Cool in ice for 15 minutes, and filter. Wash the residue with 5 mL of water, combine the washings with the filtrate, and add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not more than 0.019z). (2) Heavy metals <1.07>—Proceed with 1.0 g of Busulfan according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Loss on drying <2.41> Not more than 2.0z (1 g, in vacu-um, phosphorus (V) oxide, 609C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g). Assay Weigh accurately about 0.2 g of Busulfan, add 40 mL of water, and boil gently under a reflux condenser for 30 minutes. Cool, and titrate <2.50> with 0.1 mol/L sodium hy-droxide VS (indicator: 3 drops of phenolphthalein TS). Each mL of 0.1 mol/L sodium hydroxide VS (100), add 50 mL of…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

burnt-alum
type: ChemicalDrugMonograph
pref label:
  en: Burnt Alum
  ja: 乾燥硫酸アルミニウムカリウム
monograph id: JP18-burnt-alum
publisher: JP
status: Official
version: 18
molecular formula: AlK(SO4)2
molecular weight: 258.21
appearance:
  en: Dried Aluminum Potassium Sulfate occurs as white masses or white powder. It is odorless. It has a slightly sweet, astringent taste. It is freely soluble in hot water and practically insoluble in ethanol (95). It dissolves slowly in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: A solution of Dried Aluminum Potassium Sulfate (1 in 20) responds to Qualitative Tests <1.09> for alu-minum salt, to Qualitative Tests <1.09> (1), (3) and (4) for potassium salt, and to Qualitative Tests <1.09> (1) and (3) for sulfate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Water-insoluble substances—To 2.0 g of Dried Aluminum Potassium Sulfate add 40 mL of water, shake frequently, and allow to stand for 48 hours. Collect the insoluble residue on a glass filter (G4), wash with 50 mL of water, and dry at 1059C for 2 hours: the mass of the residue is not more than 50 mg. Heavy metals <1.07>—Dissolve 0.5 g of Dried Alumi- num Potassium Sulfate in 45 mL of water, and filter, if necessary. Add 2 mL of dilute acetic acid and water to make 50 mL, and perform the test using this solution as the test so-lution. Prepare the control solution with 2.0 mL of Standard Lead Solution, 2 mL of dilute acetic acid and water to make 50 mL (not more than 40 ppm). Iron <1.10>—Prepare the test solution with 0.54 g of Dried Aluminum Potassium Sulfate according to Method 1, and perform the test according to Method A. Prepare the control solution with 2.0 mL of Standard Iron Solution (not more than 37 ppm). Arsenic <1.11>—Prepare the test solution with 0.40 g of Dried Aluminum Potassium Sulfate, according to Method 1, and perform the test (not more than 5 ppm). Loss on drying <2.41> Not more than 15.0z (2 g, 2009C, 4 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 1.2 g of Dried Aluminum Potassium Sulfate, previously dried, add 80 mL of water, and heat on a water bath with occasional shaking for 20 minutes. Cool, add water to make exactly 100 mL, and filter, if necessary. Discard the first 30 mL of the filtrate, take exactly the subsequent 20 mL of the filtrate, and add exactly 30 mL of 0.05 mol/L disodium dihydrogen ethylene-diamine tetraacetate VS and 20 mL of acetic acid-ammo-nium acetate buffer solution (pH 4.8), boil for 5 minutes, and cool. Add 55 mL of ethanol (95), and titrate <2.50> with 2 3 0.05 mol/L zinc acetate VS (indicator: 2 mL of dithizone TS), until the color of the solution changes from light dark ‌442‌ green to light red. Perform a blank determination in the same manner. Each mL of 0.05 mol/L disodium dihydrogen ethylenediamine tetraacetate VS ＝ 12.91 mg of AlK (SO4)2
storage conditions:
  en: Containers—Tight containers.

busulfan
type: ChemicalDrugMonograph
pref label:
  en: Busulfan
  ja: ブスルファン
monograph id: JP18-busulfan
publisher: JP
status: Official
version: 18
storage conditions:
  en: Containers—Well-closed contain-ers.

butenafine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Butenafine Hydrochloride
  ja: ブテナフィン塩酸塩
monograph id: JP18-butenafine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C6H14O6S2
molecular weight: 246.3
cas number: 101827-46-7
definition:
  en: Butenafine Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Busulfan occurs as a white crystalline powder. It is slightly soluble in diethyl ether, very slightly soluble in ethanol (95), and practically insoluble in water. C23H27N.HCl: 353.93 N-[4-(1,1-Dimethylethyl)benzyl]-N-methyl-1-(naphthalen-1-yl)methylamine monohydrochloride [101827-46-7] Butenafine Hydrochloride, when dried, contains not less than 99.0z and not more than 101.0z of butenafine hydrochloride (C23H27N.HCl). Description Butenafine Hydrochloride occurs as white, crystals or crystalline powder. JP XVIII Official Monographs / Butenafine Hydrochloride Cream 581 ‌It is very soluble in formic acid, freely soluble in methanol and in ethanol (99.5), and slightly soluble in water. The pH of a solution dissolved 0.20 g of Butenafine Hy-drochloride in 100 mL of water by warming and cooled is 3.0 to 4.0. Melting point: about 2149C (with decomposition). 0 – 10 60 → 20 40 → 80 10 – 60 Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz)
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Butenafine Hydrochloride in methanol (1 in 40,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Butenafine Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Butenafine Hydrochloride in dilute ethanol (1 in 200) responds to Qualitative Tests <1.09> (1) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Dissolve 2.0 g of Butenafine Hydrochloride in 20 mL of ethanol (99.5), add 2 mL of dilute acetic acid and ethanol (99.5) to make 50 mL, and perform the test using this solution as the test solution. The control solution: To 2.0 mL of Standard Lead Solution add 2 mL of dilute acetic acid, and add ethanol (99.5) to make 50 mL (not more than 10 ppm). (2) Related substances—Dissolve 30 mg of Butenafine Hydrochloride in 50 mL of a mixture of water and aceto-nitrile for liquid chromatography (3:2), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of water and acetonitrile for liquid chroma-tography (3:2) to make exactly 50 mL. Pipet 1 mL of this solution, add a mixture of water and acetonitrile for liquid chromatography (3:2) to make exactly 20 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area of both solutions by the automatic integration method: the area of the peak, having the relative retention time of about 0.16 to butenafine, obtained from the sample solution is not larger than 3/10 times the peak area of butenafine from the standard solution, and the area of the peak other than butenafine and the peak mentioned above from the sample solution is not larger than the peak area of butenafine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 217 nm). Column: A stainless steel column 3.0 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase A: Diluted 0.5 mol/L ammonium acetate TS (1 in 1000). Mobile phase B: Acetonitrile for liquid chromatography. Flowing of mobile phase: Control the gra…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Butenafine Hydro-chloride, previously dried, dissolve in 5 mL of formic acid, add 80 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 35.39 mg of C23H27N.HCl
storage conditions:
  en: Containers—Tight containers.

butropium-bromide
type: ChemicalDrugMonograph
pref label:
  en: Butropium Bromide
  ja: ブトロピウム臭化物
monograph id: JP18-butropium-bromide
publisher: JP
status: Official
version: 18
molecular formula: C28H38BrNO4
molecular weight: 532.51
cas number: 29025-14-7
definition:
  en: Butropium Bromide, when dried, contains not less than 98.
appearance:
  en: Butropium Bromide occurs as white, crystals or crystalline powder. It is very soluble in formic acid, freely soluble in metha-nol, soluble in ethanol (95), slightly soluble in water, and practically insoluble in diethyl ether and in acetic anhydride.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mg of Butropium Bromide add 3 drops of fuming nitric acid, and evaporate on a water bath to dryness. Dissolve the residue in 1 mL of N,N-dimethylfor-mamide, and add 5 to 6 drops of tetraethylammonium hy-droxide TS: a red-purple color develops. Determine the absorption spectrum of a solution of Butropium Bromide in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum 1: both spectra exhibit similar intensities of absorption at the same wavelengths. Separately, determine the absorption spectrum of a solution of Butropium Bromide in methanol (1 in 5000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spec- trum 2: both spectra exhibit similar intensities of absorption at the same wavelengths. A solution of Butropium Bromide in methanol (1 in 20) responds to Qualitative Tests <1.09> (1) for bromide. D Optical rotation <2.49> [a]20: －14.0 – －17.09(after dry-ing, 0.5 g, methanol, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Dissolve 1.0 g of Butro-pium Bromide in 40 mL of ethanol (95), add 2 mL of dilute acetic acid and water to make 50 mL. Perform the test, using this solution as the test solution. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 50 mg of Butropium ‌584 Bromide in 10 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with ex-actly 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the peak area, having the relative retention time about 0.5 to butropium obtained from the sample solution is not larger than 1/4 times the peak area from the standard solution, and the total area of all peaks other than the peak eluted first, the peak, having the relative retention time to butropium about 0.5 and butropium peak from the sample solution is not larger than the peak area from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 220 nm). Column: A stainless steel column about 5 mm in inside diameter and about 15 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 1.15 g of sodium lauryl sulfate in 1000 mL of a mixture of acetonitrile and 0.005 mol/L sulfu-ric acid (3:2). Flow rate: Adjust so that the retention time of butropium is about 5 minutes. Selection of column: Dissolve 0.50 g of Butropium Bromide in 9 mL of ethanol (99.5) and 1 mL of 0.1 mol/L potassium hydroxide-ethanol TS, and heat at 709C for 15 minutes. After cooling, to 1 mL of this solution add the …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.8 g of Butropium Bromide, previously dried, dissolve in 5 mL of formic acid, add 100 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid-dioxane VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid-dioxane VS ＝ 53.25 mg of C28H38BrNO4
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

butyl-parahydroxybenzoate
type: ChemicalDrugMonograph
pref label:
  en: Butyl Parahydroxybenzoate
  ja: パラオキシ安息香酸ブチル
monograph id: JP18-butyl-parahydroxybenzoate
publisher: JP
status: Official
version: 18
molecular formula: C11H14O3
molecular weight: 194.23
definition:
  en: Butyl Parahydroxybenzoate contains not less than 98.
appearance:
  en: Butyl Parahydroxybenzoate occurs as color-less crystals or white crystalline powder. It is very soluble in methanol, freely soluble in ethanol (95) and in acetone, and practically insoluble in water.◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Butyl Parahydroxybenzoate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Butyl Parahydroxybenzoate RS: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Butyl Parahydroxybenzoate in ethanol (95) to make 10 mL: the solution is clear and not more intensely colored than the following control solution. Control solution: To 5.0 mL of Cobalt (II) Chloride CS, 12.0 mL of Iron (III) Chloride CS and 2.0 mL of Copper (II) Sulfate CS add diluted dilute hydrochloric acid (1 in 10) to make 1000 mL. Acidity—To 2 mL of the solution of Butyl Parahy-droxybenzoate obtained in (1) add 3 mL of ethanol (95), add 5 mL of freshly boiled and cooled water and 0.1 mL of bromocresol green-sodium hydroxide-ethanol TS, then add 0.1 mol/L sodium hydroxide VS until the solution shows a blue color: the volume of 0.1 mol/L sodium hydroxide VS used does not exceed 0.1 mL. (3) Heavy metals <1.07>—Dissolve 1.0 g of Butyl Par- ahydroxybenzoate in 25 mL of acetone, add 2 mL of dilute acetic acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of Standard Lead Solution add 25 mL of acetone, 2 mL of dilute acetic acid, and water to make 50 mL (not more than 20 ppm).◆ Related substances—Dissolve 50.0 mg of Butyl Par-ahydroxybenzoate in 2.5 mL of methanol, and add the mobile phase to make exactly 50 mL. Pipet 10 mL of this so-lution, add the mobile phase to make exactly 100 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add the mobile phase to make exactly ‌JP XVIII Official Monographs / Cabergoline 585‌ 20 mL. Pipet 1 mL of this solution, add the mobile phase to make exactly 10 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the peak area of parahydroxybenzoic acid having a relative retention time of about 0.1 to butyl parahy-droxyben…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 50.0 mg each of Butyl Par-ahydroxybenzoate and Butyl Parahydroxybenzoate RS, dis-solve separately in 2.5 mL each of methanol, and add the mobile phase to make exactly 50 mL. Pipet 10 mL each of these solutions, add the mobile phase to make exactly 100 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of butyl parahydroxybenzoate in each solution. Mobile phase: A mixture of methanol and potassium dihy-drogen phosphate solution (17 in 2500) (1:1). Flow rate: 1.3 mL per minute. System suitability— System performance: Dissolve 5 mg each of Butyl Parahy-droxybenzoate, propyl parahydroxybenzoate and parahy-droxybenzoic acid in the mobile phase to make exactly 100 mL. Pipet 1 mL of this solution, add the mobile phase to make exactly 10 mL, and use this solution as the solution for system suitability test (1). Separately, dissolve 5 mg of isobutyl parahydroxybenzoate in the mobile phase to make exactly 100 mL. Pipet 0.5 mL of this solution, add the stand-ard solution to make exactly 50 mL, and use this solution as the solution for system suitability test (2). When the proce-dure is run with 10 mL each of the solution for system suita-bility test (1) and (2) under the above operating conditions, parahydroxybenzoic acid, propyl parahydroxybenzoate, isobutyl parahydroxybenzoate and butyl parahydroxybenzo-ate are eluted in this order, the relative retention times of parahydroxybenzoic acid, propyl parahydroxybenzoate and isobutyl parahydoxybenzoate to butyl parahydroxybenzoate are about 0.1, about 0.5 and about 0.9, respectively, the resolution between the peaks of propyl parahydroxybenzoate and butyl parahydroxybenzoate is not less than 5.0, and the resolution between the peaks of isobutyl parahydroxyben…
storage conditions:
  en: Containers—Well-closed contain-ers.◆
type: PharmacopoeiaMonograph

byakkokaninjinto-extract
type: ChemicalDrugMonograph
pref label:
  en: Byakkokaninjinto Extract
  ja: 白虎加人参湯エキス
monograph id: JP18-byakkokaninjinto-extract
publisher: JP
status: Official
version: 18
definition:
  en: Byakkokaninjinto Extract contains not less than 9 mg and not more than 36 mg of mangiferin, not less than 13 mg and not more than 39 mg of glycyrrhizic acid (C42H62O16: 822.
appearance:
  en: Byakkokaninjinto Extract occurs as a very pale yellow-brown to light brown powder or blackish brown viscous extract. It has a slight odor, and has a slightly sweet and slightly bitter taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2.0 g of the dry extract (or 6.0 g of the viscous extract) add 10 mL of sodium hydroxide TS, shake, then add 5 mL of 1-butanol, shake, centrifuge, and use the 1-butanol layer as the sample solution. Separately, to 1 g of pulverized Anemarrhena Rhizome add 10 mL of water, shake, then add 10 mL of 1-butanol, shake, centri-fuge, and use the 1-butanol layer as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL of the sample solu-tion and 1 mL of the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, 1-propanol, water and acetic acid (100) (7:5:4:1) to a distance of about 7 cm, and air-dry the plate. Spray evenly 4-dimethylaminobenzaldehyde TS for spraying on the plate, and heat the plate at 1059C for 2 minutes, and allow to cool: one of the several spots obtained from the sample solution has the same color tone and Rf value with the yellowish red to dark red spot (at an Rf value of about 0.3) from the standard solution (Anemarrhena Rhizome). Place 2.0 g of the dry extract (or 6.0 g of the viscous extract) in a porcelain crucible, and ignite to incinerate at 500 – 5509C. To the residue add 60 mL of water, shake, cen-trifuge, and use the supernatant as the sample solution. Add ammonium oxalate TS to the sample solution: a white pre-cipitate is formed. The precipitate does not dissolve in diluted acetic acid, but dissolves on the addition of diluted hydrochloric acid (Gypsum). To 1.0 g of the dry extract (or 3.0 g of the viscous ex-tract) add 10 mL of water, shake, then add 10 mL of 1-butanol, shake, centrifuge, and use the 1-butanol layer as the sample solution. Separately, dissolve 1 mg of liquiritin for thin-layer chromatography in 1 mL of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 1 mL each of the sample solut…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Prepare the test solution with 1.0 g of the dry extract (or an amount of the viscous ex-tract, equivalent to 1.0 g of the dried substance) as directed under Extracts (4), and perform the test (not more than 30 ppm). (2) Arsenic <1.11>—Prepare the test solution with 0.67 g of the dry extract (or an amount of the viscous extract, equivalent to 0.67 g of the dried substance) according to Method 3, and perform the test (not more than 3 ppm). Loss on drying <2.41> The dry extract: Not more than 10.0z (1 g, 1059C, 5 hours). The viscous extract: Not more than 66.7z (1 g, 1059C, 5 hours). Total ash <5.01> Not more than 20.0z, calculated on the dried basis.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Mangiferin—Weigh accurately about 0.5 g of the dry extract (or an amount of the viscous extract, equiva-lent to about 0.5 g of the dried substance), add exactly 50 mL of diluted methanol (1 in 2), shake for 15 minutes, cen-trifuge, and use the supernatant as the sample solution. Separately, weigh accurately about 10 mg of mangiferin for assay, dissolve in diluted methanol (1 in 2) to make exactly 200 mL, and use this solution as the standard solution. Per-form the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and de-termine the peak areas, AT and AS, of mangiferin in each so-lution. Amount (mg) of mangiferin ＝ MS × AT/AS × 1/4 MS: Amount (mg) of mangiferin for assay taken, calcu-lated on the basis of the content obtained by qNMR JP XVIII Crude Drugs and Related Drugs / Byakkokaninjinto Extract 1971 Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 367 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of water, acetonitrile and phos-phoric acid (1780:220:1). Flow rate: 1.0 mL per minute. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of mangiferin are not less than 5000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of mangiferin is not more than 1.5z. Glycyrrhizic acid—Weigh accurately about 0.5 g of the dry extract (or an amount of the viscous extract, equiva-lent to about 0.5 g…
storage conditions:
  en: Containers—Tight containers.

cabergoline
type: ChemicalDrugMonograph
pref label:
  en: Cabergoline
  ja: カベルゴリン
monograph id: JP18-cabergoline
publisher: JP
status: Official
version: 18
molecular formula: C26H37N5O2
molecular weight: 451.6
definition:
  en: Cabergoline contains not less than 98.
appearance:
  en: Cabergoline occurs as a white crystalline pow-der. It is very soluble in methanol, freely soluble in ethanol (95), and very slightly soluble in water. It is gradually colored to yellow by light. It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cabergoline in ethanol (95) (1 in 30,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cabergoline RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. lution. Amount (mg) of cabergoline (C 26H37N5O2) ＝ M S × AT/AS (2) Determine the infrared absorption spectrum of Cabergoline as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Cabergoline RS: both spectra exhibit similar intensi-ties of absorption at the same wave numbers. If any differ-ence appears between the spectra, dissolve Cabergoline and Cabergoline RS in ethanol (95), respectively, then evaporate the ethanol, dry the residues, and repeat the test on the residues. D Optical rotation<<2.49> [a]20: －77 – －839(0.1 g calculated on the anhydrous basis, ethanol (95), 50 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Cabergoline according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Conduct this procedure using light-resistant vessels. Perform the test with 20 mL of the sample solution obtained in the Assay as directed under Liq-uid Chromatography <2.01> according to the following con-ditions. Determine each peak area by the automatic integra-tion method, and calculate the amounts of them by the area percentage method: the amount of related substances A and B, having the relative retention times of about 0.8 and about 2.8 to cabergoline are not more than 0.5z, respectively, and the amount of the peak other than cabergoline and the peaks mentioned above is not more than 0.1z. Furthermore, the total amount of the peaks other than cabergoline is not more than 1.5z. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 4 times as long as the retention time of cabergoline, beginning after the solvent peak. System suitability— System performance: Proceed as directed in the system suitability in the Assay. Test for required detectability: Use the diluted sample so-lution (1 in 500) as the solution for system suitability test. Pipet 5 mL of the solution for system suitability test, and add the mobile phase to make exactly 20 mL. Confirm that the peak area of cabergoline obtained with 20 mL of this so-lution is equivalent to 18 to 32z of that with 20 mL of the solution for system suitability test. System repeatability: When the test is repeated 6 times with 20 mL of the solution for system suitability test under the above operating conditions, the relative standard devia-tion of the peak area of cabergoline is not more than 2.0z. Water <2.48> Not more than 0.5z (1 g, volumetric titra-tion, direct titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Conduct this procedure using light-resistant vessels. Weigh accurately about 30 mg each of Cabergoline and Cabergoline RS (separately determine the water <2.48> in the same manner as Cabergoline), dissolve each in the mobile phase to make exactly 25 mL, and use these solutions as the sample solution and the standard solution, respectively. Per-form the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and de-termine the peak areas, AT and AS, of cabergoline in each so- MS: Amount (mg) of Cabergoline RS taken, calculated on the anhydrous basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column 4.0 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 6.8 g of potassium dihydrogen phosphate in 900 mL of water, adjust to pH 2.0 with phos-phoric acid, and add water to make 1000 mL. To this solu-tion add 0.2 mL of triethylamine. To 840 mL of this solution add 160 mL of acetonitrile. Flow rate: Adjust so that the retention time of cabergoline is about 12 minutes. System suitability— System performance: Suspend 50 mg of Cabergoline in 10 mL of 0.1 mol/L sodium hydroxide TS, and stir for 15 minutes. To 1 mL of this solution add 1 mL of 0.1 mol/L hydrochloric acid TS, and add the mobile phase to make 10 mL. When the procedure is run with 20 mL of this solution under the above operating conditions, the resolution be-tween the peaks of related substance A having the relative retention time of about 0.8 to cabergoline and cabergoline is not less than 3. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area …
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cadralazine
type: ChemicalDrugMonograph
pref label:
  en: Cadralazine
  ja: ‌カドララジン
monograph id: JP18-cadralazine
publisher: JP
status: Official
version: 18
molecular formula: C12H21N5O3
molecular weight: 283.33
cas number: 64241-34-5
definition:
  en: Cadralazine, when dried, contains not less than 98.
appearance:
  en: Cadralazine occurs as a pale yellow to light yellow crystalline powder. It is freely soluble in acetic acid (100), soluble in methanol, sparingly soluble in ethanol (99.5), and slightly soluble in water. It dissolves in 0.05 mol/L sulfuric acid TS. A solution of Cadralazine in methanol (1 in 40) shows no optical rotation. Melting point: about 1659C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cadralazine in 0.05 mol/L sulfuric acid TS (1 in 125,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Cadralazine, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 0.40 g of Cadrala-zine in 15 mL of methanol, add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solu-tion as the test solution. Prepare the control solution with 0.40 mL of 0.01 mol/L hydrochloric acid VS by adding 15 mL of methanol, 6 mL of dilute nitric acid, and water to make 50 mL (not more than 0.036z). Heavy metals <1.07>—Proceed with 1.0 g of Cadrala- zine according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 50 mg of Cadralazine in 20 mL of 0.05 mol/L sulfuric acid TS, add water to 100 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the area of the peak, having the relative retention time of about 2.1 to cadralazine, obtained from the sample solution is not larger than the peak area of cadralazine from the standard solution, and the area of the peak other than cadralazine and the peak mentioned above is not larger than 2/5 times the peak area of cadralazine from the standard solution. Furthermore, the total area of the peaks other than cadralazine from the sample solution is not larger than 2 times the peak area of cadralazine from the standard solu-tion. For the areas of the peaks, having the relative retention time of about 0.49 and about 2.1 to cadralazine, multiply their correction factors, 0.65 and 1.25, respectively. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 250 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized si…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Cadralazine, previ-ously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 28.33 mg of C12H21N5O3
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

caffeine-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Caffeine Hydrate
  ja: カフェイン水和物
monograph id: JP18-caffeine-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C8H10N4O2.H2O
molecular weight: 212.21
cas number: 5743-12-4
definition:
  en: Caffeine Hydrate, when dried, contains not less than 98.
appearance:
  en: Caffeine Hydrate occurs as white, soft crystals or powder. It is odorless, and has a slightly bitter taste. It is freely soluble in chloroform, sparingly soluble in water, in acetic acid (100) and in acetic anhydride, slightly soluble in ethanol (95), and very slightly soluble in diethyl ether. The pH of a solution of 1.0 g of Caffeine Hydrate in 100 mL of water is between 5.5 and 6.5. It effloresces in dry air.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2 mL of a solution of Caffeine Hy-drate (1 in 500) add tannic acid TS dropwise: a white precipi-tate, which dissolves upon the dropwise addition of tannic acid TS, is produced. To 0.01 g of Caffeine Hydrate add 10 drops of hydrogen peroxide TS and 1 drop of hydrochloric acid, and evaporate to dryness on a water bath: the residue acquires a yellow-red color. Invert the residue over a vessel containing 2 to 3 drops of ammonia TS: the color turns red-purple, and disappears upon the addition of 2 to 3 drops of sodium hy-droxide TS. Dissolve 0.01 g of Caffeine Hydrate in water to make 50 mL. To 5 mL of this solution add 3 mL of diluted acetic acid (31) (3 in 100) and 5 mL of a solution of pyridine (1 in 10), mix, add 2 mL of diluted sodium hypochlorite TS (1 in 5), and allow to stand for 1 minute. Add 2 mL of sodium thiosulfate TS and 5 mL of sodium hydroxide TS to the solu-tion: a yellow color develops.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 2.0 g of Caffeine Hydrate in 80 mL of hot water, cool rapidly to 209C, add water to make 100 mL, and use this solution as the sample solution. To 40 mL of the sample solution add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.25 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.011z). Sulfate <1.14>—To 40 mL of the sample solution ob- tained in (1) add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not more than 0.024z). Heavy metals <1.07>—Proceed with 2.0 g of Caffeine Hydrate according to Method 2, and perform the test. Pre- ‌590 pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 10 ppm). Related substances—Dissolve 0.10 g of Caffeine Hy-drate in 10 mL of chloroform, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add chloroform to make exactly 100 mL. Pipet 1 mL of this solu-tion, add chloroform to make exactly 10 mL, and use this solution as the standard solution. Perform the test as di-rected under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chroma-tography. Develop the plate with a mixture of chloroform and ethanol (95) (9:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wave-length: 254 nm): the spots other than the principal spot ob-tained from the sample solution are not more intense than the spot from the standard solution. Readily carbonizable substances <1.15>—Perform the test using 0.5 g of Caffeine Hydrate: the solution is not more colored than Matching Fluid D. Loss on drying <2.41> 0.5 – 8.5z (1 g, 809C, 4 hours). Residue on ignition <2.44> Not more t…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Caffeine Hydrate, previously dried, dissolve in 70 mL of a mixture of acetic an-hydride and acetic acid (100) (6:1), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the solution changes from purple through green to yellow (indicator: 3 drops of crystal violet TS). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 19.42 mg of C8H10N4O2
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

calcitonin-salmon
type: ChemicalDrugMonograph
pref label:
  en: Calcitonin Salmon
  ja: カルシトニン サケ
monograph id: JP18-calcitonin-salmon
publisher: JP
status: Official
version: 18
molecular formula: S2
molecular weight: 3431.85
cas number: 47931-85-1
definition:
  en: Calcitonin Salmon is synthetic salmon calcitonin, and is a peptide consisting of 32 amino acid residues. It contains not less than 4000 Units of calcitonin salmon per 1 mg of peptide.
appearance:
  en: Calcitonin Salmon occurs as a white powder. It is freely soluble in water. It dissolves in dilute acetic acid. Dissolve 20 mg of Calcitonin Salmon in 2 mL of water: the pH of the solution is between 5.0 and 7.0. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Dissolve 1 mg of Calcitonin Salmon in 1 mL of dilute acetic acid. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. ture of about 1309C. Color developing time: About 1 minute. Mobile phase: Prepare mobile phases A, B, C, D and E according to the following table. 1 cm Absorbance <2.24> E1z (275 nm): 3.3 – 4.0 (1 mg, dilute acetic acid, 1 mL). Mobile phase A Mobile phase B Mobile phase C Mobile phase D Mobile phase E Citric acid monohydrate 19.80 g 22.00 g 12.80 g 6.10 g — Trisodium citrate 6.19 g dihydrate 7.74 g 13.31 g 26.67 g — Sodium hydroxide — — — — 8.00 g Sodium chlo- ride 5.66 g 7.07 g 3.74 g 54.35 g — Ethanol (99.5) 130.0 mL 20.0 mL 4.0 mL — 100.0 mL Benzyl alcohol — — — 5.0 mL — Thiodiglycol 5.0 mL 5.0 mL 5.0 mL — — Peptide content (z) ＝ 3431.85 × 5/M × A/11 × 100 A: Total (mmol/mL) of the amino acid analysis values of valine, leucine, glycine and proline M: Amount (mg) of Calcitonin Salmon taken 11: Total of the theoretical residue numbers of valine, leu-cine, glycine and proline per one mole of calcitonin salmon
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acetic acid—Weigh accurately about 10 mg of Calcitonin Salmon, dissolve in water to make exactly 10 mL, and use this solution as the sample solution. Separately, weigh accurately about 1 g of acetic acid (100), and dissolve in water to make exactly 100 mL. Pipet 2 mL of this solu- Lauromacrogol solution (1 in 4) 4.0 mL 4.0 mL 4.0 mL 4.0 mL 4.0 mL tion, add water to make exactly 200 mL, and use this solu-tion as the standard solution. Perform the test with exactly Caprylic acid 0.1 mL 0.1 mL 0.1 mL 0.1 mL 0.1 mL Water a sufficient a sufficient a sufficient a sufficient a sufficient amount amount amount amount amount Total volume 1000 mL 1000 mL 1000 mL 1000 mL 1000 mL Flowing of mobile phase: Control the gradient by mixing the mobile phases A, B, C, D and E as directed in the follow-ing table. Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) Mobile phase C (volz) Mobile phase D (volz) Mobile phase E (volz) 0 – 1.5 1.5 – 4 4 – 12 12 – 26 26 – 30 Reaction reagent: Mix 407 g of lithium acetate dihydrate, 245 mL of acetic acid (100) and 801 mL of 1-methoxy-2-propanol, add water to make 2000 mL, stir for 10 minutes while passing nitrogen, and use this solution as solution A. Separately, to 1957 mL of 1-methoxy-2-propanol add 77 g of ninhydrin and 0.134 g of sodium borohydride, stir for 30 minutes while passing nitrogen, and use this solution as solu- 100 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine the peak areas, AT and AS, of acetic acid in each solution, and calculate the amount of acetic acid by the following equation: the amount of acetic acid is not more than 7.0z. Amount (z) of acetic acid (CH3COOH) ＝ MS/MT × AT/AS × 1/10 MS: Amount (mg) of acetic acid (100) taken MT: Amount (mg) of Calcitonin Salmon taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm). Column: A stainless steel colum…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (i) Test animals: Select healthy albino rats weigh-ing between 55 and 180 g, fasted for 24 hours before the test but allowed to drink water ad libitum. Standard solutions: Dissolve a quantity of Calcitonin Salmon RS in acetic acid buffer solution containing 0.1z bovine serum albumin, and prepare a high-dose standard solution SH and a low-dose standard solution SL containing exactly 0.050 and 0.025 Units per mL, respectively. Sample solutions: According to the labeled units, Ya ＝ －Y1 － Y2 ＋ Y3 ＋ Y4 Yb ＝ Y1 － Y2 ＋ Y3 － Y4 a: Amount (mg) of Calcitonin Salmon taken b: Total volume (mL) of the high-dose sample solution prepared by dissolving Calcitonin Salmon in acetic acid buffer solution containing 0.1z bovine serum albumin. c: Peptide content (z) F? computed by the following equation should be smaller than F1 shown in the table against n with which s2 is calcu-lated. Calculate L (P ＝ 0.95) by use of the following equa-tion: L should be not more than 0.20. If F? exceeds F1, or if L exceeds 0.20, repeat the test, increasing the number of animals or arranging the assay conditions so that F? is not more than F1 and L is not more than 0.20. F? ＝ (－Y1 ＋ Y2 ＋ Y3 － Y4)2/4fs2 f: Number of the test animals of each group. s 2 ＝ {Sy2 － (Y/f )}/n Sy2: The sum of squares of y1, y2, y3 and y4 in each group. Y ＝ Y 2 ＋ Y2 ＋ Y 2 ＋ Y 2 1 2 3 4 weigh accurately a suitable amount of Calcitonin Salmon, and dissolve in acetic acid buffer solution containing 0.1z bovine serum albumin, and prepare a high-dose sample solu- n ＝ 4( f － 1) (C － 1)(CM 2 ＋ 0.09062) L ＝ 2 C ＝ Y 2/(Y 2 － 4fs2t2) b b tion TH and the low-dose sample solution TL having Units equal to the standard solutions in equal volumes, respec-tively. Dose for injection: Inject 0.3 mL per animal. Procedure: Divide the test animals at random into 4 groups, A, B, C and D, with not less than 8 animals and equal numbers in each group. Inject SH, SL, TH and TL into the tail vein or subcutaneously into the neck of each animal of the respe…
storage conditions:
  en: Containers—Hermetic containers.
type: PharmacopoeiaMonograph

camostat-mesilate
type: ChemicalDrugMonograph
pref label:
  en: Camostat Mesilate
  ja: カモスタットメシル酸塩
monograph id: JP18-camostat-mesilate
publisher: JP
status: Official
version: 18
molecular formula: C20H22N4O5.CH4O3S
molecular weight: 494.52
cas number: 59721-29-8
definition:
  en: Camostat Mesilate, when dried, contains not less than 98.
appearance:
  en: Camostat Mesilate occurs as white, crystals or QT and QS, of the peak area of camostat to that of the inter-nal standard. Amount (mg) of camostat mesilate (C20H22N4O5.CH4O3S) ＝ MS × QT/QS MS: Amount (mg) of Camostat Mesilate RS taken Internal standard solution—A solution of butyl parahy-droxybenzoate in ethanol (95) (1 in 1500). ‌JP XVIII Official Monographs / dl-Camphor 611 Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 265 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). ‌Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of methanol, a solution of so-dium 1-heptane sulfonate (1 in 500), a solution of sodium lauryl sulfate (1 in 1000) and acetic acid (100) (200:100:50:1). Flow rate: Adjust so that the retention time of camostat is about 10 minutes. System suitability— System performance: When the procedure is run with 2 mL of the standard solution under the above operating condi-tions, camostat and the internal standard are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeated 6 times with 2 mL of the standard solution under the above operating conditions, the relative standard deviation of the ratio of the peak area of camostat to that of the internal standard is not more than 1.0z.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 4 mL of a solution of Camostat Mesilate (1 in 2000) add 2 mL of 1-naphthol TS and 1 mL of diacetyl TS, and allow to stand for 10 minutes: a red color develops. Determine the absorption spectrum of a solution of Camostat Mesilate (1 in 100,000) as directed under Ultravio-let-visible Spectrophotometry <2.24>, and compare the spec-trum with the Reference Spectrum or the spectrum of a solu-tion of Camostat Mesilate RS prepared in the same manner as the sample solution: both spectra exhibit similar intensi-ties of absorption at the same wavelengths. A 0.1 g portion of Camostat Mesilate responds to Qualitative Tests <1.09> (1) for mesilate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Dissolve 1.0 g of Camostat Mesilate in 40 mL of water by warming, and add 2 mL of dilute acetic acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 2.0 mL of Standard Lead Solution and 2 mL of dilute acetic acid (not more than 20 ppm). Arsenic <1.11>—Dissolve 2.0 g of Camostat Mesilate in 20 mL of 2 mol/L hydrochloric acid TS by heating in a water bath, and continue to heat for 20 minutes. After cool-ing, centrifuge, take 10 mL of the supernatant liquid, and use this solution as the test solution. Perform the test (not more than 2 ppm). Related substances—Dissolve 30 mg of Camostat Mesilate in 10 mL of ethanol (95), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add ethanol (95) to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and air-dry the plate. Allow the plate to stand overnight in iodine vapor: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 1.0z (1 g, silica gel, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 50 mg each of Camostat Mesilate and Camostat Mesilate RS, previously dried, and dissolve each in water to make exactly 50 mL. Pipet 5 mL each of these solutions, add exactly 5 mL of the internal standard solution, and use these solutions as the sample so-lution and the standard solution, respectively. Perform the test with 2 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac- cording to the following conditions, and calculate the ratios, Dimethylcarbamoylmethyl 4-(4-guanidinobenzoyloxy)phenylacetate monomethanesulfonate [59721-29-8] Camostat Mesilate, when dried, contains not less than 98.5z of camostat mesilate (C20H22N4O5. CH4O3S). Description Camostat Mesilate occurs as white, crystals or QT and QS, of the peak area of camostat to that of the inter-nal standard. Amount (mg) of camostat mesilate (C20H22N4O5.CH4O3S) ＝ MS × QT/QS MS: Amount (mg) of Camostat Mesilate RS taken Internal standard solution—A solution of butyl parahy-droxybenzoate in ethanol (95) (1 in 1500). ‌JP XVIII Official Monographs / dl-Camphor 611 Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 265 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). ‌Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of methanol, a solution of so-dium 1-heptane sulfonate (1 in 500), a solution of sodium lauryl sulfate (1 in 1000) and acetic acid (100) (200:100:50:1). Flow rate: Adjust so that the retention time of camostat is about 10 minutes. System suitability— System performance: When the procedure is run with 2 mL of the standard solution under the above operating condi-tions, camostat and the internal standard are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeat…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

candesartan-cilexetil
type: ChemicalDrugMonograph
pref label:
  en: Candesartan Cilexetil
  ja: カンデサルタン シレキセチル
monograph id: JP18-candesartan-cilexetil
publisher: JP
status: Official
version: 18
molecular formula: C33H34N6O6
molecular weight: 610.66
definition:
  en: Candesartan Cilexetil contains not less than 99.
appearance:
  en: Candesartan Cilexetil occurs as white, crystals or crystalline powder. It is soluble in acetic acid (100), sparingly soluble in meth-anol, slightly soluble in ethanol (99.5), and practically in-soluble in water. A solution of Candesartan Cilexetil in methanol (1 in 100) shows no optical rotation. Candesartan Cilexetil shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Candesartan Cilexetil in methanol (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Can-desartan Cilexetil as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, recrystallize the sample and the RS according to the method otherwise specified, filter and dry the crystals, and perform the test with the crystals.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Water—Shake 1.0 g of dl-Camphor with 10 mL of carbon disulfide: the solution is clear. Chlorinated compounds—Mix 0.20 g of finely pow-dered dl-Camphor with 0.4 g of sodium peroxide in a dried porcelain crucible. Heat the crucible gently by the open flame until the incineration is complete. Dissolve the residue in 20 mL of warm water, acidify with 12 mL of dilute nitric acid, and filter the solution into a Nessler tube. Wash the filter paper with three 5-mL portions of hot water, adding the washings to the filtrate. After cooling, add water to make 50 mL, then add 1 mL of silver nitrate TS, mix well, and allow to stand for 5 minutes: the turbidity of the solu-tion does not exceed that of the following control solution. Control solution: Prepare in the same manner as described above, using 0.20 mL of 0.01 mol/L hydrochloric acid VS. Non-volatile residue—Heat 2.0 g of dl-Camphor on a water bath until sublimation is complete, then dry the residue at 1059C for 3 hours: the mass of the residue does not exceed 1.0 mg.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g each of dl-Camphor and dl-Camphor RS, add exactly 5 mL each of the internal standard solution, dissolve in ethanol (99.5) to make 100 mL, and use these solutions as the sample solution and standard solution, respectively. Perform the test with 2 mL each of the sample solution and standard solution as directed under Gas Chromatography <2.02> according to the follow-ing conditions, and calculate the ratios, QT and QS, of the peak area of dl-camphor to that of the internal standard. Amount (mg) of dl-camphor (C10H16O) ＝ MS × QT/QS MS: Amount (mg) of dl-Camphor RS taken Internal standard solution—A solution of methyl salicylate in ethanol (99.5) (1 in 25). Operating conditions— Detector: A hydrogen flame-ionization detector. Column: A glass column 3 mm in inside diameter and 3 m in length, which is packed with 10z of polyethylene glycol 20 M for gas chromatography supported on 180 to 250 mm mesh silanized siliceous earth for gas chromatography. Column temperature: A constant temperature of about 1609C. Carrier gas: Nitrogen. Flow rate: Adjust so that the retention time of dl-camphor is about 6 minutes. System suitability— System performance: When the procedure is run with 2 mL of the standard solution under the above operating condi-tions, dl-camphor and the internal standard are eluted in this order with the resolution between these peaks being not less than 7. C33H34N6O6: 610.66 (1RS)-1-(Cyclohexyloxycarbonyloxy)ethyl-2-ethoxy-1-{[2?-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}- 1H-benzimidazole-7-carboxylate [145040-37-5] Candesartan Cilexetil contains not less than 99.0z and not more than 101.0z of candesartan cilexetil (C33H34N6O6), calculated on the anhydrous basis. Description Candesartan Cilexetil occurs as white, crystals or crystalline powder. It is soluble in acetic acid (100), sparingly soluble in meth-anol, slightly soluble in ethanol (99.5), and practically in-soluble in water. A solution of Candesartan Cilexetil in methanol (1 in 1…
storage conditions:
  en: Containers—Well-closed contain-ers.

capsicum-and-salicylic-acid-spirit
type: ChemicalDrugMonograph
pref label:
  en: Capsicum and Salicylic Acid Spirit
  ja: トウガラシ・サリチル酸精
monograph id: JP18-capsicum-and-salicylic-acid-spirit
publisher: JP
status: Official
version: 18
appearance:
  en: Capsicum and Salicylic Acid Spirit is a light brown-yellow liquid. Specific gravity d 20: about 0.84
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Shake 10 mL of Capsicum and Salicylic Acid Spirit with 15 mL of sodium hydrogen carbonate TS and 10 mL of diethyl ether, and separate the aqueous layer. To 1 mL of the solution add hydrochloric acid-potassium chloride buffer solution (pH 2.0) to make 200 mL, and to 5 mL of this solution add 5 mL of a solution of iron (III) ni-trate enneahydrate (1 in 200): a red-purple color is produced (salicylic acid). To 0.5 mL of Capsicum and Salicylic Acid Spirit add 20 mL of water and 5 mL of dilute hydrochloric acid, extract with 20 mL of diethyl ether, wash the diethyl ether extract with two 5-mL portions of sodium hydrogen carbonate TS, and then extract with 20 mL of dilute sodium hydroxide TS. To 1 mL of the extract add 1 mL of sodium nitrite TS and 1 mL of dilute hydrochloric acid, shake, and allow to stand for 10 minutes. Add 3 mL of sodium hydroxide TS: a yellow color is produced (phenol). To 0.2 mL of Capsicum and Salicylic Acid Spirit add 5 mL of dilute hydrochloric acid, extract with 5 mL of chlo-roform, and use the extract as the sample solution. Dissolve 0.01 g of salicylic acid and 0.02 g of phenol in 5 mL and 25 mL of chloroform, respectively, and use both solutions as the standard solution (1) and the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL of the sample solu-tion and standard solutions (1) and (2) on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform, acetone and acetic acid (100) (45:5:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): two spots of the several spots obtained from the sample solution exhibit the same Rf values as those from standard solution (1) and standard solution (2). Spray evenly iron (III) chloride TS upon the plate: one of the sever-al spots from the sample solution has the same color tone and Rf value with the spo…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

capsicum-tincture
type: ChemicalDrugMonograph
pref label:
  en: Capsicum Tincture
  ja: トウガラシチンキ
monograph id: JP18-capsicum-tincture
publisher: JP
status: Official
version: 18
definition:
  en: Capsicum Tincture contains not less than 0.
appearance:
  en: Capsicum Tincture is a yellow-red liquid. It has a burning, pungent taste. Specific gravity d 20: about 0.82
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Proceed as directed in the Identification under Capsicum, using Capsicum Tincture as the sample solution. Spot 20 mL each of the sample solution and stand-ard solution. Alcohol number <1.01> Not less than 9.7 (Method 2).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Pipet 2 mL of Capsicum Tincture, add methanol to make exactly 20 mL, and use this solution as the sample solution. Separately, weigh accurately about 10 mg of (E)-capsaicin for assay, previously dried in a desiccator (in vacu-um, phosphorus (V) oxide, 409C) for 5 hours, dissolve in methanol to make exactly 50 mL. Pipet 2 mL of this solu-tion, add methanol to make exactly 25 mL, and use this solu-tion as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, ATC and ATD, of (E)-capsaicin and dihydrocapsaicin (the relative retention time to (E)-capsaicin is about 1.3) obtained with the sample solution, and the peak area, AS, of (E)-capsaicin obtained with the standard solution. Amount (mg) of total capsaicins ＝ MS × (ATC ＋ ATD)/AS × 0.032 MS: Amount (mg) of (E)-capsaicin for assay taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 281 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with phenylated silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 309C. Mobile phase: A mixture of diluted phosphoric acid (1 in 1000) and acetonitrile (3:2). Flow rate: Adjust so that the retention time of (E)-capsai-cin is about 20 minutes. System suitability— System performance: Dissolve 1 mg each of (E)-capsaicin for assay and 4-hydroxy-3-methoxybenzyl nonylic acid amide in methanol to make 50 mL. When the procedure is run with 20 mL of this solution under the above operating conditions, 4-hydroxy-3-methoxybenzyl nonylic acid amide and (E)-capsaicin are eluted in this order with the resolution between these peaks being not less than 1.5. System repeatability: When the test is repeated 6 times ‌JP XVIII Crude Drugs and Related Drugs / Carnauba Wax 1975‌‌ with 20 mL of the …
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

captopril
type: ChemicalDrugMonograph
pref label:
  en: Captopril
  ja: カプトプリル
monograph id: JP18-captopril
publisher: JP
status: Official
version: 18
molecular formula: C9H15NO3S
molecular weight: 217.29
cas number: 62571-86-2
definition:
  en: Captopril contains not less than 98.
appearance:
  en: Captopril occurs as white, crystals or crystal-line powder. It is very soluble in methanol, freely soluble in ethanol (99.5), and soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Captopril as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]25: －125 – －1349(after drying, 0.1 g, ethanol (99.5), 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Captopril according to Method 2, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So- ‌JP XVIII Official Monographs / Carbamazepine 623 lution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Captopril according to Method 1, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.20 g of Captopril in methanol to make exactly 10 mL, and use this solution as the sample solution. Separately, dissolve 15 mg of 1,1?-[3,3?-dithiobis(2-methyl-1-oxopropyl)]-L-diproline in methanol to make exactly 250 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop with a mixture of toluene and acetic acid (100) (13:7) to a distance of about 15 cm, and air-dry the plate. Place the plate in a chamber filled with iodine vapor, and allow to stand for 30 minutes: the number of the spots other than the spot cor-responding to that obtained from the standard solution and the principal spot from the sample solution is not more than two, and they are not more intense than the spot from the standard solution. 1,1?-[3,3?-Dithiobis(2-methyl-1-oxopropyl)]-L-diproline—Dissolve 0.10 g of Captopril in methanol to make exactly 20 mL, and use this solution as the sample solution. Separately, dissolve 25 mg of 1,1?-[3,3?-dithiobis(2-methyl-1-oxopropyl)]-L-diproline in methanol to make exactly 250 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of 1,1?-[3,3?-dithiobis(2-methyl-1- oxopropyl)]-L-diproline in each solution: AT is not larger than AS. Operating con…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Captopril, dissolve in 100 mL of water, add 20 mL of dilute sulfuric acid and 1 g of potassium iodide, and shake. Titrate <2.50> with 1/60 mol/L potassium iodate VS (indicator: 2 mL of starch TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 1/60 mol/L potassium iodate VS ＝ 21.73 mg of C9H15NO3S
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

carbamazepine
type: ChemicalDrugMonograph
pref label:
  en: Carbamazepine
  ja: カルバマゼピン
monograph id: JP18-carbamazepine
publisher: JP
status: Official
version: 18
molecular formula: C15H12N2O
molecular weight: 236.27
definition:
  en: Carbamazepine, when dried, contains not less than 97.
appearance:
  en: Carbamazepine occurs as a white to slightly yellow-white powder. It is odorless and tasteless at first, and leaves a slightly bitter aftertaste. It is freely soluble in chloroform, sparingly soluble in ethanol (95) and in acetone, and very slightly soluble in water and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 0.1 g of Carbamazepine add 2 mL of nitric acid, and heat on a water bath for 3 minutes: an orange-red color is produced. To 0.1 g of Carbamazepine add 2 mL of sulfuric acid, and heat on a water bath for 3 minutes: a yellow color is produced with a green fluorescence. Examine Carbamazepine under ultraviolet light: the solution shows an intense blue fluorescence. Determine the absorption spectrum of the solution obtained in the Assay as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi-ties of absorption at the same wavelengths.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Carbamazepine in 10 mL of chloroform: the solution is clear and colorless to pale yellow. Acidity—To 2.0 g of Carbamazepine add exactly 40 mL of water, stir well for 15 minutes, and filter through a glass filter (G3). To 10 mL of this filtrate add 1 drop of phenolphthalein TS and 0.50 mL of 0.01 mol/L sodium hy-droxide VS: a red color is produced. Alkalinity—To 10 mL of the filtrate obtained in (2) add 1 drop of methyl red TS and 0.50 mL of 0.01 mol/L hydrochloric acid VS: a red color is produced. Chloride <1.03>—Dissolve 0.25 g of Carbamazepine in 30 mL of acetone, add 6 mL of dilute nitric acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.20 mL of 0.01 mol/L hydrochloric acid VS add 30 mL of acetone, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.028z). Heavy metals <1.07>—Proceed with 2.0 g of Car- bamazepine according to Method 2, and perform the test. ‌624 Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 0.25 g of Carbamaze-pine in 10 mL of chloroform, and use this solution as the sample solution. Separately, dissolve 5.0 mg of iminodiben-zyl in chloroform to make exactly 100 mL, and use this solu-tion as the standard solution. Perform the test with these so-lutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solu-tion on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of toluene and methanol (19:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly potassium dichromate-sulfuric acid TS on the plate: the spots other than the principal spot obtained from the sample solution is not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44>…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Dissolve about 50 mg of Carbamazepine, previously dried and accurately weighed, in ethanol (95) to make ex-actly 250 mL. Pipet 5 mL of this solution and add ethanol (95) to make exactly 100 mL. Perform the test as directed under Ultraviolet-visible Spectrophotometry <2.24>, and de-termine the absorbance A of this solution at the wavelength of maximum absorption at about 285 nm. Amount (mg) of carbamazepine (C15H12N2O) ＝ A/490 × 50,000
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

carbidopa-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Carbidopa Hydrate
  ja: カルビドパ水和物
monograph id: JP18-carbidopa-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C10H14N2O4.H2O
molecular weight: 244.24
cas number: 38821-49-7
definition:
  en: Carbidopa Hydrate contains not less than 98.
appearance:
  en: Carbidopa Hydrate occurs as a white to yel-lowish white powder. It is sparingly soluble in methanol, slightly soluble in water, very slightly soluble in ethanol (95), and practically insoluble in diethyl ether. Melting point: about 1979C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Carbidopa Hydrate in 250 mL of a solution of hydrochloric acid in methanol (9 in 1000). Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Carbidopa RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Car-bidopa Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Carbidopa RS: both spectra exhibit similar intensi-ties of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －21.0 – －23.59(1 g, alumi- num (III) chloride TS, 100 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Carbidopa Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 50 mg of Carbidopa Hydrate in 70 mL of the mobile phase, by warming and using ultrasonication, if necessary. After cooling, add the mobile phase to make 100 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area from both so-lutions by the automatic integration method: the total area of the peaks other than carbidopa obtained from the sample solution is not larger than the peak area of carbidopa from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 3 times as long as the retention time of carbidopa. System suitability— System performance, and system repeatability: Proceed as directed in the system suitability in the Assay. Test for required detectability: To exactly 2 mL of the standard solution add the mobile phase to make exactly 20 mL. Confirm that the peak area of carbidopa obtained with 20 mL of this solution is equivalent to 7 to 13z of that with 20 mL of the standard solution. Loss on drying <2.41> 6.9 – 7.9z (1 g, in vacuum not exceeding 0.67 kPa, 1009C, 6 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 50 mg each of Carbidopa Hydrate and Carbidopa RS (separately determine the loss on drying <2.41> under the same conditions as Carbidopa Hy-drate), and dissolve each in 70 mL of the mobile phase, by warming and using ultrasonication if necessary. After cool-ing, add the mobile phase to make exactly 100 mL, and use these solutions as the sample solution and the standard solu-tion, respectively. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine the peak areas, AT and AS, of carbidopa in each solution. Amount (mg) of carbidopa hydrate (C10H14N2O4.H2O) ＝ MS × AT/AS × 1.080 MS: Amount (mg) of Carbidopa RS taken, calculated on the dried basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column 4 mm in inside diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (7 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: To 950 mL of 0.05 mol/L sodium dihydro-gen phosphate TS add 50 mL of ethanol (95), and adjust the pH to 2.7 with phosphoric acid. ‌626 Flow rate: Adjust so that the retention time of carbidopa is about 6 minutes. System suitability— ‌System performance: Dissolve 50 mg each of Carbidopa Hydrate and methyldopa in 100 mL of the mobile phase. When the procedure is run with 20 mL of this solution under the above operating conditions, methyldopa and carbidopa are eluted in this order with the resolution between these peaks being not less than 0.9. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of carbidopa is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

carbon-dioxide
type: ChemicalDrugMonograph
pref label:
  en: Carbon Dioxide
  ja: 二酸化炭素
monograph id: JP18-carbon-dioxide
publisher: JP
status: Official
version: 18
molecular formula: CO2
molecular weight: 44.01
cas number: 124-38-9
definition:
  en: Carbon Dioxide contains not less than 99.
appearance:
  en: Carbon Dioxide is a colorless gas at room tem-perature and under atmospheric pressure. It is odorless. A 1 mL volume of Carbon Dioxide dissolves in 1 mL of water, and the solution is slightly acid. 1000 mL of Carbon Dioxide at 09C and under a pressure of 101.3 kPa weighs 1.978 g.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Pass 100 mL of Carbon Dioxide through a carbon dioxide measuring detector tube: the detec-tor tube is changed to a stipulated color tone by each detec-tor tube, provided that the detector tube with a upper limit of measurement of not less than 10z is used. (2) Pass Carbon Dioxide into calcium hydroxide TS: a white precipitate is produced. Collect the precipitate, and add acetic acid (31): it dissolves with effervescence.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—Place 50 mL of freshly boiled and cooled water in a Nessler tube, and pass 1000 mL of Carbon Dioxide into it for 15 minutes through an introducing tube about 1 mm in diameter extending to 2 mm from the bottom of the Nessler tube, then add 0.10 mL of methyl orange TS: the solution is not more colored than the following control solution. Control solution: To 50 mL of freshly boiled and cooled water in a Nessler tube add 0.10 mL of methyl orange TS and 1.0 mL of 0.01 mol/L hydrochloric acid VS. Hydrogen phosphide, hydrogen sulfide or reducing ＝ MS × QT/QS × V/4 5 9 4 organic substances—Place 25 mL of silver nitrate-ammonia TS and 3 mL of ammonia TS in each of two Nessler tubes MS: Amount of L-carbocisteine for assay taken Internal standard solution—A solution of nicotinic acid (9 in 10,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave- A and B, and designate the solution in each tube as solution A and solution B, respectively. Pass 1000 mL of Carbon Di-oxide into solution A in the same manner as directed in (1): the turbidity and color of this solution are the same as that of solution B. ‌628 Carbon monoxide—Pass a specified amount of Car-bon Dioxide through a carbon monoxide measuring detector tube: the concentration of carbon monoxide is less than 15 ppm, provided that the passing amount (mL) of Carbon Dioxide is stipulated according to each detector tube.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Place 125 mL of a solution of potassium hydroxide (1 in 2) in a gas pipet of suitable capacity. Measure exactly about 100 mL of Carbon Dioxide in a 100-mL gas buret filled with water. Force the entire volume of gas into the gas pipet, and shake for 5 minutes. Draw some of the unab-sorbed gas into the gas buret, measure the volume, force the residual back upon the surface of the liquid in the gas pipet, and repeat this procedure until a constant volume of the residual reading is obtained. Determine the volume V (mL) of the residual gas. Calculate the volume of the sample and V on the basis of the gas volume at 209C and at 101.3 kPa. Volume (mL) of carbon dioxide (CO2) ＝ volume (mL) of the sample － V (mL)
storage conditions:
  en: Containers—Cylinders. Storage—Not exceeding 409C.

carboplatin
type: ChemicalDrugMonograph
pref label:
  en: Carboplatin
  ja: カルボプラチン
monograph id: JP18-carboplatin
publisher: JP
status: Official
version: 18
molecular formula: C6H12N2O4Pt
molecular weight: 371.25
cas number: 41575-94-4
definition:
  en: Carboplatin contains not less than 98.
appearance:
  en: Carboplatin occurs as white, crystals or crys-talline powder. It is sparingly soluble in water, and very slightly soluble in ethanol (99.5). Melting point: about 2009C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2 mL of a solution of Carboplatin (1 in 100) add 2 to 3 drops of diluted tin (II) chloride TS (1 in 15), and allow to stand for 30 minutes: a yellowish brown precipitate is formed. (2) Determine the infrared absorption spectrum of Carboplatin as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Carboplatin RS: both spectra exhibit similar intensi-ties of absorption at the same wave numbers. pH <2.54> Dissolve 0.10 g of Carboplatin in 10 mL of water: the pH of this solution is 5.0 to 7.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) 1,1-Cyclobutanedicarboxylic acid—Weigh ac-curately about 40 mg of Carboplatin, dissolve in the mobile phase to make exactly 20 mL, and use this solution as the sample solution. Separately, weigh accurately about 25 mg of 1,1-cyclobutanedicarboxylic acid, and dissolve in the mobile phase to make exactly 100 mL. Pipet 4 mL of this solution, add the mobile phase to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 25 mL each of the sample solution and standard are eluded in this order with the resolution between these peaks being not less than 3. System repeatability: When the test is repeated 6 times with 25 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of 1,1-cyclobutanedicarboxylic acid is not more than 2.0z. (2) Related substances—Dissolve 25 mg of Carboplatin in 25 mL of water, and use this solution as the sample solu-tion. Perform the test with 10 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method. Calculate the amount of the peaks by the area percentage method: the amount of the peak, having the relative retention time of about 0.8 to car-boplatin, is not more than 0.25z, the amount of the peak other than carboplatin and the peak mentioned above is not more than 0.1z, and the total amount of the peaks other than carboplatin is not more than 0.5z. Operating conditions— Detector, column, column temperature, mobile phases A and B, and flow rate: Proceed as directed in the operating conditions in the Assay. Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. ‌JP XVIII Official Monographs / Carboplatin Injection 629 Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) Time after injection of sample (min) Mobile phase A (volz) Mobil…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 25 mg each of Carboplatin and Carboplatin RS (separately determine the loss on drying <2.41> under the same conditions as Carboplatin), dissolve separately in water to make exactly 25 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of carboplatin in each solution. Amount (mg) of carboplatin (C6H12N2O4Pt) ＝ MS × AT/AS MS: Amount (mg) of Carboplatin RS taken, calculated on the dried basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 220 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with phenylhexylsilanized silica gel for liquid chromatography (5 mm in particle diame-ter). Column temperature: A constant temperature of about 279C. Mobile phase A: Dissolve 8.5 g of tetrabutylammonium hydrogensulfate in 80 mL of water, add 3.4 mL of phos-phoric acid, and adjust to pH 7.5 with a solution of sodium hydroxide (43 in 100). To 20 mL of this solution add water to make 1000 mL. Mobile phase B: Dissolve 8.5 g of tetrabutylammonium hydrogensulfate in 80 mL of water, add 3.4 mL of phos-phoric acid, and adjust to pH 7.5 with a solution of sodium hydroxide (43 in 100). To 20 mL of this solution add water to make 800 mL, and add 200 mL of acetonitrile. Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. 0 – 15 100 0 15 – 35 100 → 0 0 → 100 Flow rate: 0.5 mL per minute. System suitability— System performance: To 9 mL of the standard solution add 1 mL of diluted hydrogen peroxide TS (1 in 60), and allow to stand at room temperature for not less than 1 hour. When the procedure is run with 10 mL of this solution under the above operating conditions, the resolution …
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

carboxymethylcellulose
type: ChemicalDrugMonograph
pref label:
  en: Carboxymethylcellulose
  ja: カルメロース
monograph id: JP18-carboxymethylcellulose
publisher: JP
status: Official
version: 18
cas number: 9000-11-7
appearance:
  en: Carmellose occurs as a white powder. It is practically insoluble in ethanol (95). It swells with water to form suspension. It becomes viscid in sodium hydroxide TS. It is hygroscopic.◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of Carmellose as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. (2) The pH <2.54> of a suspension, obtained by shaking 1 g of Carmellose with 100 mL of water, is between 3.5 and 5.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride—Shake well 0.8 g of Carmellose with 50 mL of water, add 10 mL of sodium hydroxide TS to dis- JP XVIII Official Monographs / Carmellose Calcium 631 ‌solve, and add water to make 100 mL. Heat 20 mL of this solution with 10 mL of dilute nitric acid in a water bath until a flocculent precipitate is produced, cool, centrifuge, and take out the supernatant liquid. Wash the precipitate with three 10-mL portions of water by centrifuge each time, com-bine the supernatant liquid and the washings, and add water to make 100 mL. Take 25 mL of this solution in a Nessler tube, add 6 mL of dilute nitric acid and water to make 50 mL, and use this solution as the test solution. Separately, to 0.40 mL of 0.01 mol/L hydrochloric acid VS add 6 mL of dilute nitric acid and water to make 50 mL, and use this solu-tion as the control solution. To the test solution and the con-trol solution add 1 mL each of silver nitrate TS, ◆mix,◆ and allow to stand protected from light for 5 minutes. Compare the opalescence developed in both solutions ◆against a black background by viewing downward or transversely◆. The opalescence in the test solution is not more intense than that in the control solution (not more than 0.36z). Sulfate—Shake well 0.40 g of Carmellose with 25 mL of water, add 5 mL of sodium hydroxide TS to dissolve, and add 20 mL of water. Heat this solution with 2.5 mL of hydrochloric acid in a water bath until a flocculent precipi-tate is produced, cool, centrifuge, and take out the superna-tant liquid. Wash the precipitate with three 10-mL portions of water by centrifuge each time, combine the supernatant liquid and the washings, and add water to make 100 mL. Filter this solution, discard the first 5 mL of the filtrate, take 25 mL of the subsequent filtrate in a Nessler tube, add 1 mL of dilute hydrochloric acid and water to make 50 mL, and use this solution as the test solution. Separately, to 1.5 mL of 0.005 mol/L sulfuric acid VS add 1 mL of dilute hydro-chloric acid and…

carmofur
type: ChemicalDrugMonograph
pref label:
  en: Carmofur
  ja: カルモフール
monograph id: JP18-carmofur
publisher: JP
status: Official
version: 18
molecular formula: C11H16FN3O3
molecular weight: 257.26
definition:
  en: Carmofur, when dried, contains not less than 98.
appearance:
  en: Carmofur occurs as a white crystalline pow-der. It is very soluble in N,N-dimethylformamide, freely solu-ble in acetic acid (100), soluble in diethyl ether, sparingly soluble in methanol and in ethanol (99.5), and practically in-soluble in water. Melting point: about 1119C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Proceed with 5 mg of Carmofur as di-rected under Oxygen Flask Combustion Method <1.06>, using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as the absorbing liquid, and prepare the test solution: the test solution responds to Qualitative Tests <1.09> (2) for fluoride. Determine the absorption spectrum of a solution of Carmofur in a mixture of methanol and phosphoric acid-acetic acid-boric acid buffer solution (pH 2.0) (9:1) (1 in 100,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Car-mofur, previously dried, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Carmofur according to Method 2, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 10 ppm). (2) Related substances—Dissolve 0.20 g of Carmofur in 10 mL of a mixture of methanol and acetic acid (100) (99:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of methanol and acetic acid (100) (99:1) to make exactly 500 mL, and use this solu-tion as the standard solution. Perform the test with these so-lutions as directed under Thin-layer Chromatography <2.03>. Spot 15 mL each of the sample solution and standard solu-tion on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of toluene and acetone (5:3) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot from the sample solution are not more intense than the spot from the standard solution. After exposure of the plate to bromine vapor for 30 second, spray evenly a solution of fluorescein in ethanol (95) (1 in 2500): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, in vacu-um, 509C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Carmofur, previ-ously dried, dissolve in 20 mL of N,N-dimethylformamide, and titrate <2.50> with 0.1 mol/L tetramethylammonium hy-droxide-methanol VS until the color of the solution changes from yellow through blue-green to blue (indicator: 3 drops of thymol blue-dimethylformamide TS). Each mL of 0.1 mol/L tetramethylammonium hydroxide-methanol VS ＝ 25.73 mg of C11H16FN3O3
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

carteolol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Carteolol Hydrochloride
  ja: カルテオロール塩酸塩
monograph id: JP18-carteolol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C16H24N2O3.HCl
molecular weight: 328.83
cas number: 51781-21-6
appearance:
  en: Carteolol Hydrochloride occurs as white, crys tals or crystalline powder. It is soluble in water, sparingly soluble in methanol, very slightly soluble in ethanol (95) and in acetic acid (100), and practically insoluble in diethyl ether. The pH of a solution of 1.0 g of Carteolol Hydrochloride in 100 mL of water is between 5.0 and 6.0. The solution of Carteolol Hydrochloride (1 in 20) shows no optical rotation. Melting point: about 2779C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.1 g of Carteolol Hydrochlo-ride in 5 mL of water, and add 5 drops of Reinecke salt TS: a light red precipitate is formed. Determine the absorption spectrum of a solution of Carteolol Hydrochloride (1 in 100,000) as directed under Ul-traviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Car-teolol Hydrochloride as directed in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Carteolol Hydrochloride (1 in 50) re-sponds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Carteolol Hydrochloride in 30 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g of Car- teolol Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Carteolol Hydrochloride according to Method 3, and per-form the test (not more than 2 ppm). Related substances—Dissolve 0.20 g of Carteolol Hy-drochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 2 mL of the sample solution, and add methanol to make exactly 100 mL. Pipet 1 mL of this solution, add methanol to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chloroform, methanol and ammonia solution (28) (50:20:1) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Carteolol Hydro-chloride, previously dried, add 30 mL of acetic acid (100), dissolve by heating on a water bath, and cool. After adding 70 mL of acetic anhydride, titrate <2.50> with 0.1 mol/L per-chloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 32.88 mg of C16H24N2O3.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

carvedilol
type: ChemicalDrugMonograph
pref label:
  en: Carvedilol
  ja: カルベジロール
monograph id: JP18-carvedilol
publisher: JP
status: Official
version: 18
molecular formula: C24H26N2O4
molecular weight: 406.47
definition:
  en: Carvedilol, when dried, contains not less than 99.
appearance:
  en: Carvedilol occurs as white to pale yellow-white, crystals or crystalline powder. It is freely soluble in acetic acid (100), sparingly soluble in methanol, slightly soluble in ethanol (99.5), and practically insoluble in water. A solution of Carvedilol in methanol (1 in 100) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Carvedilol in methanol (1 in 200,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Car-vedilol as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Wrap 2.0 g of Car-vedilol with a filter paper for quantitative analysis, then proceed according to Method 4, and perform the test. Pre-pare the control solution as follows: Put a filter paper for quantitative analysis in a crucible, add 10 mL of a solution of magnesium nitrate hexahydrate in ethanol (95) (1 in 10), then proceed as directed for the test solution, and add 2.0 mL of Standard Lead Solution and water to make 50 mL (not more than 10 ppm). (2) Related substances—Dissolve 65 mg of Carvedilol in 100 mL of the mobile phase. To 1 mL of this solution add the mobile phase to make 10 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method: the area of the peak other than carvedilol obtained from the sample solution is not larger than 3/20 times the peak area of carvedilol from the stand-ard solution, and the total area of the peaks other than car-vedilol from the sample solution is not larger than 1/2 times the peak area of carvedilol from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 240 nm). ‌638 Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 559C. Mobile phase: Dissolve 2.72 g of potassium dihydrogen phosphate in 900 mL of water, adjust to pH 2.0 with phos-phoric acid, and add water to make 1000 mL. To 650 mL of this solution add 350 mL of acetonitrile. Flow rate: Adjust so that the retention time of carvedilol is about 4 minutes. Time span of measurem…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Carvedilol, previ-ously dried, dissolve in 60 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform the blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 40.65 mg of C24H26N2O4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cefaclor
type: ChemicalDrugMonograph
pref label:
  en: Cefaclor
  ja: セファクロル
monograph id: JP18-cefaclor
publisher: JP
status: Official
version: 18
molecular formula: C15H14ClN3O4S
molecular weight: 367.81
cas number: 53994-73-3
definition:
  en: Cefaclor contains not less than 950 mg (potency) and not more than 1020 mg (potency) per mg, calcu-lated on the anhydrous basis.
appearance:
  en: Cefaclor occurs as a white to yellow-white crystalline powder. It is slightly soluble in water and in methanol, and practi-cally insoluble in N,N-dimethylformamide and in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefaclor (1 in 50,000) as directed under Ultravio-let-visible Spectrophotometry <2.24>, and compare the spec-trum with the Reference Spectrum: both spectra exhibit simi-lar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cefaclor as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolve 40 mg of Cefaclor in 0.5 mL of heavy water for nuclear magnetic resonance spectroscopy and 1 drop of deuterated hydrochloric acid for nuclear magnetic resonance spectroscopy, and determine the 1H spectrum of this solution as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using sodium 3-trimethylsilylpropanesulfonate for nuclear magnetic resonance spectroscopy as an internal ref-erence compound: it exhibits an AB type quartet signal A at around d 3.7 ppm, and a singlet signal or a sharp multiplet signal B at around d 7.6 ppm. The ratio of the integrated in-tensity of each signal, A:B, is about 2:5. Perform the test with Cefaclor as directed under Flame Coloration Test <1.04> (2): a green color appears. D Optical rotation <2.49> [a]20: ＋105 – ＋1209(0.1 g calcu-lated on the anhydrous basis, water, 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Cefaclor according to Method 2, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution by suspend- ing 1.0 g of Cefaclor in 10 mL of N,N-dimethylformamide, and perform the test (not more than 2 ppm). Related substances—Dissolve 50 mg of Cefaclor in 10 mL of sodium dihydrogen phosphate TS (pH 2.5), and use this solution as the sample solution. Pipet 1 mL of the sam-ple solution, add sodium dihydrogen phosphate TS (pH 2.5) to make exactly 100 mL, and use this solution as the stand-ard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the area of the peaks other than cefaclor obtained from the sample solution are not larger than 1/2 times the peak area of cefaclor from the standard solution, and the total area of the peaks other than cefaclor from the sample solution is not larger than 2 times of the peak area of cefaclor from the standard solution. If necessary, proceed with 20 mL of sodium dihydrogen phosphate TS (pH 2.5) in the same manner as above to compensate the base line. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 220 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase A: Dissolve 7.8 g of sodium dihydrogen phosphate dihydrate in 1000 mL of water, and adjust the pH to 4.0 with phosphoric acid. Mobile phase B: To 550 mL of the mobile phase A add 450 mL of acetonitrile for liquid chromatography. Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as direc…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefaclor and Cefaclor RS, equivalent to about 50 mg (potency), and dis-solve each in 0.1 mol/L phosphate buffer solution (pH 4.5) to make exactly 50 mL. Pipet 10 mL each of these solutions, add exactly 10 mL of the internal standard solution, add 0.1 JP XVIII Official Monographs / Cefaclor Capsules 641 ‌mol/L phosphate buffer solution (pH 4.5) to make 50 mL, and use these solutions as the sample solution and the stand-ard solution, respectively. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and calculate the ratios, QT and QS, of the peak area of cefaclor to that of the internal standard. Amount [mg (potency)] of cefaclor (C15H14ClN3O4S) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Cefaclor RS taken Internal standard solution—A solution of 4-aminoacetophe-none in 0.1 mol/L phosphate buffer solution (pH 4.5) (1 in 700). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 6.8 g of potassium dihydrogen phosphate in 1000 mL of water, and adjust the pH to 3.4 with diluted phosphoric acid (3 in 500). To 940 mL of this solution add 60 mL of acetonitrile. Flow rate: Adjust so that the retention time of cefaclor is about 7 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, cefaclor and the internal standard are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cefadroxil
type: ChemicalDrugMonograph
pref label:
  en: Cefadroxil
  ja: セファドロキシル
monograph id: JP18-cefadroxil
publisher: JP
status: Official
version: 18
molecular formula: C16H17N3O5S
molecular weight: 363.39
cas number: 50370-12-2
definition:
  en: Cefadroxil contains not less than 950 mg (potency) and not more than 1020 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefadroxil occurs as a white to light yellow-white powder. It is sparingly soluble in water, slightly soluble in metha-nol, and very slightly soluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefadroxil (1 in 50,000) as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefadroxil RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cefadroxil as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cefadroxil RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefadroxil in a mixture of heavy water for nuclear magnetic resonance spectroscopy and deuterated hydrochloric acid (3:1) (1 in 10), using sodium 3-(trimethylsilyl)propionate-d4 for nuclear magnetic resonance spectroscopy as an internal reference compound, as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>: it exhibits a singlet signal A at around d 2.1 ppm, a doublet signal B at around d 7.0 ppm, and a doublet signal C at around d 7.5 ppm. The ratio of integrated intensity of each signal, A:B:C, is about 3:2:2. D Optical rotation <2.49> [a]25: ＋164 – ＋1829(0.6 g calcu-lated on the anhydrous basis, water, 100 mL, 100 mm). pH <2.54> Dissolve 1.0 g of Cefadroxil in 200 mL of water: pH of the solution is between 4.0 and 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of ‌646 Cefadroxil according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 0.1 g of Cefadroxil in 4 mL of a mixture of ethanol (99.5), water and diluted hydro-chloric acid (1 in 5) (75:22:3), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of ethanol (99.5), water and diluted hydrochloric acid (1 in 5) (75:22:3) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 2 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatogra-phy. Develop with a mixture of ethyl acetate, water, ethanol (99.5) and formic acid (14:5:5:1) to a distance of about 12 cm, and air-dry the plate. Spray evenly ninhydrin-citric acid-acetic acid TS on the plate, and heat the plate at 1009C for 10 minutes: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Water <2.48> Not less than 4.2z and not more than 6.0z (0.5 g, volumetric titration, direct titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefadroxil and Cefadroxil RS, equivalent to about 50 mg (potency), dissolve each in water to make exactly 500 mL, and use these solu-tions as the sample solution and the standard solution, re-spectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of cefadroxil in each solution. Amount [ mg (potency)] of cefadroxil (C16H17N3O5S) ＝ MS × AT/AS × 1000 MS: amount [mg (potency)] of Cefadroxil RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 262 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of a solution of potassium dihy-drogenphosphate (17 in 12,500) and methanol (17:3). Flow rate: Adjust so that the retention time of cefadroxil is about 5 minutes. System suitability— System performance: Dissolve about 5 mg (potency) of Cefadroxil and about 10 mg (potency) of propylene glycol cefatrizine in 50 mL of water. When the procedure is run with 10 mL of this solution under the above operating condi-tions, cefadroxil and cefatrizine are eluted in this order with the resolution between these peaks being not less than 4. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak areas of cefadroxil is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cefalexin
type: ChemicalDrugMonograph
pref label:
  en: Cefalexin
  ja: セファレキシン
monograph id: JP18-cefalexin
publisher: JP
status: Official
version: 18
molecular formula: C16H17N3O4S
molecular weight: 347.39
cas number: 15686-71-2
definition:
  en: Cefalexin contains not less than 950 mg (potency) and not more than 1030 mg (potency) per mg, calcu-lated on the anhydrous basis.
appearance:
  en: Cefalexin occurs as a white to light yellow-white, crystals or crystalline powder. It is sparingly soluble in water, slightly soluble in metha-nol, and practically insoluble in ethanol (95) and in N,N-dimethylformamide. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefalexin (3 in 100,000) as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cefalexin as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefalexin in heavy water for nuclear magnetic resonance spectroscopy (1 in 200) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using sodium 3-trimethylsilylpropane-sulfonate for nuclear magnetic resonance spectroscopy as an internal reference compound: it exhibits a singlet signal A at around d 1.8 ppm, and a singlet or a sharp multiplet signal B at around d 7.5 ppm. The ratio of integrated intensity of these signals, A:B, is about 3:5. D Optical rotation <2.49> [a]20: ＋144 – ＋1589(0.125 g calcu-lated on the anhydrous basis, water, 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cefalexin according to Method 4, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Cefalexin by suspending in 10 mL of N,N-dimethylfor-mamide, and perform the test (not more than 2 ppm). Related substances—Dissolve about 25 mg of Cefalexin in a solution of potassium dihydrogenphosphate (9 in 500) to make 5 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a solution of potassium dihydrogenphosphate (9 in 500) to make ex-actly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solu-tion and standard solution as directed under Liquid Chroma-tography <2.01> according to the following conditions, and determine the areas of each peak by the automatic integra-tion method. If necessary, correct the change of the base-line due to the potassium dihydrogenphosphate solution by proceeding in the same manner with 20 mL of a solution of potassium dihydrogenphosphate (9 in 500): each peak area other than cefalexin from the sample solution is not larger equivalent to 1.8 to 2.2z of that with 20 mL of the standard solution. System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of cefalexin are not less than 150,000 and between 0.8 and 1.3, respectively. System repeatability: When the test is repeated 3 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the reten-tion time and the peak areas of cefalexin are not more than 2.0z, respectively. Water <2.48> Not more than 8.0z (0.2 g, volumetric titra-tion, back titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefalexin and Cefalexin RS, equivalent to about 25 mg (potency), dissolve each in 0.1 mol/L phosphate buffer solution (pH 4.5) to make exactly 25 mL. Pipet 10 mL of these solutions, add exactly 5 mL of the internal standard solution, then add 0.1 mol/L phosphate buffer solution (pH 4.5) to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample so-lution and standard solution as directed under Liquid Chro-matography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of cefalexin to that of the internal standard. than the peak area of cefalexin from the standard solution, and the total area of the peaks other than cefalexin from the sample solution which are larger than 1/50 times the peak Amount [ mg (potency)] of cefalexin (C ＝ MS × QT/QS × 1000 16H17N3O4S) area of cefalexin from the standard solution is not larger than 5 times of the peak area of cefalexin from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase A: Dissolve 1.0 g of sodium 1-pentanesul-fonate in 1000 mL of water, add 15 mL of triethylamine, and adjust to pH 2.5 with phosphoric acid. Mobile phase B: Dissolve 1.0 g of sodium 1-pentanesul-fonate in 300 mL of water, add 15 mL of triethylamine, and adjust to pH 2.5 with phosphoric acid. To this solution add 350 mL of acetonitrile and 350 mL of methanol. Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. MS: amount [mg (potency)] of Cefalexin RS taken Internal standard solution—A solution of m-hydroxy-acetophenone in 0.1 mol/L phosp…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cefatrizine-propylene-glycolate
type: ChemicalDrugMonograph
pref label:
  en: Cefatrizine Propylene Glycolate
  ja: セファトリジンプロピレングリコール
monograph id: JP18-cefatrizine-propylene-glycolate
publisher: JP
status: Official
version: 18
molecular formula: C18H18N6O5S2.C3H8O2
molecular weight: 538.6
definition:
  en: Cefatrizine Propylene Glycolate contains not less than 816 mg (potency) and not more than 876 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefatrizine Propylene Glycolate occurs as a white to yellowish white powder. It is sparingly soluble in water, and practically insoluble in methanol and in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefatrizine Propylene Glycolate (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefatrizine Propylene Glyco-late RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cefatrizine Propylene Glycolate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum or the spectrum of Cefatrizine Propylene Glycolate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefatri-zine Propylene Glycolate in a mixture of heavy water for nuclear magnetic resonance spectroscopy and deuterated hy-drochloric acid for nuclear magnetic resonance spectroscopy (3:1) (1 in 10), using sodium 3-(trimethylsilyl)propionate-d4 for nuclear magnetic resonance spectroscopy as an internal reference compound, as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>: it exhibits a doublet signal A at around d 1.2 ppm, a doublet signal B at around d 7.0 ppm, a doublet signal C at around d 7.5 ppm and a singlet signal D at around d 8.3 ppm. The ratio of integrated inten-sity of these signals, A:B:C:D, is about 3:2:2:1. D Optical rotation <2.49> [a]20: ＋52 – ＋589(2.5 g calculated on the anhydrous bases, 1 mol/L hydrochloric acid TS, 50 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Cefatrizine Propylene Glycolate according to Method 2, and ‌JP XVIII Official Monographs / Cefatrizine Propylene Glycolate for Syrup 655 perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Cefatrizine Propylene Glycolate according to Method 3, and perform the test (not more than 2 ppm). Use a solution of magnesium nitrate hexahydrate in ethanol (1 in 25). Related substances—Dissolve 25 mg of Cefatrizine Propylene Glycolate in 5 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop with a mixture of 1-butanol, water and acetic acid (100) (3:1:1) to a distance of about 12 cm, and air-dry the plate. Spray evenly ninhydrin-citric acid-acetic acid TS on the plate, and heat the plate at 1009C for 10 minutes: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the stand-ard solution. Water <2.48> Not more than 2.0z (0.5 g, volumetric titra-tion, direct titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefatrizine Propy-lene Glycolate and Cefatrizine Propylene Glycolate RS, equivalent to about 0.1 g (potency), dissolve each in water to make exactly 500 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of cefatrizine in each solution. Cefatrizine Propylene Glycolate for Syrup
type: PharmacopoeiaMonograph

cefcapene-pivoxil-hydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Cefcapene Pivoxil Hydrochloride Hydrate
  ja: セフカペン ピボキシル塩酸塩水和物
monograph id: JP18-cefcapene-pivoxil-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C23H29N5O8S2.HCl.H2O
molecular weight: 622.11
definition:
  en: Cefcapene Pivoxil Hydrochloride Hydrate contains not less than 722 mg (potency) and not more than 764 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefcapene Pivoxil Hydrochloride Hydrate oc-curs as a white to pale yellow-white, crystalline powder or mass. It has slightly a characteristic odor. It is freely soluble in N,N-dimethylformamide and in methanol, soluble in ethanol (99.5), slightly soluble in water, and practically insoluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefcapene Pivoxil Hydrochloride Hydrate in methanol (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cef-capene Pivoxil Hydrochloride RS prepared in the same man-ner as the sample solution: both spectra exhibit similar inten-sities of absorption at the same wavelengths. Determine the infrared absorption spectra of Cefca- JP XVIII Official Monographs / Cefcapene Pivoxil Hydrochloride Hydrate 661 pene Pivoxil Hydrochloride Hydrate and Cefcapene Pivoxil Hydrochloride RS as directed in the paste method under In-frared Spectrophotometry <2.25>, and compare these spec-tra: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefca-pene Pivoxil Hydrochloride Hydrate in deuterated methanol for nuclear magnetic resonance spectroscopy (1 in 50) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using tetramethylsilane for nuclear magnetic reso- nance spectroscopy as an internal reference compound: it exhibits a triplet signal A at around d 6.3 ppm, and a single signal B at around d 6.7 ppm, and the ratio of integrated intensity of each signal, A:B, is about 1:1. Dissolve 10 mg of Cefcapene Pivoxil Hydrochloride Hydrate in 2 mL of a mixture of water and methanol (1:1), and add 1 drop of silver nitrate TS: a white precipitate is formed. D Optical rotation <2.49> [a]20: ＋51 – ＋549(0.1 g calculated on the anhydrous basis, methanol, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cefcapene Pivoxil Hydrochloride Hydrate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substance I—Dissolve an amount of Cefca-pene Pivoxil Hydrochloride Hydrate, equivalent to about 10 mg (potency), in 2 mL of methanol, add a mixture of water and methanol (1:1) to make 50 mL, and use this solution as the sample solution. Perform the test with 30 mL of the sam-ple solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method. If nec-essary, compensate the base-line by performing in the same manner as the test with 30 mL of a mixture of water and methanol (1:1). Measure the amount of the peak other than cefcapene pivoxil by the area percentage method: the amounts of the peaks, having the relative retention times of about 1.5 and about 1.7 to cefcapene pivoxil, are not more than 0.2z, respectively. The amount of the peaks other than the peaks mentioned above is not more than 0.1z, and the total of them is not more than 1.5z. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 265 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 209C. Mobile phase A: Dissolve 5.99 g of potassium dihydrogen phosphate in water to make 1100 mL. To this solution add a solution prepared by dissolving 1.89 g of tetra-n-pentylam-monium bromide in methanol to make 1000 mL. Mobile phase B: A mixture of methanol and water (22:3). Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) 0 – 20 20 – 40 98 → 5…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefcapene Pivoxil Hydrochloride Hydrate and Cefcapene Pivoxil Hydrochlo-ride RS, equivalent to about 20 mg (potency), and dissolve each in a mixture of water and methanol (1:1) to make exactly 50 mL. Pipet 10 mL each of these solutions, add exactly 10 mL of the internal standard solution and the mixture of water and methanol (1:1) to them to make 50 mL, and use these solutions as the sample solution and the stand-ard solution, respectively. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and calculate the ratios, QT and QS, of the peak area of cefcapene pivoxil to that of the internal standard. Cefcapene Pivoxil Hydrochloride Fine Granules
type: PharmacopoeiaMonograph

cefdinir
type: ChemicalDrugMonograph
pref label:
  en: Cefdinir
  ja: セフジニル
monograph id: JP18-cefdinir
publisher: JP
status: Official
version: 18
molecular formula: C14H13N5O5S2
molecular weight: 395.41
cas number: 91832-40-5
definition:
  en: Cefdinir contains not less than 930 mg (potency) and not more than 1020 mg (potency) per mg.
appearance:
  en: Cefdinir occurs as a white to light yellow crys-talline powder. It is practically insoluble in water, in ethanol (95) and in diethyl ether. It dissolves in 0.1 mol/L phosphate buffer solution (pH 7.0).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectra of so-lutions of Cefdinir and Cefdinir RS in 0.1 mol/L phosphate buffer solution (pH 7.0) (1 in 100,000) as directed under Ul-traviolet-visible Spectrophotometry <2.24>, and compare these spectra: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectra of Cef-dinir and Cefdinir RS as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare these spec-tra: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefdinir in a mixture of deuterated dimethyl sulfoxide for nuclear magnetic resonance spectroscopy and heavy water for nuclear magnetic resonance spectroscopy (4:1) (1 in 10), using tetramethylsilane for nuclear magnetic resonance spec-troscopy as an internal reference compound, as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>: it exhibits multiplet signals, A at around d 5.0 – 6.1 ppm and B at around d 6.4 – 7.5 ppm. The ratio of integrated intensity of each signal, A:B is about 2:1. D Optical rotation <2.49> [a]20: －58 – －669 (0.25 g, 0.1 mol/L phosphate buffer solution (pH 7.0), 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cefdinir according to Method 2, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 10 ppm). (2) Related substances—Dissolve about 0.1 g of Cefdinir in 10 mL of 0.1 mol/L phosphate buffer solution (pH 7.0). To 3 mL of this solution add tetramethylammonium hydrox-ide TS (pH 5.5) to make 20 mL, and use this solution as the sample solution. Perform the test with 10 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area by the automatic integration method, and calculate the amounts of their peaks by the area percentage method: the amount of the peaks, having the relative retention time of about 0.7, about 1.2 and about 1.5 to cefdinir, are not more than 0.7z, not more than 0.3z and not more than 0.8z, respectively, the total amount of the peaks, having the rela-tive retention time of about 0.85, about 0.93, about 1.11 and about 1.14, is not more than 0.4z, and the amount of the peak other than cefdinir and the peaks mentioned above is not more than 0.2z. And the total amount of the peaks other than cefdinir is not more than 3.0z. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase A: To 1000 mL of tetramethylammonium hydroxide TS (pH 5.5) add 0.4 mL of 0.1 mol/L disodium dihydrogen ethylenediamine tetraacetate TS. ‌JP XVIII Official Monographs / Cefdinir Capsules 665 Mobile phase B: To 500 mL of tetramethylammonium hy-droxide TS (pH 5.5) add 300 mL of acetonitrile for liquid chromatography and 200 mL of methanol, and add 0.4 mL of 0.1 mol/L disodium dihydrogen ethylenediamine tetraace-tate TS. Flowing of mob…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefdinir and Cef-dinir RS equivalent to about 20 mg (potency), dissolve each in 0.1 mol/L phosphate buffer solution (pH 7.0) to make ex-actly 100 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly 5 mL of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of cefdinir in each solution. Amount [ mg (potency)] of cefdinir (C14H13N5O5S2) ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Cefdinir RS taken this solution add 60 mL of acetonitrile for liquid chromatog-raphy and 40 mL of methanol. Flow rate: Adjust so that the retention time of cefdinir is about 8 minutes. System suitability— System performance: Dissolve 2 mg of Cefdinir RS and 5 mg of cefdinir lactam ring-cleavage lactones in 10 mL of 0.1 mol/L phosphate buffer solution, pH 7.0. When the proce-dure is run with 5 mL of this solution under the above operat-ing conditions, peak 1 and peak 2 of cefdinir lactam ring-cleavage lactones separated into 4 peaks, cefdinir, peak 3 and peak 4 of remaining cefdinir lactam ring-cleavage lactones are eluted in this order. The resolution between the peak 2 of cefdinir lactam ring-cleavage lactone and that of cefdinir is not less than 1.2. The number of theoretical plates and the symmetry factor of the peak of cefdinir are not less than 2000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 5 mL of the standard solution under the above operating conditions, the relative standard deviation of the peak areas of cefdinir is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cefditoren-pivoxil
type: ChemicalDrugMonograph
pref label:
  en: Cefditoren Pivoxil
  ja: セフジトレン ピボキシル
monograph id: JP18-cefditoren-pivoxil
publisher: JP
status: Official
version: 18
molecular formula: C25H28N6O7S3
molecular weight: 620.72
cas number: 117467-28-4
definition:
  en: Cefditoren Pivoxil contains not less than 770 mg (potency) and not more than 820 mg (potency) per mg, Optical rotation <2.
appearance:
  en: Cefditoren Pivoxil occurs as a light yellow-white to light yellow crystalline powder. It is sparingly soluble in methanol, slightly soluble in acetonitrile and in ethanol (95), very slightly soluble in diethyleter and practically insoluble in water. It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 5 mg of Cefditoren Pivoxil in 3 mL of hydroxylammonium chloride-ethanol TS, allow to stand for 5 minutes, add 1 mL of acidic ammonium iron (III) sulfate TS and shake: a red-brown color develops. Dissolve 1 mg of Cefditoren Pivoxil in 1 mL of dilute hydrochloric acid and 4 mL of water, add 3 drops of sodium nitrite TS under ice-cooling, shake, and allow to stand for 2 minutes. Then add 1 mL of ammonium amidosulfate TS, shake well, and allow to stand for 1 minute, and add 1 mL of N,N-diethyl-N?-1-naphthylethylenediamine oxalate TS: a purple color develops. Determine the absorption spectrum of a solution of Cefditoren Pivoxil in methanol (1 in 50,000) as directed MS: Amount [mg (potency)] of Cefditoren Pivoxil RS taken Internal standard solution—A solution of propyl p-hydrox-ybenzoate in acetonitrile (1 in 200). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 230 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 1.58 g of ammonium formate in 900 mL of water, adjust to pH 6.0 with diluted formic acid (1 in 250), and add water to make 1000 mL. To 450 mL of this solution add 275 mL of acetonitrile and 275 mL of methanol. Flow rate: Adjust so that the retention time of cefditoren pivoxil is about 15 minutes. ‌668‌ System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the internal standard and cefditoren pivoxil are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeated 5 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of cefditoren pivoxil to that of the intern…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cefditoren Pivoxil according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Being specified separately when the drug is granted approval based on the Law. Water <2.48> Not more than 1.5z (0.5 g, volumetric titra-tion, direct titration). Residue on ignition Being specified separately when the drug is granted approval based on the Law.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Conduct this procedure using light-resistant vessels. Weigh accurately an amount of Cefditoren Pivoxil and Cef-ditoren Pivoxil RS, equivalent to about 40 mg (potency), dis-solve in 40 mL of acetonitrile, add exactly 10 mL each of the internal standard solution, and add acetonitrile to make 100 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and calculate the ratios, QT and QS, of the peak area of cefditoren pivoxil to that of the internal standard. calculated on the anhydrous basis. The potency of Cefditoren Pivoxil is expressed as mass (potency) of cefditoren (C H N O S : 506.58). Amount [ mg (potency)] of cefditoren (C ＝ MS × QT/QS × 1000 19H18N6O5S3) 19 18 6 5 3 Description Cefditoren Pivoxil occurs as a light yellow-white to light yellow crystalline powder. It is sparingly soluble in methanol, slightly soluble in acetonitrile and in ethanol (95), very slightly soluble in diethyleter and practically insoluble in water. It dissolves in dilute hydrochloric acid. Identification (1) Dissolve 5 mg of Cefditoren Pivoxil in 3 mL of hydroxylammonium chloride-ethanol TS, allow to stand for 5 minutes, add 1 mL of acidic ammonium iron (III) sulfate TS and shake: a red-brown color develops. Dissolve 1 mg of Cefditoren Pivoxil in 1 mL of dilute hydrochloric acid and 4 mL of water, add 3 drops of sodium nitrite TS under ice-cooling, shake, and allow to stand for 2 minutes. Then add 1 mL of ammonium amidosulfate TS, shake well, and allow to stand for 1 minute, and add 1 mL of N,N-diethyl-N?-1-naphthylethylenediamine oxalate TS: a purple color develops. Determine the absorption spectrum of a solution of Cefditoren Pivoxil in methanol (1 in 50,000) as directed MS: Amount [mg (potency)] of Cefditoren Pivoxil RS taken Internal standard solution—A solution of propyl p-hydrox-ybenzoate in aceton…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cefepime-dihydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Cefepime Dihydrochloride Hydrate
  ja: セフェピム塩酸塩水和物
monograph id: JP18-cefepime-dihydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C19H24N6O5S2.2HCl.H2O
molecular weight: 571.5
cas number: 123171-59-5
definition:
  en: Cefepime Dihydrochloride Hydrate contains not less than 835 mg (potency) and not more than 886 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefepime Dihydrochloride Hydrate occurs as a white to yellowish white, crystals or crystalline powder. It is freely soluble in water and in methanol, and slightly soluble in ethanol (95), and practically in soluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.02 g of Cefepime Dihydro-chloride Hydrate in 2 mL of water, add 1 mL of a solution of hydroxylammonium chloride (1 in 10) and 2 mL of so-dium hydroxide TS, allow to stand for 5 minutes, then add 3 mL of 1 mol/L hydrochloric acid TS and 3 drops of iron (III) chloride TS: a red-brown color develops. Determine the absorption spectra of solutions (1 in 20,000) of Cefepime Dihydrochloride Hydrate and Cefepime Dihydrochloride RS as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare these spectra: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectra of Cefepime Dihydrochloride Hydrate and Cefepime Dihydro-chloride RS as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare these spectra: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefepime Dihydrochloride Hydrate in heavy water for nuclear mag-netic resonance spectroscopy (1 in 10) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using sodium 3-trimethylsilylpropionate-d4 for nuclear magnetic resonance spectroscopy as an internal reference compound: it exhibits single signals, A and B, at around d 3.1 ppm and at around d 7.2 ppm, respectively, and the ratio of integrated intensity of each signal, A:B, is about 3:1. Amount [mg (potency)] of cefditoren (C ＝ MS × QT/QS × 25 19H18N6O5S3) Dissolve 15 mg of Cefepime Dihydrochloride Hy-drate in 5 mL of water, and add 2 drops of silver nitrate TS: a white turbidity is produced. MS: Amount [mg (potency)] of Cefditoren Pivoxil RS 1 cm taken Absorbance <2.24> E 1z (259 nm): 310 – 340 (50 mg calcu- lated on the anhydrous basis, water, 1000 mL). Internal standard solution—A solution of propyl parahy- D Optical rotation <2.49> [a]20: ＋39 – ＋479(60 mg calcu-lated on the anhydrous basis, water, 20 mL, 100 mm). pH <2.54> Dissolve 0.1 g of Cefepi…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Cefepime Dihydrochloride Hydrate in 5 mL of a solution of L-arginine (3 in 50): the solution is clear and has no more color than Matching Fluid H. Heavy metals <1.07>—Proceed with 1.0 g of Cefepime Dihydrochloride Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). N-Methylpyrrolidine—Weigh accurately an amount of Cefepime Dihydrochloride Hydrate equivalent to about 80 mg (potency), dissolve in diluted nitric acid (2 in 3125) to make exactly 10 mL, and use this solution as the sample so-lution. Separately, put 30 mL of water in a 100-mL volumet-ric flask, weigh accurately the mass of flask, then add about 0.125 g of N-methylpyrrolidine, weigh accurately the mass of the flask again, and add water to make exactly 100 mL. Cefepime Dihydrochloride Hydrate in the mobile phase A to make 50 mL, and use this solution as the sample solution. Perform the test with 5 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine the area of each peak by the automatic integration method. Calculate the total amount of the peaks other than cefepime by the area percen-tage method: not more than 0.5z. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase A: Dissolve 0.57 g of ammonium dihydro-genphosphate in 1000 mL of water. Mobile phase B: Acetonitrile. Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. Pipet 4 mL of this solution, add diluted nitric acid (2 in 3125) to make exactly 100 mL, and use this solution as the standard…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefepime Dihydro-chloride Hydrate and Cefepime Dihydrochloride RS, equiva-lent to about 60 mg (potency), dissolve in the mobile phase to make exactly 50 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the JP XVIII Official Monographs / Cefepime Dihydrochloride for Injection 671 ‌test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of cefepime in each solution. Amount [ mg (potency)] of cefepime (C19H24N6O5S2) ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Cefepime Dihydrochloride RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 3.9 mm in inside diame-ter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Adjust a solution of sodium 1-pentanesul-fonate (261 in 100,000) to pH 3.4 with acetic acid (100), then adjust this solution to pH 4.0 with a solution of potassium hydroxide (13 in 20). To 950 mL of this solution add 50 mL of acetonitrile. Flow rate: Adjust so that the retention time of cefepime is about 8 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates of the peak of cefepime is not less than 1500. System repeatability: When the test is repeated 5 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak areas of cefepime is not more than 2.0z.
storage conditions:
  en: Containers—Hermetic containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cefixime-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Cefixime Hydrate
  ja: セフィキシム水和物
monograph id: JP18-cefixime-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C16H15N5O7S2.3H2O
molecular weight: 507.5
appearance:
  en: Cefixime Hydrate occurs as a white to light yellow crystalline powder. It is freely soluble in methanol and in dimethylsulfoxide, sparingly soluble in ethanol (99.5), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefixime Hydrate in 0.1 mol/L phosphate buffer solution (pH 7.0) (1 in 62,500) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefixime RS prepared in the same manner as the sample so-lution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cefixime Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Cefixime RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolve 50 mg of Cefixime Hydrate in 0.5 mL of a mixture of deuterated dimethylsulfoxide for nuclear mag-netic resonance spectroscopy and heavy water for nuclear magnetic resonance spectroscopy (4:1). Determine the 1H spectrum of this solution, as directed under Nuclear Mag-netic Resonance Spectroscopy <2.21>, using tetramethylsi-lane for nuclear magnetic resonance spectroscopy as an in-ternal reference compound: it exhibits a singlet signal A at around d 4.7 ppm, and a multiplet signal B between d 6.5 ppm and d 7.4 ppm. The ratio of integrated intensity of these signals, A:B, is about 1:1. Optical rotation <2.49> [a]20: －75 – －889(0.45 g calcu-lated on the anhydrous bases, a solution of sodium hydrogen carbonate (1 in 50), 50 mL, 100 mm). D
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Dissolve 0.1 g of Cefixime Hydrate in 100 mL of 0.1 mol/L phosphate buffer solution (pH 7.0), and use this solu-tion as the sample solution. Perform the test with 10 mL of the sample solution as directed under Liquid Chromatogra-phy <2.01> according to the following conditions. Determine each peak area by the automatic integration method, and calculate their amounts by the area percentage method: the amount of the peak other than cefixime is not more than 1.0z, and the total amount of the peaks other than cefixime is not more than 2.5z. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 3 times as long as the retention time of cefixime, beginning after the solvent peak. System suitability— Test for required detectability: To 1 mL of the sample so-lution add 0.1 mol/L phosphate buffer solution (pH 7.0) to make 100 mL, and use this solution as the solution for sys-tem suitability test. Pipet 1 mL of the solution for system suitability test, add 0.1 mol/L phosphate buffer solution (pH 7.0) to make exactly 10 mL. Confirm that the peak area of cefixime obtained with 10 mL of this solution is equivalent to 7 to 13z of that with 10 mL of the solution for system suitability test. System performance: When the procedure is run with 10 mL of the solution for system suitability test under the above operating conditions, the number of theoretical plates and the symmetry factor of the peak of cefixime are not less than 4000 and not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the solution for system suitability test under the above operating conditions, the relative standard devia-tion of the peak areas of cefixime is not more than 2.0z. Water <2.48> Not less than 9.0 and not more than 12.0z (0.1 g, volumetric titration, direct titration). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefixime Hydrate, equivalent to about 0.1 g (potency), and dissolve in 0.1 mol/L phosphate buffer solution (pH 7.0) to make exactly 100 mL. Pipet 10 mL of this solution, add 0.1 mol/L phos-phate buffer solution (pH 7.0) to make exactly 50 mL, and use this solution as the sample solution. Separately, weigh accurately an amount of Cefixime RS, equivalent to about 20 mg (potency), and dissolve in 0.1 mol/L phosphate buffer solution (pH 7.0) to make exactly 20 mL. Pipet 10 mL of this solution, add 0.1 mol/L phosphate buffer solution (pH 7.0) to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of cefixime in each solution. Amount [mg (potency)] of cefixime (C16H15N5O7S2) ＝ MS × AT/AS × 5000 MS: Amount [mg (potency)] of Cefixime RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). ‌JP XVIII Official Monographs / Cefixime Capsules 673 Column: A stainless steel column 4 mm in inside diameter and 125 mm in length, packed with octadecylsilanized silica gel for liquid chromatography (4 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: To 25 mL of a solution of tetrabutylammo-nium hydroxide TS (10 in 13) add water to make 1000 mL, and adjust to pH 6.5 with diluted phosphoric acid (1 in 10). To 300 mL of this solution add 100 mL of acetonitrile. Flow rate: Adjust so that the retention time of cefixime is about 10 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of cefixime are not less than 4000 and not more than 2.0, respectively. System repeatability: When th…
storage conditions:
  en: Containers—Hermetic containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cefmenoxime-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cefmenoxime Hydrochloride
  ja: セフメノキシム塩酸塩
monograph id: JP18-cefmenoxime-hydrochloride
publisher: JP
status: Official
version: 18
cas number: 75738-58-8
definition:
  en: Cefmenoxime Hydrochloride contains not less than 890 mg (potency) and not more than 975 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefmenoxime Hydrochloride occurs as white to light orange-yellow, crystals or crystalline powder. It is freely soluble in formamide and in dimethylsulfoxide, slightly soluble in methanol, very slightly soluble in water, and practically insoluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefmenoxime Hydrochloride in 0.1 mol/L phos-phate buffer solution (pH 6.8) (3 in 200,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefmenoxime Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cef-menoxime Hydrochloride as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cefmenoxime Hydrochloride RS: both spec-tra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cef- Amount [mg (potency)] of ceˆxime (C ＝ MS × AT/AS × 5 16H15N5O7S2) menoxime Hydrochloride in deuterated dimethylsulfoxide for nuclear magnetic resonance spectroscopy (1 in 10) as directed under Nuclear Magnetic Resonance Spectroscopy MS: Amount [mg (potency)] of Ceˆxime RS taken
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution ob-tained by dissolving 1.0 g of Cefmenoxime Hydrochloride in 10 mL of diluted sodium carbonate TS (1 in 4) is clear and colorless to light yellow. Heavy metals <1.07>—Proceed with 1.0 g of Cef- menoxime Hydrochloride according to Method 4, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Cefmenoxime Hydrochloride according to Method 4 and adding 10 mL of dilute hydrochloric acid to the residue after cooling, and perform the test (not more than 2 ppm). Related substances—Weigh accurately about 0.1 g of Cefmenoxime Hydrochloride, dissolve in 20 mL of 0.1 mol/L phosphate buffer solution (pH 6.8) and add the mobile phase to make exactly 100 mL. Pipet 4 mL of this solution, add the mobile phase to make exactly 50 mL, and use this solution as the sample solution. Separately, weigh accurately about 10 mg of 1-methyl-1H-tetrazol-5-thiol, and dissolve in the mobile phase to make exactly 100 mL. Pipet 4 mL of this solution, add the mobile phase to make exactly 250 mL, and use this solution as the standard solution (1). Weigh accurately about 0.1 g of Cefmenoxime Hydrochlo-ride RS, dissolve in 20 mL of 0.1 mol/L phosphate buffer solution (pH 6.8) and add the mobile phase to make exactly 100 mL. Pipet 1 mL of this solution, add the mobile phase to make exactly 250 mL, and use this solution as the standard solution (2). Perform the test immediately after preparation of these solutions with exactly 10 mL each of the sample solution and standard solutions (1) and (2) as directed under Liquid Chromatography <2.01> according to the following the standard solution (1), add the mobile phase to make exactly 100 mL. Confirm that the peak area of 1-methyl-1H-tetrazol-5-thiol obtained with 10 mL of this solution is equivalent to 4.5 to 5.5z of that with 10 mL of the standard solution (1). Then, measure exactly 2 mL of the sta…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefmenoxime Hy-drochloride and Cefmenoxime Hydrochloride RS, equiva-lent to about 50 mg (potency), dissolve each in 10 mL of 0.1 mol/L phosphate buffer solution (pH 6.8) and add the mobile phase to make exactly 50 mL. Pipet 4 mL each of these solutions, add exactly 20 mL of the internal standard solution and the mobile phase to make 50 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi-tions, and calculate the ratios, QT and QS, of the peak area of cefmenoxime to that of the internal standard. conditions. Determine each peak area of these solutions by the automatic integration method, and calculate the amounts of 1-methyl-1H-tetrazol-5-thiol and the total related sub- Amount [ mg (potency)] of cefmenoxime (C ＝ MS × QT/QS × 1000 16H17N9O5S3) stance by the following formula: the amount of 1-methyl-1H-tetrazol-5-thiol is not more than 1.0z, and the total related substance is not more than 3.0z. Amount (z) of 1-methyl-1H-tetrazol-5-thiol ＝ MSa/MT × ATa/ASa × 20 Amount (z) of total related substances MS: Amount [mg (potency)] of Cefmenoxime Hydrochlo-ride RS taken Internal standard solution—A solution of phthalimide in methanol (3 in 2000). Operating conditions— Detector: An ultraviolet absorption photometer (wave- ＝ MSa/MT × ATa/ASa × 20 length: 254 nm). Column: A stainless steel column 4 mm in inside diameter ＋ MSb/MT × ST/ASb × 5 MSa: Amount (g) of 1-methyl-1H-tetrazol-5-thiol taken MSb: Amount (g) of Cefmenoxime Hydrochloride RS taken MT: Amount (g) of Cefmenoxime Hydrochloride taken ASa: Peak area of 1-methyl-1H-tetrazol-5-thiol from the standard solution (1) ASb: Peak area of cefmenoxime from the standard solu-tion (2) ATa: Peak area of 1-methyl-1H-tetrazol-5-thiol from the sample solution ST: Total area of the peaks other than 1-methyl-1H-…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cefotetan
type: ChemicalDrugMonograph
pref label:
  en: Cefotetan
  ja: セフォテタン
monograph id: JP18-cefotetan
publisher: JP
status: Official
version: 18
molecular formula: C17H17N7O8S4
molecular weight: 575.62
cas number: 69712-56-7
definition:
  en: Cefotetan contains not less than 960 mg (potency) and not more than 1010 mg (potency) per mg, calcu-lated on the anhydrous basis.
appearance:
  en: Cefotetan occurs as white to light yellow-white powder. It is sparingly soluble in methanol, and slightly soluble in water and in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefotetan in phosphate buffer solution for anti-biotics, pH 6.5 (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefotetan RS prepared in the same manner as the sample so- than 0.4z. 1-Methyl-1H-tetrazole-5-thiol (z) lution: both spectra exhibit similar intensities of absorption at the same wavelengths. ＝ MSa/MT × QTa/QSa × 1/100 Determine the infrared absorption spectrum of Cefotetan as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cefotetan RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. Dissolve 50 mg of Cefotetan in 0.5 mL of a solution of sodium hydrogen carbonate in heavy water for nuclear Cefotetan lactone (z) ＝ MSb/MT × QTb/QSb × 1/100 D2-Cefotetan (z) ＝ MSb/MT × QTc/QSb × 1/100 Isothiazole substance (z) ＝ MSb/MT × QTd/QSb × 1/100 Each of other related substances (z) magnetic resonance spectroscopy (1 in 25). Determine the 1H spectrum of this solution as directed under Nuclear Magnetic ＝ MSb/MT × QTe/QSb × 1/100 Resonance Spectroscopy <2.21>, using sodium 3-trimethyl- silylpropanesulfonate for nuclear magnetic resonance spec-troscopy as an internal reference compound: it exhibits singlet signals, A, B, C and D, at around d 3.6 ppm, at around d 4.0 ppm, at around d 5.1 ppm and at around d 5.2 ppm, respectively. The ratio of the integrated intensity of each signal, A:B:C:D, is about 3:3:1:1. D Optical rotation <2.49> [a]20: ＋112 – ＋1249(0.5 g calcu-lated on the anhydrous basis, a solution of sodium hydrogen carbonate (1 in 200), 50 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Cefotetan in 10 mL of a solution of sodium hydrogen car-bonate (1 in 30): the solution is clear, and colorless or light yellow. Heavy metals <1.07>—Proceed with 1.0 g of Cefote- tan according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Weigh accurately about 0.1 g of Cefotetan, dissolve in a suitable amount of methanol, add exactly 2 mL of the internal standard solution and methanol to make 20 mL, and use this solution as the sample solution. Separately, weigh accurately about 3 mg of 1-methyl-1H-tetrazole-5-thiol for liquid chromatography, previously dried in a desiccator (in vacuum, silica gel) for 2 hours, and about 2 mg of Cefotetan RS, calculated on the anhydrous basis, dissolve in methanol to make exactly 20 mL. Pipet 2 mL of this solution, add exactly 2 mL of the internal standard solu-tion and methanol to make 20 mL, and use this solution as the standard solution. Perform the test with 5 mL of the sam-ple solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi-tions, and calculate the ratios, QTa, QTb, QTc, QTd, QTe and QTf, of the peak areas of 1-methyl-1H-tetrazole-5-thiol, cefotetan lactone having the relative retention time of about 0.5 to cefotetan, D2-cefotetan having the relative retention time of about 1.2, isothiazole substance having the relative retention time of about 1.3, each of other related substances and the total of other related substances, to the peak area of the internal standard, respectively, obtained from the sample solution, and the ratios, QSa and QSb, of the peak areas of 1-methyl-1H-tetrazole-5-thiol and cefotetan, to the peak area of the internal standard, respectively, from the standard so-lution. Calculate the amount of 1-methyl-1H-tetrazole-5-thiol, cefotetan lactone, D2-cefotetan, isothiazole substance, each of other rela…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefotetan and Cefotetan RS, equivalent to about 50 mg (potency), and dis-solve each in phosphate buffer solution for antibiotics, pH 6.5 to make exactly 50 mL. Pipet 15 mL each of these solu-tions, add exactly 10 mL of the internal standard solution and phosphate buffer solution for antibiotics, pH 6.5 to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of cefotetan to that of the internal standard. Amount [ mg (potency)] of cefotetan (C17H17N7O8S4) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Cefotetan RS taken Internal standard solution—A solution of anhydrous caffeine (1 in 1000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 11.53 g of phosphoric acid in 1000 mL of water. To 850 mL of this solution add 50 mL of acetonitrile, 50 mL of acetic acid (100) and 50 mL of metha-nol. Flow rate: Adjust so that the retention time of cefotetan is about 17 minutes. System suitability— System performance: When the procedure is run with 5 mL of the standard solution under the above operating condi-tions, the internal standard and cefotetan are eluted in this order with the resolution between these peaks being not less than 8. System repeatability: When the test is repeated 5 times with 5 mL of the standard solution under the above operating conditions, the relative standard deviation of the ratio of the peak area of cefotetan to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cefotiam-hexetil-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cefotiam Hexetil Hydrochloride
  ja: セフォチアム ヘキセチル塩酸塩
monograph id: JP18-cefotiam-hexetil-hydrochloride
publisher: JP
status: Official
version: 18
cas number: 95789-30-3
definition:
  en: Cefotiam Hexetil Hydrochloride contains not less than 615 mg (potency) and not more than 690 mg (po-tency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefotiam Hexetil Hydrochloride occurs as a white to light yellow powder. It is very soluble in water, in methanol and in ethanol (95), freely soluble in dimethylsulfoxide, and slightly soluble in acetonitrile. It dissolves in 0.1 mol/L hydrochloric acid TS. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefotiam Hexetil Hydrochloride in 0.1 mol/L hydrochloric acid TS (3 in 125,000) as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefotiam Hexetil Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the 1H spectrum of a solution of Cefotiam Hexetil Hydrochloride in deuterated dimethylsulfoxide for nuclear magnetic resonance spectroscopy (1 in 20) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using tetramethylsilane for nuclear magnetic resonance spec-troscopy as an internal reference compound: it exhibits two singlet signals, A and B, at around d 2.8 ppm and at around d 6.6 ppm, and a multiplet signal, C, at around d 6.9 ppm. The ratio of the integrated intensity of each signal, A:B:C, is about 6:1:1. To a solution of Cefotiam Hexetil Hydrochloride (1 in 200) add 2 mL of dilute nitric acid and 1 mL of silver nitrate TS, and mix: a white precipitate is formed. D Optical rotation <2.49> [a]20: ＋52 – ＋609(0.1 g calculated on the anhydrous basis, 0.1 mol/L hydrochloric acid TS, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cefotiam Hexetil Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 2.0 g of Cefotiam Hexetil Hydrochloride according to Method 3, and perform the test, using a solution of magnesium nitrate hexahydrate in ethanol (95) (1 in 5) (not more than 1 ppm). Related substance 1—Weigh accurately about 50 mg of Cefotiam Hexetil Hydrochloride, and dissolve in a mix-ture of diluted phosphoric acid (1 in 100) and acetonitrile (4:1) to make exactly 50 mL. Pipet 10 mL of this solution, add a mixture of diluted phosphoric acid (1 in 100) and acetonitrile (4:1) to make exactly 25 mL, and use this solu-tion as the sample solution. Separately, weigh accurately about 50 mg of Cefotiam Hexetil Hydrochloride RS, and dissolve in a mixture of diluted phosphoric acid (1 in 100) and acetonitrile (4:1) to make exactly 50 mL. Pipet 1 mL of this solution, add a mixture of diluted phosphoric acid (1 in 100) and acetonitrile (4:1) to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and determine each peak area by the automatic integration method. Calculate the amount of the related substances by the following equa-tion: the amount of the related substance having the relative retention time of about 1.2 to one of the peaks of cefotiam hexetil, which has the larger retention time, is not more than 2.0z, and each amount of the other related substances is not more than 0.5z. For the peak area, having the relative retention time of about 1.2 to one of the peaks of cefotiam hexetil, which has the larger retention time, multiply the cor-rection factor, 0.78. Amount (z) of related substance ＝ MS/MT × AT/AS × 5 System performanc…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefotiam Hexetil Hydrochloride and Cefotiam Hexetil Hydrochloride RS, equivalent to about 30 mg (potency), and dissolve each in a mixture of diluted phosphoric acid (1 in 100) and acetonitrile (4:1) to make exactly 50 mL. Measure exactly 5 mL each of these solutions, add exactly 5 mL of the internal standard solution and a mixture of diluted phosphoric acid (1 in 100) and acetonitrile (4:1) to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of cefotiam hexetil to that of the internal standard. For this calculation, the total of the areas of the two peaks appeared closely each other at the retention time of around 10 minutes is used as the peak area of cefotiam hexetil. ing conditions, the relative standard deviation of the ratios of the peak area of cefotiam hexetil to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cefotiam-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cefotiam Hydrochloride
  ja: セフォチアム塩酸塩
monograph id: JP18-cefotiam-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C18H23N9O4S3.2HCl
molecular weight: 598.55
cas number: 66309-69-1
definition:
  en: Cefotiam Hydrochloride contains not less than 810 mg (potency) and not more than 890 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefotiam Hydrochloride occurs as white to light yellow, crystals or crystalline powder. It is freely soluble in water, in methanol and in for-mamide, slightly soluble in ethanol (95), and practically in-soluble in acetonitrile. Amount [ mg (potency)] of cefotiam (C ＝ MS × QT/QS × 1000 18H23N9O4S3)
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefotiam Hydrochloride (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and MS: Amount [mg (potency)] of Cefotiam Hexetil Hydro-chloride RS taken Internal standard solution—A solution of benzoic acid in a mixture of diluted phosphoric acid (1 in 100) and acetonitrile (4:1) (7 in 10,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of diluted 0.2 mol/L potassium dihydrogen phosphate TS (1 in 2), acetonitrile and acetic acid (100) (72:28:1). Flow rate: Adjust so that the retention time of the faster peak of cefotiam hexetil is about 9 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the internal standard and cefotiam hexetil are eluted in this order with the resolution between the two peaks of cefotiam hexetil being not less than 2.0. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat- compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefotiam Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cefotiam Hydrochloride as directed in the potassium chlo-ride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cefotiam Hydrochloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefotiam Hydrochloride in h…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Cefotiam Hydrochloride in 10 mL of water: the solution is clear, and colorless to yellow. Heavy metals <1.07>—To 1.0 g of Cefotiam Hydro- chloride add 1 mL of sulfuric acid, and heat gently to car-bonize. After cooling, add 10 mL of a solution of magne-sium nitrate hexahydrate in ethanol (95) (1 in 10), fire the ethanol to burn, then heat gradually to incinerate. If a car-bonized residue still retains, moisten the residue with a little amount of sulfuric acid, and ignite again to incinerate. After cooling, add 2 mL of hydrochloric acid to the residue, heat on a water bath to dissolve, then heat to dryness. Add 10 mL of water, and heat to dissolve. After cooling, add ammonia TS dropwise to adjust to pH 3 – 4, if necessary, filter, wash the residue on the filter with 10 mL of water, transfer the fil-trate and washings into a Nessler tube, add water to make 50 mL, and use this solution as the test solution. Prepare the control solution with 2.0 mL of Standard Lead Solution in the same manner as for preparation of the test solution (not more than 20 ppm). Arsenic <1.11>—Incinerate 1.0 g of Cefotiam Hydro- chloride according to Method 4. After cooling, add 10 mL of dilute hydrochloric acid to the residue, heat to dissolve on the water bath, and use this solution as the test solution. Per-form the test (not more than 2 ppm). Water <2.48> Not more than 7.0z (0.25 g, volumetric titration, direct titration. Use a mixture of formamide for water determination and methanol for water determination (2:1) instead of methanol for water determination).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefotiam Hydro-chloride and Cefotiam Hydrochloride RS, equivalent to about 0.1 g (potency), and dissolve each in the mobile phase to make exactly 100 mL, and use these solutions as the sam-ple solution and the standard solution, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of cefotiam in each solution. Amount [ mg (potency)] of cefotiam (C18H23N9O4S3) ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Cefotiam Hydrochloride RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.0 mm in inside diame-ter and 125 mm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diame-ter). Column temperature: A constant temperature of about 259C. Mobile phase: To 800 mL of 0.05 mol/L disodium hydrogenphosphate TS add 0.05 mol/L potassium dihydro-genphosphate TS to adjust the pH to 7.7. To 440 mL of this solution add 60 mL of acetonitrile. Flow rate: Adjust so that the retention time of cefotiam is about 14 minutes. System suitability— System performance: Dissolve 0.04 g of orcine in 10 mL of the standard solution. When the procedure is run with 10 mL of the standard solution under the above operating condi-tions, orcine and cefotiam are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak areas of cefotiam is not more than 1.0z.
storage conditions:
  en: Containers—Hermetic containers.
type: PharmacopoeiaMonograph

cefozopran-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cefozopran Hydrochloride
  ja: セフォゾプラン塩酸塩
monograph id: JP18-cefozopran-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C19H17N9O5S2.HCl
molecular weight: 551.99
definition:
  en: Cefozopran Hydrochloride contains not less than 860 mg (potency) and not more than 960 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefozopran Hydrochloride occurs as white to pale yellow, crystals or crystalline powder. It is freely soluble in dimethylsulfoxide and in formamide, slightly soluble in water, in methanol and in ethanol (95), and practically insoluble in acetonitrile and diethyleter.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.02 g of Cefozopran Hydro-chloride in 10 mL of water, add 1 mL of a solution of hy-droxylammonium chloride (1 in 10) and 2 mL of sodium hy-droxide TS, allow to stand for 5 minutes, then add 3 mL of 1 mol/L hydrochloric acid TS and 3 drops of iron (III) chlo-ride TS, and mix: a red-purple color develops. Determine the absorption spectra of solutions of Cefozopran Hydrochloride and Cefozopran Hydrochloride RS in a mixture of sodium chloride TS and methanol (3:2) (1 in 100,000) as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare these spectra: both spectra exhibit similar intensities of absorption at the same wave-lengths. Determine the 1H spectrum of a solution of Cefozopran Hydrochloride in deuterated dimethylsulfoxide for nuclear magnetic resonance spectroscopy (1 in 20) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using tetramethylsilane for nuclear magnetic reso- nance spectroscopy as an internal reference compound: it exhibits a singlet signal A at around d 3.9 ppm, a doublet signal B at around d 5.2 ppm, and a quartet signal C at around d 8.0 ppm, and the ratio of integrated intensity of each signal, A:B:C, is about 3:1:1. Dissolve 0.01 g of Cefozopran Hydrochloride in 1 mL of water and 2 mL of acetic acid (100), add 2 drops of silver nitrate TS, and mix: a white turbidity is formed. 1 cm Absorbance <2.24> E 1z (238 nm): 455 – 485 (50 mg calcu-lated on the anhydrous basis, a mixture of sodium chloride TS and methanol (3:2), 5000 mL). D Optical rotation <2.49> [a]20: －73 – －789(0.1 g calculated on the anhydrous basis, a mixture of sodium chloride TS and methanol (3:2), 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Being specified separately when the drug is granted approval based on the Law. Heavy metals <1.07>—Proceed with 2.0 g of Cefozopran Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic—Being specified separately when the drug is granted approval based on the Law. Related substances—Being specified separately when the drug is granted approval based on the Law. Water <2.48> Not more than 2.5z (0.5 g, volumetric titra-tion, direct titration. Use a mixture of formamide for water determination and methanol for water determination (2:1) instead of methanol for water determination). Residue on ignition Being specified separately when the drug is granted approval based on the Law. Bacterial endotoxins <4.01> Less than 0.05 EU/mg (po-tency).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefozopran Hydro-chloride and Cefozopran Hydrochloride RS, equivalent to about 50 mg (potency), and dissolve each in the mobile phase to make exactly 50 mL. Pipet 10 mL each of these solutions, add exactly 10 mL of the internal standard solution and the mobile phase to make 25 mL, and use these solutions as the sample solution and the standard solution, respectively. Per-form the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of cefozopran to that of the internal standard. Amount [ mg (potency)] of cefozopran (C19H17N9O5S2) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Cefozopran Hydrochlo-ride RS taken Internal standard solution—A solution of 2,4-dihydroxyben-zoic acid in the mobile phase (1 in 1250). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Mix 0.366 g of diethylamine with water to make 1000 mL, and add 60 mL of acetonitrile and 5 mL of acetic acid (100). Flow rate: Adjust so that the retention time of cefozopran ‌692‌ is about 9 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, cefozopran and the internal standard are eluted in this order with the resolution between these peaks being not less than 10. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of cefozopran to that of the internal stand-ard is not more than 1.0z.
storage conditions:
  en: Containers—Hermetic containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cefpirome-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Cefpirome Sulfate
  ja: セフピロム硫酸塩
monograph id: JP18-cefpirome-sulfate
publisher: JP
status: Official
version: 18
molecular formula: C22H22N6O5S2.H2SO4
molecular weight: 612.66
definition:
  en: Cefpirome Sulfate contains not less than 760 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefpirome Sulfate occurs as a white to pale yellow-white crystalline powder, and has a slight, character-istic odor. It is soluble in water, and practically insoluble in ethanol (95) and in diethyl ether. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 10 mg of Cefpirome Sulfate in 2 mL of water, add 3 mL of hydroxylammonium hydrochlo-ride-ethanol TS, allow to stand for 5 minutes, add 1 mL of acidic ammonium iron (III) sulfate TS, and shake: a red-brown color develops. Dissolve 1 mg of Cefpirome Sulfate in 4 mL of water, add 1 mL of dilute hydrochloric acid while cooling in ice, add 1 mL of a freshly prepared solution of sodium nitrite (1 in 100), and allow to stand for 2 minutes. Add 1 mL of am-monium amidosulfuric acid TS while cooling in ice bath, allow to stand for 1 minute, and add 1 mL of a solution of lated on the anhydrous basis, 0.01 mol/L hydrochloric acid TS, 2500 mL). D Optical rotation <2.49> [a]20: －27 – －339(50 mg calcu-lated on the anhydrous basis, a solution prepared by addi-tion of water to 25 mL of acetonitrile to make 50 mL, 20 mL, 100 mm). pH <2.54> Dissolve 0.1 g of Cefpirome Sulfate in 10 mL of water: the pH of the solution is between 1.6 and 2.6.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Being specified separately when the drug is granted approval based on the Law. Heavy metals <1.07>—Proceed with 1.0 g of Cefpi- rome Sulfate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic—Being specified separately when the drug is granted approval based on the Law. Related substances—Being specified separately when the drug is granted approval based on the Law. Water <2.48> Not more than 2.5z (0.5 g, volumetric titra-tion, direct titration). Residue on ignition Being specified separately when the drug is granted approval based on the Law. Bacterial endotoxins <4.01> Less than 0.10 EU/mg (po-tency).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefpirome Sulfate and Cefpirome Sulfate RS, equivalent to about 50 mg (po-tency), dissolve each in water to make exactly 100 mL. Pipet 5 mL of these solutions, add each in water to make exactly 20 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly 20 mL of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of cefpirome in each solution. N-1-naphthylethylene dihydrochloride (1 in 1000): a purple color develops. Take 5 mg of Cefpirome Sulfate, dissolve in 1 mL of Amount [ mg (potency)] of cefpirome (C ＝ MS × AT/AS × 1000 22H22N6O5S2) ethanol (95) and 1 mL of water, add 100 mg of 1-chloro-2,4-dinitrobenzene, and heat on a water bath for 5 minutes. After cooling, add 2 or 3 drops of a solution of sodium hy-droxide (1 in 10) and 3 mL of ethanol (95): a red-brown color develops. MS: Amount [mg (potency)] of Cefpirome Sulfate RS taken ‌JP XVIII Official Monographs / Cefpodoxime Proxetil 695 Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 270 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 3.45 g of ammonium dihydrogen-phosphate in 1000 mL of water, and adjust the pH to 3.3 with phosphoric acid. To 800 mL of this solution add 100 mL of acetonitrile. Flow rate: Adjust so that the retention time of cefpirome is about 7.5 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theoretical plates of the peak of cefpi-rome is not less than 3600. System repeatability: When the test is repeated 5 times with 20 mL of the standard so…
storage conditions:
  en: Containers—Hermetic containers. Storage—At a temperature between 29C and 89C.
type: PharmacopoeiaMonograph

cefpodoxime-proxetil
type: ChemicalDrugMonograph
pref label:
  en: Cefpodoxime Proxetil
  ja: セフポドキシム プロキセチル
monograph id: JP18-cefpodoxime-proxetil
publisher: JP
status: Official
version: 18
molecular formula: C21H27N5O9S2
molecular weight: 557.6
cas number: 87239-81-4
definition:
  en: Cefpodoxime Proxetil contains not less than 706 mg (potency) and not more than 774 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefpodoxime Proxetil occurs as a white to light brown-white powder. It is very soluble in acetonitrile, in methanol and in chlo-roform, freely soluble in ethanol (99.5), and very slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefpodoxime Proxetil in acetonitrile (3 in 200,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of a solution of Cefpodoxime Proxetil RS prepared in the same manner as the sample solu-tion: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cef- podoxime Proxetil as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Cefpodoxime Proxetil RS: both spectra exhibit simi-lar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cef-podoxime Proxetil in deuterochloroform for nuclear mag-netic resonance spectroscopy (1 in 10) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using tetramethylsilane for nuclear magnetic resonance spectros-copy as an internal reference compound: it exhibits doublet signals, A and B, at around d 1.3 ppm and at around d 1.6 ppm, and singlet signals, C and D, at around d 3.3 ppm and at around d 4.0 ppm. The ratio of the integrated intensity of these signals, A:B:C:D, is about 2:1:1:1. D Optical rotation <2.49> [a]20: ＋24.0 – ＋31.49(0.1 g calcu-lated on the anhydrous basis, acetonitrile, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Cefpodoxime Proxetil according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 50 mg of Cefpodoxime Proxetil in 50 mL of a mixture of water, acetonitrile and acetic acid (100) (99:99:2), and use this solution as the sam-ple solution. Perform the test with 20 mL of the sample solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions. Determine each peak area by the automatic integration method, and calculate the amounts of them by the area percentage method: the amount of the peak, having the relative retention time of about 0.8 to the isomer B of cefpodoxime proxetil, is not more than 2.0z, the amount of the peak other than cefpodoxime proxetil is not more than 1.0z, and the total amount of the peaks other than cefpodoxime proxetil is not more than 6.0z. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 229C. Mobile phase A: A mixture of water, methanol and a solution of formic acid (1 in 50) (11:8:1). Mobile phase B: A mixture of methanol and a solution of formic acid (1 in 50) (19:1). Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. Time after injection Mobile phase A Mobile phase B of sample (min) (volz) (volz) 0 – 65 95 5 65 – 145 95 → 15 5 → 85 145 – 155 15 85 Flow rate: 0.7 mL per minute (the retention time of the isomer B of cefpodoxime proxetil is about 60 minutes). Time span of measurement: For 155 minutes after injec-tion, beginning after the solvent peak. System suitability— Test for required detectability: To 5 mL of the sample …
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cefroxadine-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Cefroxadine Hydrate
  ja: セフロキサジン水和物
monograph id: JP18-cefroxadine-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C16H19N3O5S.2H2O
molecular weight: 401.43
definition:
  en: Cefroxadine Hydrate contains not less than 930 mg (potency) and not more than 1020 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Cefroxadine Hydrate occurs as pale yellow-white to light yellow, crystalline particles or powder. It is very soluble in formic acid, slightly soluble in water and in methanol, and very slightly soluble in acetonitrile and in ethanol (95). It dissolves in 0.001 mol/L hydrochloric acid TS and in dilute acetic acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefroxadine Hydrate in 0.001 mol/L hydrochlo-ric acid TS (1 in 50,000) as directed under Ultraviolet-visible JP XVIII Official Monographs / Cefroxadine Hydrate 699 Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefroxadine RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorp-tion at the same wavelengths. Determine the infrared absorption spectrum of Cefroxadine Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cefroxadine RS: both spectra exhibit similar in-tensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefroxa-dine Hydrate in deuterated formic acid for nuclear magnetic resonance spectroscopy (1 in 10) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using tetramethyl-silane for nuclear magnetic resonance spectroscopy as an internal reference compound: it exhibits three sharp singlet signals, A, B and C, at around d 2.8 ppm, at around d 4.1 ppm and at around d 6.3 ppm. The ratio of the integrated intensity of each signal, A:B:C, is about 4:3:1. D Optical rotation <2.49> [a]20: ＋95 – ＋1089(0.1 g calcu-lated on the anhydrous basis, diluted acetic acid (100) (3 in 25), 100 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Weigh 1.0 g of Cefroxa-dine Hydrate in a porcelain crucible, add 10 mL of a solu-tion of magnesium nitrate hexahydrate in ethanol (95) (1 in 10), mix, burn the ethanol, and carbonize by gently heating. After cooling, add 2 mL of nitric acid, heat carefully, and incinerate by ignition at 500 – 6009C. If a carbonized sub-stance still remains, moisten it with a small amount of nitric acid, and incinerate again by ignition. After cooling, add 6 mL of hydrochloric acid, and evaporate on a water bath to dryness. Moisten the residue with 3 drops of hydrochloric acid, and add 10 mL of hot water to dissolve the residue by heating on a water bath. After cooling, adjust the pH be-tween 3 and 4 with ammonia TS, add 2 mL of dilute acetic acid, filter if necessary, transfer to a Nessler tube, wash the crucible with 10 mL of water, and add the washing and water to the tube to make 50 mL. Perform the test with this solution. Prepare the control solution as follows: Put 2.0 mL of Standard Lead Solution and 10 mL of a solution of mag- Column: A stainless steel column 4.6 mm in inside diame-ter and 10 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 1.4 g of sodium perchlorate in 1000 mL of a mixture of water and acetonitrile (489:11). Flow rate: Adjust so that the retention time of cefroxadine is about 20 minutes. Time span of measurement: About 2 times as long as the retention time of cefroxadine. System suitability— Test for required detectability: Measure exactly 2 mL of the standard solution, and add the mobile phase to make ex-actly 20 mL. Confirm that the peak area of cefroxadine ob-tained with 40 mL of this solution is equivalent to 7 to 13z of that with 40 mL of the standard solution. System performance: Dissolve 3 mg of Cefroxadine Hy-drate and 15 mg of orcin in 100 mL of the mobile phase. When the procedure is…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefroxadine Hy-drate and Cefroxadine RS, equivalent to about 50 mg (po-tency), dissolve each in a suitable amount of a mixture of dilute acetic acid and phosphoric acid (500:1), add exactly 5 mL of the internal standard solution and a mixture of dilute acetic acid and phosphoric acid (500:1) to make 200 mL, and use these solutions as the sample solution and standard solu-tion. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and cal-culate the ratios, QT and QS, of the peak area of cefroxadine to that of the internal standard. nesium nitrate hexahydrate in ethanol (95) (1 in 10) in a por-celain crucible, and proceed as directed for the preparation of the test solution (not more than 20 ppm). Amount [ mg (potency)] of cefroxadine (C ＝ MS × QT/QS × 1000 16H19N3O5S) (2) Related substances—Dissolve 10 mg of Cefroxadine Hydrate in 100 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with ex-actly 40 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and determine each peak area by the automatic integration method: the areas of the peaks, having the relative retention times of about 0.07, about 0.6 and about 0.8 to cefroxadine obtained from the sample solution are not larger than 2 times, 4 times and 1 time the peak area of cefroxadine from the standard solu-tion, respectively, and any peak area other than cefroxadine and other than the peaks mentioned above is not larger than 1/2 times the peak area of cefroxadine from the standard so-lution, and the total area of the peaks other than cefroxadine is not larger than 6 times the peak area of cefroxadine from the standard solutio…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

ceftazidime-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Ceftazidime Hydrate
  ja: セフタジジム水和物
monograph id: JP18-ceftazidime-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C22H22N6O7S2.5H2O
molecular weight: 636.65
cas number: 78439-06-2
definition:
  en: Ceftazidime Hydrate contains not less than 950 mg (potency) and not more than 1020 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Ceftazidime Hydrate occurs as a white to light yellow-white crystalline powder. It is slightly soluble in water, and very slightly soluble in acetonitrile and in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Ceftazidime Hydrate in phosphate buffer solu-tion (pH 6.0) (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Ceftazidime RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorp-tion at the same wavelengths. Determine the infrared absorption spectrum of Ceftazidime Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Ceftazidime RS: both spectra exhibit similar in-tensities of absorption at the same wave numbers. To 0.05 g of Ceftazidime Hydrate add 5 mg of dried sodium carbonate, and add 0.5 mL of heavy water for nuclear magnetic resonance spectroscopy to dissolve. Deter-mine the 1H spectrum of this solution as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using so-dium 3-trimethylsilylpropanesulfonate for nuclear magnetic resonance spectroscopy as an internal reference compound: it exhibits singlet signals, A and B, at around d 1.5 ppm and at around d 6.9 ppm, and a multiplet signal C between d 7.9 ppm and d 9.2 ppm. The ratio of integrated intensity of each signal, A:B:C, is about 6:1:5. D Optical rotation <2.49> [a]20: －28 – －349(0.5 g calculated on the anhydrous basis, phosphate buffer solution (pH 6.0), 100 mL, 100 mm). pH <2.54> Dissolve 0.5 g of Ceftazidime Hydrate in 100 mL of water: the pH of the solution is between 3.0 and 4.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Ceftazidime Hydrate in 10 mL of a solution obtained by dissolving 5 g of anhydrous disodium hydrogen phosphate and 1 g of potassium dihydrogen phosphate in water to make 100 mL: the solution is clear, and its absorbance at 420 nm, determined as directed under Ultraviolet-visible Spectropho-tometry <2.24>, is not more than 0.20. JP XVIII Official Monographs / Ceftazidime Hydrate 703 Heavy metals <1.07>—Proceed with 1.0 g of Ceftazi-dime Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances (i) Trityl-t-butyl substance and t-butyl substance—Dissolve 0.10 g of Ceftazidime Hydrate in 2 mL of diluted disodium hydrogen phosphate TS (1 in 3), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add diluted disodium hydrogen-phosphate TS (1 in 3) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 2 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop with a mixture of acetic acid (100), n-butyl acetate, acetate buffer solution (pH 4.5) and 1-butanol (16:16:13:3) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots which appear upper in posi-tion than the principal spot obtained from the sample solu-tion are not more intense than the spot from the standard so-lution. (ii) Other related substances—Dissolve 20 mg of Ceftazi-dime Hydrate in 10 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample so-lution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 5 mL each of the sample solution and standard solution…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Ceftazidime Hy-drate, equivalent to about 0.1 g (potency), and dissolve in 0.05 mol/L phosphate buffer solution (pH 7.0) to make ex-actly 100 mL. Pipet 10 mL of this solution, add exactly 5 mL of the internal standard solution, then add 0.05 mol/L phos-phate buffer solution (pH 7.0) to make 50 mL, and use this solution as the sample solution. Separately, weigh accurately an amount of Ceftazidime RS, equivalent to about 20 mg (potency), dissolve in 0.05 mol/L phosphate buffer solution (pH 7.0) to make exactly 20 mL. Pipet 10 mL of this solu-tion, add exactly 5 mL of the internal standard solution, then add 0.05 mol/L phosphate buffer solution (pH 7.0) to make 50 mL, and use this solution as the standard solution. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of ceftazidime to that of the internal standard. ‌704‌ Amount [mg (potency)] of ceftazidime (C22H22N6O7S2) ＝ MS × QT/QS × 5000 MS: Amount [mg (potency)] of Ceftazidime RS taken Internal standard solution—A solution of dimedon in 0.05 mol/L phosphate buffer solution (pH 7.0) (11 in 10,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 10 cm in length, packed with hexasilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 4.26 g of anhydrous disodium hydrogen phosphate and 2.72 g of potassium dihydrogen phosphate in 980 mL of water, and add 20 mL of aceto-nitrile. Flow rate: Adjust so that the retention time of ceftazidime is about 4 minutes. System suitability— System performance: When the procedure is run with 5 mL of the standard solution under the above operating condi-tions, the internal standard and cef…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cefteram-pivoxil
type: ChemicalDrugMonograph
pref label:
  en: Cefteram Pivoxil
  ja: セフテラム ピボキシル
monograph id: JP18-cefteram-pivoxil
publisher: JP
status: Official
version: 18
molecular formula: C22H27N9O7S2
molecular weight: 593.64
definition:
  en: Cefteram Pivoxil contains not less than 743 mg (po-tency) and not more than 824 mg (potency) per mg, JP XVIII Official Monographs / Cefteram Pivoxil 705 calculated on the anhydrous basis.
appearance:
  en: Cefteram Pivoxil occurs as a white to pale yellow-white powder. It is very soluble in acetonitrile, freely soluble in metha-nol, in ethanol (95) and in chloroform, and practically in-soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefteram Pivoxil in 0.05 mol/L hydrochloric acid-methanol TS (1 in 100,000) as directed under Ultravio-let-visible Spectrophotometry <2.24>, and compare the spec-trum with the Reference Spectrum: both spectra exhibit simi-lar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cefteram Pivoxil as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefteram Pivoxil in deuterated chloroform for nuclear magnetic reso-nance spectroscopy (1 in 10) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using tetramethy-lsilane for nuclear magnetic resonance spectroscopy as an mL. Confirm that the peak area of cefteram pivoxil obtained with 10 mL of this solution is equivalent to 7 to 13z of that with 10 mL of the standard solution. System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of cefteram pivoxil are not less than 5000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of cefteram pivoxil is not more than 3.0z. Water <2.48> Not more than 3.0z (0.3 g, coulometric titration).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Cefteram Pivoxil according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 50 mg of Cefteram Pivoxil in 50 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 50 mL, and use this so-lution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the each area of the peaks, having the relative retention time of about 0.2 and about 0.9 to cefteram pivoxil, obtained from the sample so-lution is not larger than 1/2 times and 1.25 times the peak area of cefteram pivoxil from the standard solution, respec-tively, the area of the peak other than cefteram pivoxil and the peaks mentioned above is not larger than 1/4 times the peak area of cefteram pivoxil from the standard solution, and the total area of the peaks other than cefteram pivoxil is not larger than 2.75 times the peak area of cefteram pivoxil from the standard solution. For the area of the peak, having the relative retention time of about 0.1 to cefteram pivoxil, multiply the correction factor, 0.74. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 2 times as long as the retention time of cefteram pivoxil. System suitability— Test for required detectability: To exactly 1 mL of the standard solution add the mobile phase to make exactly 10 MS: Amount [mg (potency)] of Cefteram Pivoxil Mesity-lene Sulfonate RS taken Internal standard solution—A solution of methyl parahy-droxybenzoate in diluted acetonitrile (1 in 2) (1 in 1000). Operating c…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefteram Pivoxil and Cefteram Pivoxil Mesitylene Sulfonate RS, equivalent to about 40 mg (potency), dissolve each in 20 mL of diluted acetonitrile (1 in 2), add exactly 5 mL of the internal stand-ard solution and diluted acetonitrile (1 in 2) to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample so-lution and standard solution as directed under Liquid Chro-matography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of cefteram pivoxil to that of the internal standard. internal reference compound: it exhibits singlet signals A, B Amount [ mg (potency)] of cefteram (C H N O S ) and C, at around d 1.2 ppm, at around d 2.5 ppm and at around d 4.0 ppm, respectively. The ratio of the integrated ＝ MS × QT/QS × 1000 16 17 9 5 2 intensity of these signals, A:B:C, is about 3:1:1. D Optical rotation <2.49> [a]20: ＋35 – ＋439(0.4 g calculated on the anhydrous basis, methanol, 20 mL, 100 mm). Purity (1) Heavy metals <1.07>—Proceed with 1.0 g of Cefteram Pivoxil according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 50 mg of Cefteram Pivoxil in 50 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 50 mL, and use this so-lution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the each area of the peaks, having the relative retention time of about 0.2 and about 0.9 to cefteram pivoxil, obtained from the sample so-lution is not larger than 1/2 times and 1.25 times the peak area of cefteram pivoxil from the standard s…
storage conditions:
  en: Containers—Tight containers. Storage—In a cold place.
type: PharmacopoeiaMonograph

ceftibuten-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Ceftibuten Hydrate
  ja: セフチブテン水和物
monograph id: JP18-ceftibuten-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C15H14N4O6S2.2H2O
molecular weight: 446.46
cas number: 118081-34-8
definition:
  en: Ceftibuten Hydrate contains not less than 900 mg (potency) and not more than 1020 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Ceftibuten Hydrate occurs as a white to pale yellow-white crystalline powder. It is freely soluble in N,N-dimethylformamide and in dimethyl sulfoxide, and practically insoluble in water, in ethanol (95) and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Ceftibuten Hydrate in 0.1 mol/L phosphate buffer solution for antibiotics (pH 8.0) (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Ceftibuten Hydrate as directed in the paste method under the Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Ceftibut-en Hydrate in deuterated dimethyl sulfoxide for nuclear magnetic resonance spectroscopy (1 in 30), using tetra-methylsilane for nuclear magnetic resonance spectroscopy as an internal reference compound, as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>: it exhibits doublet signals A and B, at around d 3.2 ppm and at around d 5.1 ppm, a quartet signal C, at around d 5.8 ppm, and a singlet signal D, at around d 6.3 ppm. The ratio of integrated inten-sity of each signal except the signal at around d 3.2 ppm, B:C:D is about 1:1:1. D Optical rotation <2.49> [a]20: ＋135 – ＋1559(0.3 g calcu-lated on the anhydrous basis, 0.1 mol/L phosphate buffer solution for antibiotics, pH 8.0, 50 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Ceftibuten Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—(i) Keep the sample solution and the standard solution at not exceeding 59C and use within 2 hours after preparation. Dissolve 25 mg of Cefti-buten Hydrate in 20 mL of 0.1 mol/L phosphate buffer solu-tion for antibiotics (pH 8.0). To 4 mL of this solution add 0.1 mol/L phosphate buffer solution for antibiotics (pH 8.0) to make 20 mL, and use this solution as the sample solution. Pipet 5 mL of the sample solution, add 0.1 mol/L phosphate buffer solution for antibiotics (pH 8.0) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the area of the peak other than ceftibuten obtained from the sample solution is not larger than 1/5 times the peak area of ceftibuten from the standard solution, and the total area of the peaks other than ceftibuten from the sample solution is not larger than the peak area of ceftibuten from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 1.7 times as long as the retention time of ceftibuten, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 2 mL of the standard solution, and add 0.1 mol/L phosphate buffer solution for antibiotics (pH 8.0) to make exactly 20 mL. Confirm that the peak area of ceftibuten obtained with 5 mL of this solution is equivalent to 7 to 13z of that with 5 mL of the standard so-lution. System performance: Dissolve 5 mg of Ceftibuten Hydrate in 20 mL of…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Keep the sample solution and the standard solution at not exceeding 59C and use within 2 hours after prepara-tion. Weigh accurately an amount of Ceftibuten Hydrate and Ceftibuten Hydrochloride RS, equivalent to about 10 mg (potency), dissolve each in about 36 mL of 0.1 mol/L phosphate buffer solution for antibiotics (pH 8.0), add ex-actly 4 mL each of the internal standard solution, shake, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and calculate the ratios, QT and QS, of the peak area of ceftibuten to that of the internal standard. JP XVIII Official Monographs / Ceftizoxime Sodium 709 Amount [mg (potency)] of ceftibuten (C15H14N4O6S2) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Ceftibuten Hydrochloride RS taken Internal standard solution—A solution of methyl parahy-droxybenzoate in acetonitrile (3 in 4000). Operating conditions— ‌Detector: An ultraviolet absorption photometer (wave-length: 263 nm). Column: A stainless steel column 4 mm in inside diameter and 20 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (7 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of 0.005 mol/L n-decyl trimethy-lammonium bromide TS and acetonitrile (4:1). Flow rate: Adjust so that the retention time of ceftibuten is about 10 minutes. System suitability— System performance: Dissolve 5 mg of Ceftibuten Hydrate in 20 mL of 0.1 mol/L hydrochloric acid TS, and allow to stand at 409C for 1 hour. To 4 mL of this solution add 0.1 mol/L phosphate buffer solution for antibiotics (pH 8.0) to make 25 mL. When the procedure is run with 5 mL of this so-lution under the above operating conditions, trans-isomer of ceftibuten and ceftibuten are eluted in this order with the resolution between these pe…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant, and not exceeding 59C.
type: PharmacopoeiaMonograph

cefuroxime-axetil
type: ChemicalDrugMonograph
pref label:
  en: Cefuroxime Axetil
  ja: セフロキシム アキセチル
monograph id: JP18-cefuroxime-axetil
publisher: JP
status: Official
version: 18
molecular formula: C20H22N4O10S
molecular weight: 510.47
cas number: 64544-07-6
definition:
  en: Cefuroxime Axetil contains not less than 800 mg (potency) and not more than 850 mg (potency) per mg, calculated on the anhydrous and acetone-free basis.
appearance:
  en: Cefuroxime Axetil occurs as white to yellow-white non-crystalline powder. It is freely soluble in dimethylsulfoxide, soluble in metha-nol, sparingly soluble in ethanol (95), and very slightly solu-ble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cefuroxime Axetil in methanol (3 in 200,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cefuroxime Axetil RS pre-pared in the same manner as the sample solution: both spec-tra exhibit similar intensities of absorption at the same wave-lengths. Determine the infrared absorption spectrum of Cefuroxime Axetil as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Cefuroxime Axetil RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Determine the 1H spectrum of a solution of Cefuroxime Axetil in deuterated dimethylsulfoxide for nuclear magnetic resonance spectroscopy (1 in 20) as directed under Nuclear Magnetic Resonance Spectroscopy <2.21>, using tetramethylsilane for nuclear magnetic resonance spec-troscopy as an internal reference compound: it exhibits a doublet signal or a pair of doublet signals A at around d 1.5 ppm, a pair of singlet signals B at around d 2.1 ppm, and a singlet signal C at around d 3.9 ppm. The ratio of the inte-grated intensity of each signal, A:B:C, is about 1:1:1. D Optical rotation <2.49> [a]20: ＋41 – ＋479(0.5 g, metha-nol, 50 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cefuroxime Axetil according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 25 mg of Cefuroxime Axetil in 4 mL of methanol, add a solution of ammonium dihydrogenphosphate (23 in 1000) to make 10 mL, and use this solution as the sample solution. Pipet 1 mL of the sam-ple solution, add 40 mL of methanol and a solution of am-monium dihydrogenphosphate (23 in 1000) to make exactly JP XVIII Official Monographs / Cefuroxime Axetil 713 100 mL, and use this solution as the standard solution. Per-form the test with exactly 2 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and de-termine each peak area by the automatic integration method: the area of the peak other than cefuroxime axetil obtained from the sample solution is not larger than 1.5 times the total area of the two peaks of cefuroxime axetil from the standard solution, and the total area of the peaks other than cefuroxime axetil from the sample solution is not larger than 4 times the total area of the two peaks of cefuroxime axetil from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 3 times as long as the retention time of the peak having the larger retention time of the two peaks of cefuroxime axetil, beginning after the sol-vent peak. System suitability— Test for required detectability: Pipet 1 mL of the standard solution, and add 4 mL of methanol and a solution of am-monium dihydrogenphosphate (23 in 1000) to make exactly 10 mL. Confirm that the total area of the two peaks of cefuroxime axetil obtained with 2 mL of this solution is equivalent to 7 to 13z of that with 2 mL of the standard so-lution. System performance:…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Cefuroxime Axetil and Cefuroxime Axetil RS, equivalent to about 50 mg (po-tency), and dissolve each in methanol to make exactly 50 mL. Pipet 10 mL each of these solutions, add exactly 5 mL of the internal standard solution, 5 mL of methanol and a solution of ammonium dihydrogen phosphate (23 in 1000) to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the sum area of the two peaks of cefuroxime axetil to the peak area of the internal standard. the internal standard: the amount of acetone is not more Amount [ mg (potency)] of cefuroxime (C H N O S) than 1.3z. ＝ MS × QT/QS × 1000 16 16 4 8 Amount (z) of acetone ＝ MS/MT × QT/QS × 1/5 MS: Amount (g) of acetone taken MT: Amount (g) of Cefuroxime Axetil taken Internal standard solution—A solution of 1-propanol in dimethylsulfoxide (1 in 200). Operating conditions— Detector: A hydrogen flame-ionization detector. Column: A glass column 3 mm in inside diameter and 2 m in length, packed with siliceous earth for gas chromatogra-phy coated with a mixture of polyethylene glycol 600 for gas chromatography and polyethylene glycol 1500 for gas chro-matography (1:1) in the ratio of 20z (125 – 150 mm in parti-cle diameter). Column temperature: A constant temperature of about 909C. MS: Amount [mg (potency)] of Cefuroxime Axetil RS taken Internal standard solution—A solution of acetanilide in methanol (27 in 5000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 278 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 20 cm in length, packed with trimethylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of a solution…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

celecoxib
type: ChemicalDrugMonograph
pref label:
  en: Celecoxib
  ja: セレコキシブ
monograph id: JP18-celecoxib
publisher: JP
status: Official
version: 18
molecular formula: C17H14F3N3O2S
molecular weight: 381.37
cas number: 169590-42-5
definition:
  en: Celecoxib contains not less than 98.
appearance:
  en: Celecoxib occurs as a white, powder or crystal-line powder. It is freely soluble in methanol, soluble in ethanol (99.5), and practically insoluble in water. Melting point: 161 – 1649C Celecoxib shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Celecoxib in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and Pipet 1 mL of this solution, add a mixture of methanol and water (3:1) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 25 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area, AT, in the sample solution and the peak area of celecoxib, AS, in the standard solution by the automatic integration method, and calculate the amount of the related substances by the follow-ing equation: the amount of related substance A having the relative retention time of about 0.94 to celecoxib is not more than 0.4z, and each amount of the related substances other than related substance A is not more than 0.10z. Further-more, the total amount of the related substances is not more than 0.5z. Amount (z) of related substance ＝ MS/MT × AT/AS MS: Amount (mg) of Celecoxib RS taken MT: Amount (mg) of Celecoxib taken Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 1.5 times as long as the retention time of celecoxib, beginning after the solvent peak. System suitability— System performance and system repeatability: Proceed as directed in the system suitability in the Assay. Test for required detectability: Pipet 5 mL of the standard solution, and add a mixture of methanol and water (3:1) to make exactly 100 mL. Confirm that the peak area of celecox-ib obtained with 25 mL of this solution is equivalent to 3.5 to 6.5z of that with 25 mL of the standard solution. Water <2.48> Not more than 0.5z (0.3 g, volumetric titra-tion, direct titration). Residue on ignition <2.44> Not more than 0.2z (1.0 g, platinum crucible).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Celecoxib according to Method 4, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 20 ppm). (2) Related substances—Use the sample solution ob-tained in the Assay as the sample solution. Separately, weigh accurately about 50 mg of Celecoxib RS, dissolve in a mix-ture of methanol and water (3:1) to make exactly 100 mL. MS: Amount (mg) of Celecoxib RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 215 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with phenylated silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 609C. Mobile phase: Adjust 0.02 mol/L potassium dihydrogen phosphate TS to pH 3.0 with phosphoric acid. To 600 mL of this solution add 300 mL of methanol for liquid chromatog-raphy and 100 mL of acetonitrile for liquid chromatography. Flow rate: Adjust so that the retention time of celecoxib is about 22 minutes. ‌JP XVIII Official Monographs / Cellacefate 715 System suitability— System performance: When the procedure is run with 25 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of celecoxib are not less than 6000 and not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 25 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of celecoxib is not more than 1.0z.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 50 mg each of Celecoxib and Celecoxib RS, and dissolve each in a mixture of metha-nol and water (3:1) to make exactly 100 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 25 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine the peak areas, AT and AS, of celecoxib in each solution. compare the spectrum with the Reference Spectrum or the spectrum of a solution of Celecoxib RS prepared in the same manner as the sample solution: both spectra exhibit similar Amount (mg) of celecoxib (C ＝ MS × AT/AS 17H14F3N3O2S) intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Celecoxib, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Celecoxib RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. Purity (1) Heavy metals <1.07>—Proceed with 1.0 g of Celecoxib according to Method 4, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 20 ppm). (2) Related substances—Use the sample solution ob-tained in the Assay as the sample solution. Separately, weigh accurately about 50 mg of Celecoxib RS, dissolve in a mix-ture of methanol and water (3:1) to make exactly 100 mL. MS: Amount (mg) of Celecoxib RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 215 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with phenylated silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 609C. Mobile phase: Adjust 0.02 mol/L potassium dihydrogen phosphate TS to pH 3.0 with phosphoric acid. To 600 mL of this solution add 3…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

cellulose-acetate-phthalate
type: ChemicalDrugMonograph
pref label:
  en: Cellulose Acetate Phthalate
  ja: セラセフェート
monograph id: JP18-cellulose-acetate-phthalate
publisher: JP
status: Official
version: 18
cas number: 9004-38-0
appearance:
  en: Cellacefate occurs as a white, powder or grain. It is freely soluble in acetone, and practically insoluble in water and in ethanol (99.5).◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Cellacefate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cellacefate for Identification RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Viscosity <2.53> Weigh accurately a quantity of Cellace-fate, equivalent to 15 g calculated on the anhydrous basis, dissolve in 85 g of a mixture of acetone and water (249: 1 in mass), and use this solution as the sample solution. Perform the test with the sample solution at 25 ± 0.29C as directed in Method 1 to obtain the kinematic viscosity n. Separately, de-termine the density, r, of the sample solution as directed under Determination of Specific Gravity and Density <2.56>, and calculate the viscosity of the sample solution, h, as h ＝ rn: not less than 45 mPa･s and not more than 90 mPa･s.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) ◆Heavy metals <1.07>—Proceed with 2.0 g of Cellacefate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm).◆ (2) Free acids—Weigh accurately about 3 g of Cellace-fate, put in a glass-stoppered conical flask, add 100 mL of diluted methanol (1 in 2), stopper tightly, and filter after shaking for 2 hours. Wash both the flask and residue with two 10-mL portions each of diluted methanol (1 in 2), com-bine the washes to the filtrate, and titrate <2.50> with 0.1 mol/L sodium hydroxide VS (indicator: 2-3 drops of phenol-phthalein TS). Perform the blank determination with 120 mL of diluted methanol (1 in 2), and make any necessary correction. Amount (z) of free acids ＝ 0.8306A/M A: Amount (mL) of 0.1 mol/L sodium hydroxide VS con-sumed M: Amount (g) of Cellacefate taken, calculated on the an-hydrous basis The amount of free acids is not more than 3.0z, calcu-lated as phthalic acid (C8H6O4: 166.13). Water <2.48> Not more than 5.0z (0.5 g, volumetric titra-tion, direct titration, using a mixture of ethanol (99.5) and dichloromethane (3:2) instead of methanol for water deter-mination). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Carboxybenzoyl group—Weigh accurately about 1 g of Cellacefate, dissolve in 50 mL of a mixture of ethanol (95) and acetone (3:2), and titrate <2.50> with 0.1 mol/L so- dium hydroxide VS (indicator: 2 – 3 drops of phenolphthal-ein TS). Perform a blank determination in the same manner, and make any necessary correction. Content (z) of carboxybenzoyl group (C8H5O3) 1.491 × A－(1.795 × B) M ＝ 100 － B ×100 A: Amount (mL) of 0.1 mol/L sodium hydroxide VS con-sumed B: Amount (z) of free acids obtained in the Purity (2) M: Amount (g) of Cellacefate taken, calculated on the an-hydrous basis (2) Acetyl group—Weigh accurately about 0.1 g of Cel-lacefate, put in a glass-stoppered conical flask, add exactly 25 mL of 0.1 mol/L sodium hydroxide VS, and boil for 30 minutes under a reflux condenser. After cooling, add 2 – 3 drops of phenolphthalein TS, and titrate <2.50> the excess of sodium hydroxide with 0.1 mol/L hydrochloric acid VS. Perform a blank determination in the same manner. Content (z) of free acids and bound acetyl group (C2H3O) ＝ 0.4305A/M A: Amount (mL) of 0.1 mol/L sodium hydroxide VS con-sumed, corrected by the blank determination M: Amount (g) of Cellacefate taken, calculated on the an-hydrous basis ‌716 Content (z) of acetyl group (C2H3O) ＝100 × (P － 0.5182B)/(100 － B) － 0.5772C B: Amount (z) of free acids obtained in the Purity (2) C: Content (z) of carboxybenzoyl group P: Content (z) of free acids and bound acetyl group (C2H3O) ◆Containers and storage Containers—Tight containers.◆ Microcrystalline Cellulose
type: PharmacopoeiaMonograph

celmoleukin-genetical-recombination
type: ChemicalDrugMonograph
pref label:
  en: Celmoleukin (Genetical Recombination)
  ja: セルモロイキン（遺伝子組換え）
monograph id: JP18-celmoleukin-genetical-recombination
publisher: JP
status: Official
version: 18
molecular formula: S7
molecular weight: 15415.82
cas number: 94218-72-1
definition:
  en: Celmoleukin (Genetical Recombination) is a recom-binant human interleukin-2, and is a protein consisting of 133 amino acid residues. It is a solution. It contains not less than 0.
appearance:
  en: Celmoleukin (Genetical Recombination) oc-curs as a clear and colorless liquid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Add 100 mL of protein digestive enzyme TS to 100 mL of Celmoleukin (Genetical Recombination), shake, leave standing at 379C for 18 to 24 hours, and then add 2 mL of 2-mercaptoethanol. Leave at 379C for a further 30 minutes, and add 5 mL of trifluoroacetic acid solution (1 in 10). Use this solution as the sample solution. Separately, process with celmoleukin for liquid chromatography by using the same method. Use this solution as the standard so-lution. Perform the test with 50 mL each of the sample solu-tion and standard solution as directed under Liquid Chroma-tography <2.01> according to the following conditions, and compare the chromatograms obtained from the sample solu-tion and standard solution: the similar peaks are observed at the same retention time. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 215 nm). Column: A stainless steel column 4 mm in inside diameter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (particle size: 5 mm). Column temperature: A constant temperature of about 259C. Mobile phase A: A solution of trifluoroacetic acid (1 in 1000). Mobile phase B: A solution of trifluoroacetic acid in a mixture of acetonitrile and water (17:3) (1 in 1000). Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. and phenol (100:10:1). Replace the vial interior with inert gas or reduce the pressure, and heat at about 1159C for 24 hours. After drying under vacuum, dissolve in 0.5 mL of 0.02 mol/L hydrochloric acid TS, and use this solution as 0 – 5 5 – 45 100 → 60 0 → 40 45 – 75 60 → 0 40 → 100 75 – 85 Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) the sample solution (1). To the other hydrolysis tube, add 100 mL of ice cold performic acid, oxidize for 1.5 hours on ice, add 50 mL of hydrobromic acid, and dry under vacuum. Add 200 mL of water, repeat the dry under vacuum proce-dure two…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: ◆(1) Heavy metals <1.07>—Proceed with 2.0 g of Powdered Cellulose according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm).◆ Water-soluble substances—Shake 6.0 g of Powdered Cellulose with 90 mL of recently boiled and cooled water, and allow to stand for 10 minutes with occasional shaking. Filter, with the aid of vacuum through a filter paper, discard the first 10 mL of the filtrate, and pass the subsequent fil-trate through the same filter, if necessary, to obtain a clear filtrate. Evaporate a 15.0-mL portion of the filtrate in a tared evaporating dish to dryness without charring, dry at 1059C for 1 hour, and weigh after allowing to cool in a desiccator: the difference between the mass of the residue and the mass obtained from a blank determination does not exceed 15.0 mg (1.5z). Diethyl ether-soluble substances—Place 10.0 g of Powdered Cellulose in a column having an internal diameter of about 20 mm, and pass 50 mL of peroxide-free diethyl [94218-72-1] Celmoleukin (Genetical Recombination) is a recom-binant human interleukin-2, and is a protein consisting of 133 amino acid residues. It is a solution. It contains not less than 0.5 and not more than 1.5 mg of protein per mL, and 1 mg of this protein con-tains potency not less than 8.0 × 106 units. Description Celmoleukin (Genetical Recombination) oc-curs as a clear and colorless liquid. Identification (1) Add 100 mL of protein digestive enzyme TS to 100 mL of Celmoleukin (Genetical Recombination), shake, leave standing at 379C for 18 to 24 hours, and then add 2 mL of 2-mercaptoethanol. Leave at 379C for a further 30 minutes, and add 5 mL of trifluoroacetic acid solution (1 in 10). Use this solution as the sample solution. Separately, process with celmoleukin for liquid chromatography by using the same method. Use this solution as the standard so-lution. Perform the test with 50 mL each of the sample solu-tion and standard solution as direc…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Total protein content—Measure accurately 1 mL of Celmoleukin (Genetical Recombination) and add water to make exactly 10 mL. Use this solution as the sample solution. Separately, weigh accurately about 50 mg of bovine serum albumin for assay in water to prepare standard dilu-tion solutions of 50, 100, and 150 mg/mL. Measure exactly 1 mL of the sample solution and each standard dilution solu-tion, add exactly 2.5 mL of alkaline copper TS for protein content determination, shake, and leave for 15 minutes. Next, add exactly 2.5 mL of water and 0.5 mL of dilute Folin's TS, and leave at 379C for 30 minutes. Measure the absorbances of these solutions at 750 nm as directed under Ultraviolet-visible Spectrophotometry <2.24>, using 1 mL of water processed in the same way as control. Using the calibration curve prepared from the absorbance of the stand-ard dilution solution, calculate the protein content of Cel- moleukin (Genetical Recombination). (2) Specific activity—Measure exactly 0.1 mL of Cel-moleukin (Genetical Recombination) and add exactly 0.9 mL of culture medium for celmoleukin to make the sample solution. Separately, take one Interleukin-2 RS and add exactly 1 mL of water to dissolve. This is the standard solu-tion. Dilute exactly the sample and standard solutions in serially two-fold steps with culture medium for celmoleukin, and add equal volumes of interleukin-2 dependent mouse natural killer NKC3 cells to the serially diluted solutions. The control solution is a mixture of equal volumes of inter-leukin-2 dependent mouse natural killer NKC3 and culture medium for celmoleukin. Incubate these solutions at 379C for 16 to 24 hours. Following this, add a volume of 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl-2H-tetrazolium bromide TS that is 1/5 that of the volume of culture medium for cel-moleukin, incubate at 379C for 4 to 6 hours, add a volume of sodium lauryl sulfate TS equivalent to the volume of the culture medium for celmoleukin, and leave for 24 to 48 hours…
storage conditions:
  en: Containers—Tight containers. Storage—At －209C or lower.
type: PharmacopoeiaMonograph

cera-alba
type: ChemicalDrugMonograph
pref label:
  en: Cera Alba
  ja: サラシミツロウ
monograph id: JP18-cera-alba
publisher: JP
status: Official
version: 18
appearance:
  en: White Beeswax occurs as white to yellowish white masses. It has a characteristic odor. It is comparatively brittle when cooled, and the fractured surface is granular, and non-crystalline. It is slightly soluble in diethyl ether, and practically insolu-ble in water and in ethanol (99.5). Acid value <1.13> 5 – 9 or 17 – 22 Weigh accurately about 6 g of White Beeswax, place in a glass-stoppered 250-mL flask, and add 50 mL of ethanol (99.5). Warm the mixture to dissolve the wax, add 1 mL of phenolphthalein TS, and proceed as directed in the Acid value. Perform a blank deter-mination using solvent which is not previously neutralized, and make any necessary correction. Saponification value <1.13> 80 – 100 Weigh accurately about 3 g of White Beeswax, place in a glass-stoppered 250-mL flask, and add exactly 25 mL of 0.5 mol/L potas-sium hydroxide-ethanol VS and 50 mL of ethanol (95), heat under a reflux condenser for 4 hours, and proceed as di-rected in the Saponification value.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Paraffin, fat, Japan wax or resin—Melt White Beeswax at the lowest possible temperature, drip the liquid into a vessel containing ethanol (95) to form granules, and allow them to stand in air for 24 hours. Drop the granules into two mixtures of ethanol (95) and water, one adjusted so as to have a specific gravity of 0.95 and the other 0.97: the granules sink or are suspended in the mixture with the spe-cific gravity of 0.95, and float or are suspended in the other mixture.
storage conditions:
  en: Containers—Well-closed contain-ers.

cera-carnauba
type: ChemicalDrugMonograph
pref label:
  en: Cera Carnauba
  ja: カルナウバロウ
monograph id: JP18-cera-carnauba
publisher: JP
status: Official
version: 18
appearance:
  en: Carnauba Wax occurs as light yellow to light brown, hard and brittle masses or white to light yellow pow-der. It has a slight, characteristic odor. It is tasteless. It is practically insoluble in water, in ethanol (95), in diethyl ether and in xylene. Specific gravity d 20: 0.990 – 1.002 Melting point: 80 – 869C Acid value <1.13> Not more than 10.0. Use a mixture of xylene and ethanol (95) (2:1) as solvent. Saponification value <1.13> 78 – 95 Weigh accurately about 3 g of Carnauba Wax in a 300-mL flask, add 25 mL of xylene, and dissolve by warming. To this solution add 50 mL of ethanol (95) and exactly 25 mL of 0.5 mol/L potassium hydroxide-ethanol VS, and proceed as directed in the Saponification value. The time of heating should be 2 hours ‌1976‌‌ Cassia Seed / Crude Drugs and Related Drugs and the titration should be done by warming. Iodine value <1.13> 5 – 14 (Dissolve the sample by shaking a glass-stoppered flask in warm water.) ‌Containers and storage Containers—Well-closed contain-ers. Cassia Seed Cassiae Semen

cera-flava
type: ChemicalDrugMonograph
pref label:
  en: Cera Flava
  ja: ミツロウ
monograph id: JP18-cera-flava
publisher: JP
status: Official
version: 18
appearance:
  en: Yellow Beeswax occurs as light yellow to brownish yellow masses. It has a characteristic odor, which is not rancid. It is comparatively brittle when cooled, and the fractured surface is granular, and non-crystalline. Acid value <1.13> 5 – 9 or 17 – 22 Weigh accurately about 6 g of Yellow Beeswax, place in a glass-stoppered 250-mL flask, and add 50 mL of ethanol (99.5). Warm the mixture to dissolve the wax, add 1 mL of phenolphthalein TS, and proceed as directed in the Acid value. Perform a blank deter-mination using solvent which is not previously neutralized, and make any necessary correction. ‌JP XVIII Crude Drugs and Related Drugs / Belladonna Root 1957 Saponification value <1.13> 80 – 100 Weigh accurately about 3 g of Yellow Beeswax, place in a 250-mL glass-stoppered flask, and add 25 mL of 0.5 mol/L potassium hy-droxide-ethanol and 50 mL of ethanol (95), heat under a reflux condenser for 4 hours, and proceed as directed in the Saponification value.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Paraffin, fat, Japan wax or resin—Melt Yellow Beeswax at the lowest possible temperature, drip the liquid into a glass vessel containing ethanol (95) to form granules, and allow them to stand in air for 24 hours. Drop the gran-ules into two mixtures of ethanol (95) and water, one adjusted so as to have a specific gravity of 0.95 and the other 0.97: the granules sink or are suspended in the mixture with the specific gravity of 0.95, and float or are suspended in the other mixture.
storage conditions:
  en: Containers—Well-closed contain-ers.

cetanol
type: ChemicalDrugMonograph
pref label:
  en: Cetanol
  ja: セタノール
monograph id: JP18-cetanol
publisher: JP
status: Official
version: 18
appearance:
  en: Cetanol occurs as unctuous, white, flakes, granules, or masses. It has a faint, characteristic odor. It is tasteless. It is very soluble in pyridine, freely soluble in ethanol (95), in ethanol (99.5) and in diethyl ether, very slightly soluble in acetic anhydride, and practically insoluble in water.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity of solution—Dissolve 3.0 g of Cetanol in 25 mL of ethanol (99.5) by warming: the solution is clear. (2) Alkalinity—To the solution obtained in (1) add 2 drops of phenolphthalein TS: no red color develops. Residue on ignition <2.44> Not more than 0.05z (2 g).
storage conditions:
  en: Containers—Well-closed contain-ers.

cetirizine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cetirizine Hydrochloride
  ja: セチリジン塩酸塩
monograph id: JP18-cetirizine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C21H25ClN2O3.2HCl
molecular weight: 461.81
cas number: 83881-52-1
definition:
  en: Cetirizine Hydrochloride, when dried, contains not less than 99.
appearance:
  en: Cetirizine Hydrochloride occurs as a white crystalline powder. It is very soluble in water, and slightly soluble in ethanol (99.5). It dissolves in 0.1 mol/L hydrochloric acid TS. A solution of Cetirizine Hydrochloride (1 in 10) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cetirizine Hydrochloride in 0.1 mol/L hydro-chloric acid TS (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cetirizine Hydrochloride as directed in the potassium chlo-ride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Cetirizine Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cetirizine Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 0.10 g of Cetirizine Hy-drochloride in 50 mL of the mobile phase, and use this solu-tion as the sample solution. Pipet 2 mL of the sample solu-tion, add the mobile phase to make exactly 50 mL. Pipet 5 mL of this solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Per-form the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and de-termine each peak area of each solution by the automatic in-tegration method: the area of each peak other than cetirizine obtained from the sample solution is not larger than the peak area of cetirizine from the standard solution. And the total area of the peaks other than cetirizine from the sample solu-tion is not larger than 2.5 times the peak area of cetirizine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 230 nm). Column: A stainless steel column 4.0 mm in inside diame-ter and 25 cm in length, packed with silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of acetonitrile and diluted 0.5 mol/L sulfuric acid TS (2 in 25) (47:3). Flow rate: Adjust so that the retention time of cetirizine is about 9 minutes. Time span of measurement: About 3 times as long as the retention time of cetirizine, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 5 mL of the standard solution, and add the mobile phase to make exactly 10 mL. Confirm that the peak area of cetirizine obtained with 10 mL of this solution is equivalent to 35 to 65z of that with 10 mL of…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of Cetirizine Hydro-chloride, previously dried, dissolve in 70 mL of a mixture of acetone and water (7:3), and titrate <2.50> to the second equivalence point with 0.1 mol/L sodium hydroxide VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 15.39 mg of C21H25ClN2O3.2HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

cetotiamine-hydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Cetotiamine Hydrochloride Hydrate
  ja: セトチアミン塩酸塩水和物
monograph id: JP18-cetotiamine-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C18H26N4O6S.HCl.H2O
molecular weight: 480.96
definition:
  en: Cetotiamine Hydrochloride Hydrate contains not less than 98.
appearance:
  en: Cetotiamine Hydrochloride Hydrate occurs as white, crystals or crystalline powder. It is odorless or has a faint characteristic odor. It is freely soluble in water and in ethanol (99.5). It dissolves in 0.01 mol/L hydrochloric acid TS. Melting point: about 1329C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cetotiamine Hydrochloride Hydrate in 0.01 mol/L hydrochloric acid TS (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cetotiamine Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cetotiamine Hydrochloride Hydrate as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cetotiamine Hydrochloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Cetotiamine Hydrochloride Hydrate (1 in 50) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution ob-tained by dissolving 1.0 g of Cetotiamine Hydrochloride Hy-drate in 10 mL of water is clear and has no more color than the following control solution. Control solution: Mix exactly 1.5 mL of Cobalt (II) Chlo-ride CS, exactly 36 mL of Iron (III) Chloride CS and exactly 12.5 mL of diluted dilute hydrochloric acid (1 in 10). Pipet 1 mL of this mixture, and add diluted dilute hydrochloric acid (1 in 10) to make exactly 100 mL. Heavy metals <1.07>—Proceed with 1.0 g of Cetotia- mine Hydrochloride Hydrate according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 50 mg of Cetotiamine Hydrochloride Hydrate in 50 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the area of the peak other than cetotiamine obtained from the sample solution is not larger than the peak area of cetotia-mine from the standard solution, and the total area of the peaks other than cetotiamine from the sample solution is not larger than 2 times the peak area of cetotiamine from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 3 times as long as the retention time of cetotiamine, beginning after the solvent peak. System suitability— Test for required detectability: To exactly 2 mL of the standard solution add the mobile phase to make exactly 20 mL. Confirm that the peak area of cetotiamine obtained with 10 mL of this …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 30 mg each of Cetotiamine Hydrochloride Hydrate and Cetotiamine Hydrochloride RS (separately determine the water <2.48> in the same manner as Cetotiamine Hydrochloride Hydrate), add exactly 10 mL each of the internal standard solution, then add a mixture of water and methanol (1:1) to make 50 mL. To 2 mL each of these solutions add a mixture of water and methanol (1:1) to make 10 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of cetotiamine to that of the internal standard. Amount (mg) of cetotiamine hydrochloride (C18H26N4O6S.HCl) ＝ MS × QT/QS MS: Amount (mg) of Cetotiamine Hydrochloride RS taken, calculated on the anhydrous basis Internal standard solution—A solution of propyl parahy-droxybenzoate in a mixture of water and methanol (1:1) (1 in 800). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 245 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). ‌726 Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 1.0 g of sodium 1-heptanesul-fonate in diluted acetic acid (100) (1 in 100) to make 1000 mL. To 1 volume of this solution add 1 volume of methanol. Flow rate: Adjust so that the retention time of cetotiamine is about 10 minutes. System suitability— System performance: When the procedure is run with 5 mL of the standard solution under the above operating condi-tions, cetotiamine and the internal standard are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeated 6 times with 5 mL of the standard solution under the a…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cetraxate-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cetraxate Hydrochloride
  ja: セトラキサート塩酸塩
monograph id: JP18-cetraxate-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C17H23NO4.HCl
molecular weight: 341.83
cas number: 27724-96-5
appearance:
  en: Cetraxate Hydrochloride occurs as white, crys-tals or crystalline powder. It is soluble in methanol, sparingly soluble in water and in ethanol (95), and practically insoluble in diethyl ether. Melting point: about 2369C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cetraxate Hydrochloride in methanol (1 in 2500) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wavelengths. Dissolve 0.5 g of Cetraxate Hydrochloride in 5 mL of a mixture of water and 2-propanol (1:1) by warming, cool to below 259C. Filter, dry the formed crystals in vacuum for 4 hours, and further dry at 1059C for 1 hour. Determine the infrared absorption spectrum of the dried matter as directed in the potassium chloride disk method under Infrared Spec-trophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Cetraxate Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cetraxate Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Cetraxate Hydrochloride according to Method 3, and per-form the test with a solution of magnesium nitrate hexahy-drate in ethanol (95) (1 in 5) (not more than 2 ppm). cis Isomer—Dissolve 0.10 g of Cetraxate Hydrochlo-ride in 10 mL of water, and use this solution as the sample solution. To exactly 5 mL of the sample solution add water to make exactly 100 mL. To exactly 2 mL of this solution add water to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area of both solu-tions by the automatic integration method: the area of the peak, having the relative retention time 1.3 to 1.6 to cetraxate from the sample solution is not larger than the peak area of cetraxate from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 220 nm). Column: A stainless steel column 6 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Adjust the pH of a mixture of water, meth-anol and 0.5 mol/L ammonium acetate TS (15:10:4) to 6.0 with acetic acid (31). Flow rate: Adjust so that the retention time of cetraxate is about 10 minutes. System suitability— System performance: Dissolve 0.02 g of Cetraxate Hydro-chloride and 0.01 g of phenol in 100 mL of water. To 2 mL of this solution add water to make 20 mL. When the proce-dure is run with 10 mL of this solution under the above oper-ating conditions, cetraxate and phenol a…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Cetraxate Hydro-chloride, previously dried, dissolve in 100 mL of water, and adjust the pH of this solution to between 7.0 and 7.5 with dilute sodium hydroxide TS. To this solution add 10 mL of formaldehyde solution, stir for about 5 minutes, and titrate <2.50> with 0.1 mol/L sodium hydroxide VS by taking over about 20 minutes (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 34.18 mg of C17H23NO4.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

chenodeoxycholic-acid
type: ChemicalDrugMonograph
pref label:
  en: Chenodeoxycholic Acid
  ja: ケノデオキシコール酸
monograph id: JP18-chenodeoxycholic-acid
publisher: JP
status: Official
version: 18
molecular formula: C24H40O4
molecular weight: 392.57
definition:
  en: Chenodeoxycholic Acid, when dried, contains not less than 98.
appearance:
  en: Chenodeoxycholic Acid occurs as white, crys- (2), and the spot corresponding to the spot from the stand- ‌728‌ ard solution (3) is not more intense than the spot from the standard solution (3). As compared to the spots with the standard solutions A, B, C, D and E, the spots other than the principal spot and the spots mentioned above from the sample solution are not more intense than the spot from the standard solution E, and the total amount of them is not more than 1.5z. Loss on drying <2.41> Not more than 1.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Chenodeoxycholic Acid, previously dried, as directed in the potassium bromide disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋11.0 – ＋13.09(after dry-ing, 0.4 g, ethanol (99.5), 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 0.36 g of Chenodeoxycholic Acid in 30 mL of methanol, add 10 mL of dilute nitric acid and water to make 50 mL, and perform the test with this solution. Prepare the control solution as follows: To 1.0 mL of 0.01 mol/L hydrochloric acid VS add 30 mL of methanol, 10 mL of dilute nitric acid and water to make 50 mL (not more than 0.1z). Heavy metals <1.07>—Proceed with 1.0 g of Chenodeoxycholic Acid according to Method 4, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Barium—To 2.0 g of Chenodeoxycholic Acid add 100 mL of water, and boil for 2 minutes. To this solution add 2 mL of hydrochloric acid, boil for 2 minutes, filter after cooling, and wash the filter with water until to get 100 mL of the filtrate. To 10 mL of the filtrate add 1 mL of dilute sulfuric acid: no turbidity appears. Related substances—Dissolve 0.20 g of Chenodeoxy-cholic Acid in a mixture of acetone and water (9:1) to make exactly 10 mL, and use this solution as the sample solution. Separately, dissolve 10 mg of lithocholic acid for thin-layer chromatography in the mixture of acetone and water (9:1) to make exactly 10 mL. Pipet 2 mL of this solution, add the mixture of acetone and water (9:1) to make exactly 100 mL, and use this solution as the standard solution (1). Separately, dissolve 10 mg of ursodeoxycholic acid in the mixture of ace-tone and water (9:1) to make exactly 100 mL, and use this solution as the standard solution (2). Separately, dissolve 10 mg of cholic acid for thin-layer chromatography in the mix-ture of acetone and water (9:1) to make exactly 100 mL, and use this solution as the standard solution (3). Pipet 1 mL of the sample solution, and add the mixture of acetone and water (9:1) to make exactly 20 mL. Pipet 0.5 mL, 1 mL, 2 mL, 3 mL and 5 mL of this solution, add the mixture of ace-tone and water (9:1) to each of them to make exactly 50 mL, and designate these solutions as standard s…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Chenodeoxycholic Acid, previously dried, dissolve in 40 mL of ethanol (95) and 20 mL of water, and titrate <2.50> with 0.1 mol/L sodium hydroxide VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 39.26 mg of C24H40O4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

chloral-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Chloral Hydrate
  ja: 抱水クロラール
monograph id: JP18-chloral-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C2H3Cl3O2
molecular weight: 165.4
definition:
  en: Chloral Hydrate contains not less than 99.
appearance:
  en: Chloral Hydrate occurs as colorless crystals. It has a pungent odor and an acrid, slightly bitter taste. It is very soluble in water, and freely soluble in ethanol (95) and in diethyl ether. It slowly volatilizes in air.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.2 g of Chloral Hydrate in 2 mL of water, and add 2 mL of sodium hydroxide TS: the turbidity is produced, and it separates into two clear layers by warming. (2) Heat 0.2 g of Chloral Hydrate with 3 drops of aniline and 3 drops of sodium hydroxide TS: the disagreeable odor of phenylisocyanide (poisonous) is perceptible.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Chloral Hydrate in 2 mL of water: the solution is clear and colorless. Acidity—Dissolve 0.20 g of Chloral Hydrate in 2 mL of water, and add 1 drop of methyl orange TS: a yellow color develops. Chloride <1.03>—Perform the test with 1.0 g of Chlo- ral Hydrate. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.011z). Chloral alcoholate—Warm 1.0 g of Chloral Hydrate with 10 mL of sodium hydroxide TS, filter the upper layer, add iodine TS to the filtrate until a yellow color develops, and allow the solution to stand for 1 hour: no yellow precipi-tate is produced. Benzene—Warm the solution obtained in (1) with 3 mL of water: no odor of benzene is perceptible. Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 4 g of Chloral Hydrate in a glass-stoppered flask, add 10 mL of water and exactly 40 mL of 1 mol/L sodium hydroxide VS, and allow the mixture to stand for exactly 2 minutes. Titrate <2.50> the excess sodium hydroxide immediately with 0.5 mol/L sulfuric acid VS (in-dicator: 2 drops of phenolphthalein TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 1 mol/L sodium hydroxide VS ＝ 165.4 mg of C2H3Cl3O2
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

chloramphenicol-palmitate
type: ChemicalDrugMonograph
pref label:
  en: Chloramphenicol Palmitate
  ja: クロラムフェニコールパルミチン酸エステル
monograph id: JP18-chloramphenicol-palmitate
publisher: JP
status: Official
version: 18
molecular formula: C27H42Cl2N2O6
molecular weight: 561.54
cas number: 530-43-8
definition:
  en: Chloramphenicol Palmitate contains not less than 558 mg (potency) and not more than 587 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Chloramphenicol Palmitate occurs as a white to grayish white, crystalline powder. It is freely soluble in acetone, sparingly soluble in metha-nol and in ethanol (99.5), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Chloramphenicol Palmitate in ethanol (99.5) (1 in 33,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of a solution of Chloram-phenicol Palmitate RS prepared in the same manner as the exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. The test should be performed within 30 minutes after the sample solution and standard solution are prepared. Determine each peak area by the automatic integration method: the total area of the peaks other than the peak of chloramphenicol palmitate obtained from the sample solution is not larger than 3.5 times the peak area of chloramphenicol palmitate from the standard solution. For the peak areas for chloramphenicol, having the relative retention time of about 0.5 to chloramphenicol palmitate, and for chloramphenicol dipalmitate, having the relative retention time of about 5.0, multiply their correction factors, 0.5 and 1.4, respectively. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 270 nm). Column: A stainless steel column 6.0 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 209C. Mobile phase: Methanol. Flow rate: Adjust so that the retention time of chloram-phenicol palmitate is about 5 minutes. Time span of measurement: About 6 times as long as the retention time of chloramphenicol palmitate. System suitability— Test for required detectability: Dissolve 50 mg of Chlo-ramphenicol Palmitate in 50 mL of methanol. To 1 mL of this solution, add methanol to make 100 mL, and use this so-lution as the solution for system suitability test. Pipet 5 mL of the solution for system suitability test, and add methanol to make e…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Chloramphenicol Palmitate and Chloramphenicol Palmitate RS, equivalent to about 37 mg (potency), dissolve each in 40 mL of methanol and 1 mL of acetic acid (100), and add methanol to make ex-actly 50 mL. Pipet 10 mL each of these solutions, add the mobile phase to make exactly 25 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of chloramphenicol palmitate in each solution. Amount [ mg (potency)] of chloramphenicol (C11H12Cl2N2O5) ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Chloramphenicol Palmitate RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column 3.9 mm in inside diame-ter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of methanol, water and acetic acid (100) (172:27:1). Flow rate: Adjust so that the retention time of chloram-phenicol palmitate is about 7 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates of the peak of chlo-ramphenicol palmitate is not less than 2400. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of chloramphenicol palmitate is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

chloramphenicol
type: ChemicalDrugMonograph
pref label:
  en: Chloramphenicol
  ja: クロラムフェニコール
monograph id: JP18-chloramphenicol
publisher: JP
status: Official
version: 18
molecular formula: C11H12Cl2N2O5
molecular weight: 323.13
cas number: 56-75-7
definition:
  en: Chloramphenicol contains not less than 980 mg (po-tency) and not more than 1020 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Chloramphenicol occurs as white to yellow-white, crystals or crystalline powder. It is freely soluble in methanol and in ethanol (99.5), and slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of the sample solution obtained in the Assay as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Chloramphenicol RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Chloramphenicol as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Chloramphenicol RS: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋18.5 – ＋21.59 (1.25 g, ethanol (99.5), 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Chloramphenicol according to Method 2, and perform the test. Prepare the control solution with 2.5 mL of Standard Lead Solution (not more than 25 ppm). (2) Related substances—Dissolve 0.10 g of Chloram-phenicol in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 100 mL, and use this solution as the standard solution (1). Pipet 10 mL of the standard solu-tion (1), add methanol to make exactly 20 mL, and use this ‌JP XVIII Official Monographs / Chloramphenicol Palmitate 729 solution as the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 20 mL each of the sample solution and standard solutions (1) and (2) on a plate of silica gel with ‰uorescent indicator for thin-layer chromatography, develop the plate with a mixture of ethyl acetate, methanol and acetic acid (100) (10:1:1) to a distance of about 15 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot and the spot of the starting point obtained from the sample solution are not more intense than the spot from the standard solution (1), and the total amount of these spots from the sample so-lution is not more than 2.0z. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Chloramphenicol and Chloramphenicol RS, equivalent to about 50 mg (po-tency), dissolve each in 10 mL of methanol, and add water to make exactly 50 mL. Pipet 20 mL each of these solutions, and add water to make exactly 100 mL. Pipet 10 mL each of these solutions, add water to make exactly 100 mL, and use these solutions as the sample solution and standard solution. Determine the absorbances, AT and AS, of the sample solution and standard solution at 278 nm as directed under Ultraviolet-visible Spectrophotometry <2.24>. sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Dissolve 5 mg each of Chloramphenicol Palmitate and Chloramphenicol Palmitate RS in 1 mL of acetone, and use these solutions as the sample solution and standard solu-tion. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of acetone and cyclohexane (1:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the principal spot obtained from the sample solution has the same Rf value as the spot from the standard solution. D Optical rotation <2.49> [a]25: ＋21 – ＋259(1 g calculated on the dried basis, ethanol (99.5), 20 mL, 100 mm). Melting point <2.60> 91 – 969C Purity (1) Heavy metals <1.07>—Proceed with 1.0 g of Chloramphenicol Palmitate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Chloramphenicol Palmitate according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 50 mg of Chloram-phenicol Palmitate in 50 mL of methanol, and use this solu- Amount [mg (potency)] of chlorampheni…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

chlordiazepoxide
type: ChemicalDrugMonograph
pref label:
  en: Chlordiazepoxide
  ja: クロルジアゼポキシド
monograph id: JP18-chlordiazepoxide
publisher: JP
status: Official
version: 18
molecular formula: C16H14ClN3O
molecular weight: 299.75
cas number: 58-25-3
definition:
  en: Chlordiazepoxide, when dried, contains not less diazepoxide RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorp-tion at the same wavelengths.
appearance:
  en: Chlordiazepoxide occurs as white to light yel- low, crystals or crystalline powder. It is freely soluble in acetic acid (100), sparingly soluble in ethanol (95), very slightly soluble in diethyl ether, and practi-cally insoluble in water. It dissolves in dilute hydrochloric acid. It is gradually affected by light. Melting point: about 2409C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Chlordiazepoxide in 0.1 mol/L hydrochloric acid TS (1 in 200,000) as directed under Ultraviolet-visible Spec-trophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Chlor- Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 29.98 mg of C16H14ClN3O
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Chlordiazepoxide according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 0.20 g of Chlordiazepoxide in exactly 10 mL of a mixture of methanol and ammonia TS (97:3), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of methanol and ammonia TS (97:3) to make ex-actly 200 mL, and use this solution as the standard solution (1). Separately, dissolve 10 mg of 2-amino-5-chloroben-zophenone for thin-layer chromatography in methanol to make exactly 200 mL, and use this solution as the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 25 mL of the sample solution and 5 mL each of the standard solutions (1) and (2) on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate and ethanol (99.5) (19:1) to a distance of about 12 cm, and air-dry the plate. Examine under ultravio-let light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution (1). Spray evenly a solution of sodium nitrite in 1 mol/L hydrochloric acid TS (1 in 100) on the plate, allow to stand for 1 minute, and spray evenly N-(1-naphthyl)-N?-diethylethylenediamine oxalate-acetone TS on the plate: the spots from the sample solution are not more intense than the spots from the standard solution (2). Loss on drying <2.41> Not more than 0.5z (1 g, in vacu-um, phosphorus (V) oxide, 609C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Chlordiazepoxide, previously dried, and dissolve in 50 mL of acetic acid (100). Titrate <2.50> with 0.1 mol/L perchloric acid VS until the than 98.5z of chlordiazepoxide (C 16H14 ClN3O). color of the supernatant liquid changes from purple through blue-purple to blue (indicator: 3 drops of crystal violet TS). Description Chlordiazepoxide occurs as white to light yel- low, crystals or crystalline powder. It is freely soluble in acetic acid (100), sparingly soluble in ethanol (95), very slightly soluble in diethyl ether, and practi-cally insoluble in water. It dissolves in dilute hydrochloric acid. It is gradually affected by light. Melting point: about 2409C (with decomposition). Identification (1) Determine the absorption spectrum of a solution of Chlordiazepoxide in 0.1 mol/L hydrochloric acid TS (1 in 200,000) as directed under Ultraviolet-visible Spec-trophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Chlor- Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 29.98 mg of C16H14ClN3O
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

chlorhexidine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Chlorhexidine Hydrochloride
  ja: クロルヘキシジン塩酸塩
monograph id: JP18-chlorhexidine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C22H30Cl2N10.2HCl
molecular weight: 578.37
cas number: 3697-42-5
definition:
  en: Chlorhexidine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Chlorhexidine Hydrochloride occurs as a white crystalline powder. It is odorless, and has a bitter taste. It is soluble in formic acid, slightly soluble in methanol and in warm methanol, and practically insoluble in water, in ethanol (95) and in diethyl ether. It is gradually colored by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Chlorhexidine Hy-drochloride in 5 mL of methanol by warming, and add 1 mL of bromine TS and 1 mL of 8 mol/L sodium hydroxide TS: a deep red color is produced. Dissolve 0.3 g of Chlorhexidine Hydrochloride in 10 ‌736‌ mL of 6 mol/L hydrochloric acid TS, cool in ice, and add 10 mL of 8 mol/L sodium hydroxide TS dropwise with stirring: a white precipitate is produced. Collect the precipitate, wash with water, recrystallize from diluted ethanol (95) (7 in 10), and dry at 1059C for 30 minutes: the crystals so obtained melt <2.60> between 1309C and 1349C. Dissolve 0.1 g of Chlorhexidine Hydrochloride in 50 mL of dilute nitric acid: the solution responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Chlorhexidine Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—To 1.0 g of Chlorhexidine Hydro- chloride in a crucible add 10 mL of a solution of magnesium nitrate hexahydrate in ethanol (95) (1 in 10), fire the ethanol (95) to burn, and heat gradually to incinerate. If a car-bonized substance remains, moisten with a small amount of nitric acid, and ignite to incinerate. Cool, add 10 mL of dilute hydrochloric acid to the residue, dissolve by warming on a water bath, use this solution as the test solution, and perform the test (not more than 2 ppm). p-Chloroaniline—Dissolve 0.10 g of Chlorhexidine Hydrochloride in 2 mL of formic acid, and add 15 mL of 1 mol/L hydrochloric acid TS and 20 mL of water immedi-ately. Add 0.3 mL of sodium nitrite TS, shake, and allow to stand for 2 minutes. Add 4 mL of ammonium amidosulfate TS, and then allow to stand for 1 minute. Add 5 mL of N-(1-naphthyl)-N?-diethylethylenediamine oxalate-acetone TS, allow to stand for 10 minutes, and add 1 mL of ethanol (95) and water to make 50 mL: the solution has no more color than the following control solution. Control solution: Dissolve 20 mg of 4-chloroaniline in 10 mL of 1 mol/L hydrochloric acid TS, and add water to make exactly 100 mL. Pipet 5 mL of the solution, and add water to make exactly 100 mL. To 2.0 mL of the solution add 2 mL of formic acid, 15 mL of 1 mol/L hydrochloric acid TS and 20 mL of water, and proceed in the same manner. Loss on drying <2.41> Not more than 2.0z (1 g, 1309C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Chlorhexidine Hy-drochloride, previously dried, dissolve in 2.0 mL of formic acid, add 60 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 14.46 mg of C22H30Cl2N10.2HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

chlorinated-lime
type: ChemicalDrugMonograph
pref label:
  en: Chlorinated Lime
  ja: サラシ粉
monograph id: JP18-chlorinated-lime
publisher: JP
status: Official
version: 18
definition:
  en: Chlorinated Lime contains not less than 30.
appearance:
  en: Chlorinated Lime occurs as a white powder. It has a chlorine-like odor. It dissolves partially in water. The solution changes red litmus paper to blue, then gradually decolorizes.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To Chlorinated Lime add dilute hydro-chloric acid: a gas, which has the odor of chlorine, evolves, and the gas changes moistened starch-potassium iodide paper to blue. (2) Shake 1 g of Chlorinated Lime with 10 mL of water, and filter: the filtrate responds to Qualitative Tests <1.09> (2) and (3) for calcium salt.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 5 g of Chlorinated Lime, transfer to a mortar, and triturate thoroughly with 50 mL of water. Transfer to a 500-mL volumetric flask with the aid of water, and add water to make 500 mL. Mix well, imme-diately take exactly 50 mL of the mixture in an iodine flask, add 10 mL of potassium iodide TS and 10 mL of dilute hy-drochloric acid, and titrate <2.50> the liberated iodine with 0.1 mol/L sodium thiosulfate VS (indicator: 3 mL of starch TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium thiosulfate VS ＝ 3.545 mg of Cl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant, and in a cold place.

chlormadinone-acetate
type: ChemicalDrugMonograph
pref label:
  en: Chlormadinone Acetate
  ja: クロルマジノン酢酸エステル
monograph id: JP18-chlormadinone-acetate
publisher: JP
status: Official
version: 18
molecular formula: C23H29ClO4
molecular weight: 404.93
appearance:
  en: Chlormadinone Acetate occurs as white to light yellow, crystals or crystalline powder. It is odorless. It is freely soluble in chloroform, soluble in acetonitrile, slightly soluble in ethanol (95) and in diethyl ether, and prac-tically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 2 mg of Chlormadinone Acetate in 1 mL of ethanol (95), and add 1 mL of 1,3-dinitrobenzene TS and 1 mL of a solution of potassium hy-droxide (1 in 5): a red-purple color develops. To 0.05 g of Chlormadinone Acetate add 2 mL of po-tassium hydroxide-ethanol TS, and boil on a water bath for 5 minutes. After cooling, add 2 mL of diluted sulfuric acid (2 in 7), and boil gently for 1 minute: the odor of ethyl ace-tate is perceptible. Determine the infrared absorption spectrum of Chlormadinone Acetate, previously dried, as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of previously dried Chlor-madinone Acetate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Chlormadinone Acetate as di-rected under Flame Coloration Test <1.04> (2): a green color ‌JP XVIII Official Monographs / Chlorobutanol 737 appears. D Optical rotation <2.49> [a]20: －10.0 – －14.09(after dry-ing, 0.2 g, acetonitrile, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Chlormadinone Acetate according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Chlormadinone Acetate according to Method 3, and per-form the test (not more than 2 ppm). Related substances—Dissolve 20 mg of Chlormadi-none Acetate in 10 mL of acetonitrile, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add acetonitrile to make exactly 100 mL, and use this solu-tion as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the total area of peaks other than the peak of chlormadinone acetate obtained from the sample solution is not larger than the peak area of chlor- visible Spectrophotometry <2.24>, and determine the absor-bances, AT and AS, at 285 nm. Amount (mg) of chlormadinone acetate (C23H29ClO4) ＝ MS × AT/AS MS: Amount (mg) of Chlormadinone Acetate RS taken
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

chlorobutanol
type: ChemicalDrugMonograph
pref label:
  en: Chlorobutanol
  ja: クロロブタノール
monograph id: JP18-chlorobutanol
publisher: JP
status: Official
version: 18
molecular formula: C4H7Cl3O
molecular weight: 177.46
definition:
  en: Chlorobutanol contains not less than 98.
appearance:
  en: Chlorobutanol occurs as colorless or white crystals. It has a camphoraceous odor. It is very soluble in methanol, in ethanol (95) and in diethyl ether, and slightly soluble in water. It slowly volatilizes in air. Melting point: not lower than about 769C.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Chlo-robutanol (1 in 200) add 1 mL of sodium hydroxide TS, then slowly add 3 mL of iodine TS: a yellow precipitate is pro-duced and the odor of iodoform is perceptible. (2) To 0.1 g of Chlorobutanol add 5 mL of sodium hy-droxide TS, shake well the mixture, add 3 to 4 drops of ani-line, and warm gently: the disagreeable odor of phenyl isoc-yanide (poisonous) is perceptible.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—Shake thoroughly 0.10 g of the pow-der of Chlorobutanol with 5 mL of water: the solution is neutral. (2) Chloride <1.03>—Dissolve 0.5 g of Chlorobutanol in 25 mL of dilute ethanol, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solu-tion as the test solution. Prepare the control solution with 1.0 mL of 0.01 mol/L hydrochloric acid VS by adding 25 mL of dilute ethanol, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.071z). Water <2.48> Not more than 6.0z (0.2 g, volumetric titra-tion, direct titration). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 20 mg each of Chlormadi-none Acetate and Chlormadinone Acetate RS, previously dried, and dissolve in ethanol (95) to make exactly 100 mL. Pipet 5 mL each of these solutions, to each add ethanol (95) to make exactly 100 mL, and use these solutions as the sam-ple solution and the standard solution, respectively. Perform the test with these solutions as directed under Ultraviolet- Description Chlorobutanol occurs as colorless or white crystals. It has a camphoraceous odor. It is very soluble in methanol, in ethanol (95) and in diethyl ether, and slightly soluble in water. It slowly volatilizes in air. Melting point: not lower than about 769C. Identification (1) To 5 mL of a solution of Chlo-robutanol (1 in 200) add 1 mL of sodium hydroxide TS, then slowly add 3 mL of iodine TS: a yellow precipitate is pro-duced and the odor of iodoform is perceptible. (2) To 0.1 g of Chlorobutanol add 5 mL of sodium hy-droxide TS, shake well the mixture, add 3 to 4 drops of ani-line, and warm gently: the disagreeable odor of phenyl isoc-yanide (poisonous) is perceptible. Purity (1) Acidity—Shake thoroughly 0.10 g of the pow-der of Chlorobutanol with 5 mL of water: the solution is neutral. (2) Chloride <1.03>—Dissolve 0.5 g of Chlorobutanol in 25 mL of dilute ethanol, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solu-tion as the test solution. Prepare the control solution with 1.0 mL of 0.01 mol/L hydrochloric acid VS by adding 25 mL of dilute ethanol, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.071z). Water <2.48> Not more than 6.0z (0.2 g, volumetric titra-tion, direct titration). Residue on ignition <2.44> Not more than 0.1z (1 g). Assay Transfer about 0.1 g of Chlorobutanol, accurately weighed, to a 200-mL conical flask, and dissolve in 10 mL of ethanol (95). Add 10 mL of sodium hydroxide TS, boil under a reflux condenser for 10 minutes, cool, add 40 mL of dilute nitric acid and exactly 25 mL o…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

chlorphenesin-carbamate
type: ChemicalDrugMonograph
pref label:
  en: Chlorphenesin Carbamate
  ja: クロルフェネシンカルバミン酸エステル
monograph id: JP18-chlorphenesin-carbamate
publisher: JP
status: Official
version: 18
molecular formula: C10H12ClNO4
molecular weight: 245.66
definition:
  en: Chlorphenesin Carbamate, when dried, contains not less than 98.
appearance:
  en: Chlorphenesin Carbamate occurs as white, crystals or a crystalline powder. It is freely soluble in methanol, in ethanol (95) and in pyri-dine, and slightly soluble in water. A solution of Chlorphenesin Carbamate in ethanol (95) (1 in 20) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Chlorphenesin Carbamate in ethanol (95) (3 in 200,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Chlorphenesin Carbamate, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Chlorphenesin Carbamate as directed under Flame Coloration Test <1.04> (2): a green color appears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Dissolve 2.0 g of Chlor-phenesin Carbamate in 20 mL of ethanol (95), and add 2 mL of dilute acetic acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the con-trol solution as follows: to 2.0 mL of Standard Lead Solu-tion add 20 mL of ethanol (95), 2 mL of dilute acetic acid and water to make 50 mL (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Chlorphenesin Carbamate according to Method 3, and perform the test (not more than 2 ppm). Chlorphenesin-2-carbamate—Dissolve 0.10 g of Chlorphenesin Carbamate in 20 mL of a mixture of hexane for liquid chromatography and 2-propanol (7:3), and use this solution as the sample solution. Perform the test with 10 mL of the sample solution as directed under Liquid Chroma-tography <2.01> according to the following conditions. De-termine the peak area, Aa, of chlorphenesin carbamate and the peak area, Ab, of chlorphenesin-2-carbamate by the au-tomatic integration method: the ratio, Ab/(Aa ＋ Ab), is not more than 0.007. Operating conditions— Detector: An ultraviolet absorption photometer (wave- System performance: Dissolve 0.1 g of Chlorphenesin Carbamate in 50 mL of methanol. To 25 mL of this solution add 25 mL of dilute sodium hydroxide TS, and warm at 609C for 20 minutes. To 20 mL of this solution add 5 mL of 1 mol/L hydrochloric acid TS, shake well with 20 mL of ethyl acetate, and allow to stand to separate the upper layer. When the procedure is run with 10 mL of this layer under the above operating conditions, chlorphenesin, chlorphenesin carbamate and chlorphenesin-2-carbamate are eluted in this order, with the relative retention times of chlorphenesin and chlorphenesin-2-carbamate to chlorphenesin carbamate being about 0.7 and about 1.2, respectively, and with the resolution between the peaks of chlorphenesin and chlor-phenesin carbamate being not less than 2.0. System repeatability: When the test is repeated 6 times with 10 mL…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Chlorphenesin Car-bamate, previously dried, dissolve in 20 mL of pyridine, add exactly 50 mL of 0.1 mol/L potassium hydroxide-ethanol TS, and warm at 709C for 40 minutes. After cooling, add 100 mL of ethanol (95), and titrate <2.50> the excess potas-sium hydroxide with 0.1 mol/L hydrochloric acid VS until ‌JP XVIII Official Monographs / Chlorphenesin Carbamate Tablets 739 the color of the solution changes from blue through blue-green to yellow (indicator: 1 mL of thymol blue TS). Per-form a blank determination in the same manner. Each mL of 0.1 mol/L potassium hydroxide-ethanol TS ＝ 24.57 mg of C10H12ClNO4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

chlorpheniramine-maleate
type: ChemicalDrugMonograph
pref label:
  en: Chlorpheniramine Maleate
  ja: クロルフェニラミンマレイン酸塩
monograph id: JP18-chlorpheniramine-maleate
publisher: JP
status: Official
version: 18
molecular formula: C16H19ClN2.C4H4O4
molecular weight: 390.86
cas number: 113-92-8
definition:
  en: Chlorpheniramine Maleate, when dried, contains not less than 98.
appearance:
  en: Chlorpheniramine Maleate occurs as white, fine crystals. It is very soluble in acetic acid (100), freely soluble in water and in methanol, and soluble in ethanol (99.5). It dissolves in dilute hydrochloric acid. A solution of Chlorpheniramine Maleate (1 in 20) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Chlorpheniramine Maleate in 0.1 mol/L hydro-chloric acid TS (3 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Chlorpheniramine Maleate RS prepared in the same manner as the sample solution: both spectra exhibit similar intensi-ties of absorption at the same wavelengths. Determine the infrared absorption spectrum of Chlorpheniramine Maleate, previously dried, as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of previously dried Chlorpheniramine Maleate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolve 0.10 g of Chlorpheniramine Maleate in 5 mL of methanol, and use this solution as the sample solution. Separately, dissolve 56 mg of maleic acid in 10 mL of metha-nol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solu-tion and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of diethyl ether, methanol, acetic acid (100) and water (70:20:7:3) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): a spot among two of the spots obtained with the sample solution shows the same intense and Rf value with the spot obtained with the standard solution. pH <2.54> Dissolve 1.0 g of Chlorpheniramine Maleate in 100 mL of freshly boiled and cooled water: the pH of this so-lution is between 4.0 and 5.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Chlorpheniramine Maleate in 50 mL of water: the solu-tion is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Chlor- pheniramine Maleate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.10 g of Chlor-pheniramine Maleate in 100 mL of the mobile phase, and use this solution as the sample solution. Pipet 3 mL of the sam-ple solution, and add the mobile phase to make exactly 100 mL. Pipet 2 mL of this solution, add the mobile phase to make exactly 20 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the area of the peak other than maleic acid and chlorpheniramine obtained from the sample solu-tion is not larger than 2/3 times the peak area of chlor-pheniramine from the standard solution, and the total area of the peaks other than maleic acid and chlorpheniramine from the sample solution is not larger than the peak area of chlorpheniramine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 225 nm). Column: A stainless steel column 3.9 mm in inside diame-ter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 8.57 g of ammonium dihydrogen-phosphate and 1 mL of phosphoric acid in water to make 1000 mL. To 800 mL of this solution add 200 mL of aceto-nitrile. Flow rate: Adjust so that the retention time of chlor-pheniramine is about 11 minutes. Time span of measurement: About 4 times as long as the retention time of chlorpheniramine, beginning after th…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Dissolve about 0.4 g of Chlorpheniramine Maleate, previously dried and accurately weighed, in 20 mL of acetic acid (100). Titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue-green to green (indicator: 2 drops of crystal violet TS). ‌JP XVIII Official Monographs / Chlorpheniramine Maleate Powder 741‌ Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 19.54 mg of C H ClN .C H O lution. Determine the absorbances AT and AS of the sample solution and standard solution at a wavelength of the maxi-mum absorbance at about 265 nm as directed under Ultravi-olet-visible Spectrophotometry <2.24>. 16 19 2 4 4 4
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

chlorpromazine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Chlorpromazine Hydrochloride
  ja: クロルプロマジン塩酸塩
monograph id: JP18-chlorpromazine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C17H19ClN2S.HCl
molecular weight: 355.33
appearance:
  en: Chlorpromazine Hydrochloride occurs as a white to pale yellow crystalline powder. It is odorless, or has a faint, characteristic odor. It is very soluble in water, freely soluble in ethanol (95) and in acetic acid (100), sparingly soluble in acetic anhy-dride, and practically insoluble in diethyl ether. It is gradually colored by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Chlorproma-zine Hydrochloride (1 in 1000) add 1 drop of iron (III) chlo-ride TS: a red color develops. Dissolve 0.1 g of Chlorpromazine Hydrochloride in JP XVIII Official Monographs / Chlorpromazine Hydrochloride Tablets 745 ‌20 mL of water and 3 drops of dilute hydrochloric acid, add 10 mL of 2,4,6-trinitrophenol TS, and allow to stand for 5 hours. Collect the resulting precipitate, wash with water, recrystallize from a small portion of acetone, and dry at 1059C for 1 hour: the crystals so obtained melt <2.60> be-tween 1759C and 1799C.‌ Dissolve 0.5 g of Chlorpromazine Hydrochloride in 5 mL of water, add 2 mL of ammonia TS, and heat on a water bath for 5 minutes. Cool, filter, and render the filtrate acidic with dilute nitric acid: the solution responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution of 1.0 g of Chlorpromazine Hydrochloride in 20 mL of water, when observed within 10 minutes, is clear and colorless to pale yellow. (2) Heavy metals <1.07>—Proceed with 1.0 g of Chlor- promazine Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Transfer an exactly measured volume of Chlor-promazine Hydrochloride Injection, equivalent to about pH <2.54> Dissolve 1.0 g of Chlorpromazine Hydrochlo- ride in 20 mL of freshly boiled and cooled water, and meas- 0.15 g of chlorpromazine hydrochloride (C 17H 19ClN2S.HCl) ure within 10 minutes: the pH of this solution is between 4.0 and 5.0. Purity (1) Clarity and color of solution—A solution of 1.0 g of Chlorpromazine Hydrochloride in 20 mL of water, when observed within 10 minutes, is clear and colorless to pale yellow. (2) Heavy metals <1.07>—Proceed with 1.0 g of Chlor- promazine Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g). Assay Weigh accurately about 0.7 g of Chlorpromazine Hydrochloride, previously dried, dissolve in 50 mL of a mix-ture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 35.53 mg of C17H19ClN2S.HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

chlorpropamide
type: ChemicalDrugMonograph
pref label:
  en: Chlorpropamide
  ja: クロルプロパミド
monograph id: JP18-chlorpropamide
publisher: JP
status: Official
version: 18
molecular formula: C10H13ClN2O3S
molecular weight: 276.74
definition:
  en: Chlorpropamide, when dried, contains not less than 98.
appearance:
  en: Chlorpropamide occurs as white, crystals or crystalline powder. It is freely soluble in methanol and in acetone, soluble in ethanol (95), and slightly soluble in diethyl ether, and practi-cally insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.08 g of Chlorpropamide in 50 mL of methanol. To 1 mL of the solution add 0.01 mol/L hydrochloric acid TS to make 200 mL. Determine the ab-sorption spectrum of the solution as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Chlorpropamide, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. Perform the test with Chlorpropamide as directed under Flame Coloration Test <1.04> (2): a green color ap-pears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—To 3.0 g Chlorpropamide add 150 mL of water, and warm at 709C for 5 minutes. Allow to stand in ice water for 1 hour, and filter. To 25 mL of the filtrate add 2 drops of methyl red TS and 0.30 mL of 0.1 mol/L sodium hydroxide VS: a yellow color develops. Chloride <1.03>—To 40 mL of the filtrate obtained in (1) add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Pre-pare the control solution with 0.25 mL of 0.01 mol/L hydro-chloric acid VS (not more than 0.011z). Sulfate <1.14>—To 40 mL of the filtrate obtained in add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solu-tion. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.021z). Heavy metals <1.07>—Proceed with 2.0 g of Chlor- propamide according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 0.6 g of Chlor-propamide in acetone to make exactly 10 mL, and use this Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, hours). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Chlorpropamide, previously dried, dissolve in 30 mL of neutralized ethanol, and add 20 mL of water. Titrate <2.50> with 0.1 mol/L so-dium hydroxide VS (indicator: 3 drops of phenolphthalein TS). Each mL of 0.1 mol/L sodium hydroxide VS ＝ 27.67 mg of C10H13ClN2O3S
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

cholesterol
type: ChemicalDrugMonograph
pref label:
  en: Cholesterol
  ja: コレステロール
monograph id: JP18-cholesterol
publisher: JP
status: Official
version: 18
molecular formula: C27H46O
molecular weight: 386.65
appearance:
  en: Cholesterol occurs as white to pale yellow, crystals or grains. It is odorless, or has a slight odor. It is tasteless. It is freely soluble in chloroform and in diethyl ether, spar-ingly soluble in ethanol (99.5) and in acetone, and practically insoluble in water. It gradually changes to a yellow to light yellow-brown color by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Cholesterol in 1 mL of chloroform, add 1 mL of sulfuric acid, and shake: a red color develops in the chloroform layer, and the sulfuric acid layer shows a green fluorescence. (2) Dissolve 5 mg of Cholesterol in 2 mL of chloroform, add 1 mL of acetic anhydride and 1 drop of sulfuric acid, and shake: a red color is produced, and it changes to green through blue. D Optical rotation <2.49> [a]25: －29 – －369(after drying, 0.2 g, acetone, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity of solution—Place 0.5 g of Cholesterol in a glass-stoppered flask, dissolve in 50 mL of warm ethanol (95), and allow to stand at room temperature for 2 hours: no turbidity or deposit is produced. (2) Acidity—Place 1.0 g of Cholesterol in a flask, dis-solve in 10 mL of diethyl ether, add 10.0 mL of 0.1 mol/L sodium hydroxide VS, and shake for 1 minute. Expel the diethyl ether, and boil for 5 minutes. Cool, add 10 mL of water, and titrate <2.50> with 0.05 mol/L sulfuric acid VS (indicator: 2 drops of phenolphthalein TS). Perform a blank determination in the same manner. The volume of 0.1 mol/L sodium hydroxide VS consumed is not more than 0.30 mL. Loss on drying <2.41> Not more than 0.30z (1 g, in vacu-um, 609C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
storage conditions:
  en: Containers—Hermetic containers.
type: PharmacopoeiaMonograph

chorionic-gonadotrophin
type: ChemicalDrugMonograph
pref label:
  en: Chorionic Gonadotrophin
  ja: ヒト絨毛性性腺刺激ホルモン
monograph id: JP18-chorionic-gonadotrophin
publisher: JP
status: Official
version: 18
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant, and in a cold place.
type: PharmacopoeiaMonograph

chotosan-extract
type: ChemicalDrugMonograph
pref label:
  en: Chotosan Extract
  ja: 釣藤散エキス
monograph id: JP18-chotosan-extract
publisher: JP
status: Official
version: 18
definition:
  en: Chotosan Extract contains not less than 24 mg and not more than 72 mg of hesperidin, not less than 6 mg and not more than 18 mg of glycyrrhizic acid (C42H62O16: 822.
appearance:
  en: Chotosan Extract is a light brown to yellow-brown powder or black-brown viscous extract. It has a slight odor, and has a pungent and slightly sweet first, then bitter taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Shake 2.0 g of the dry extract (or 6.0 g of the viscous extract) with 20 mL of water and 2 mL of am-monia TS, add 20 mL of diethyl ether, and shake. Separate the diethyl ether layer, evaporate the solvent under low pres-sure (in vacuo), add 1 mL of methanol to the residue, and use this solution as the sample solution. Separately, dissolve 1 mg each of rhyncophylline for thin-layer chromatography and hirsutine for thin-layer chromatography in 1 mL of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL of the sample so-lution and 2 mL of the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatogra-phy. Develop the plate with a mixture of ethyl acetate, 1-propanol, water and acetic acid (100) (7:5:4:1) to a distance of about 7 cm, and air-dry the plate. Examine under ultravi-olet light (main wavelength: 254 nm): one of the several spots obtained from the sample solution has the same color tone and Rf value with one of the two dark purple spots Chotosan Extract / Crude Drugs and Related Drugs from the standard solution (Uncaria Hook). Shake 2.0 g of the dry extract (or 6.0 g of the viscous extract) with 10 mL of water, add 10 mL of 1-butanol, shake, centrifuge, and use the 1-butanol layer as the sample solution. Separately, dissolve 1 mg of hesperidin for thin-layer chromatography in 1 mL of methanol, and use this so-lution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 20 mL of the sample solution and 10 mL of the standard solution on a plate of silica gel for thin-layer chro-matography. Develop the plate with a mixture of ethyl ace-tate, acetone, water and acetic acid (100) (10:6:3:1) to a dis-tance of about 7 cm, and air-dry the plate. Spray evenly 2,6-dibromo-N-chloro-1,4-benzoquinone monoimine TS on the plate, and allow to stand in an ammonia g…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Prepare the test solution with 1.0 g of the dry extract (or an amount of the viscous ex-tract, equivalent to 1.0 g of the dried substance) as directed under Extracts (4), and perform the test (not more than 30 ppm). (2) Arsenic <1.11>—Prepare the test solution with 0.67 g of the dry extract (or an amount of the viscous extract, equivalent to 0.67 g of the dried substance) according to Method 3, and perform the test (not more than 3 ppm). Loss on drying <2.41> The dry extract: Not more than 7.5z (1 g, 1059C, 5 hours). The viscous extract: Not more than 66.7z (1 g, 1059C, 5 hours). minutes, centrifuge, and take the supernatant liquid. To the residue add 20 mL of diluted methanol (1 in 2), shake for 5 minutes, centrifuge, and take the supernatant liquid. Com-bine these supernatant liquids, add diluted methanol (1 in 2) to make exactly 50 mL, and use this solution as the sample solution. Separately, weigh accurately about 10 mg of Glycyrrhizic Acid RS (separately determine the water <2.48> by coulometric titration, using 10 mg), dissolve in diluted methanol (1 in 2) to make exactly 100 mL, and use this solu-tion as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of glycyrrhizic acid in each solution. Total ash <5.01> Not more than 15.0z, calculated on the dried basis. Amount (mg) of glycyrrhizic acid (C ＝ MS × AT/AS × 1/2 42H 62O 16)
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Hesperidin—Weigh accurately about 0.1 g of the dry extract (or an amount of the viscous extract, equiva-lent to about 0.1 g of dried substance), add exactly 50 mL of diluted tetrahydrofuran (1 in 4), shake for 30 minutes, cen-trifuge, and use the supernatant liquid as the sample solu-tion. Separately, weigh accurately about 10 mg of hesperidin for assay, previously dried in a desiccator (silica gel) for 24 hours, dissolve in methanol to make exactly 100 mL. Pipet 10 mL of this solution, add diluted tetrahydrofuran (1 in 4) to make exactly 100 mL, and use this solution as the stand-ard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of hesperidin in each solution. MS: Amount (mg) of Glycyrrhizic Acid RS taken, calcu-lated on the anhydrous basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 3.85 g of ammonium acetate in 720 mL of water, and add 5 mL of acetic acid (100) and 280 mL of acetonitrile. Flow rate: 1.0 mL per minute (the retention time of glycyr- Amount (mg) of hesperidin ＝ MS × AT/AS × 1/20 rhizic acid is about 15 minutes). System suitability— MS: Amount (mg) of hesperidin for assay taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 285 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of water, acetonitrile and acetic acid (100) (82:…
storage conditions:
  en: Containers—Tight containers.

cibenzoline-succinate
type: ChemicalDrugMonograph
pref label:
  en: Cibenzoline Succinate
  ja: シベンゾリンコハク酸塩
monograph id: JP18-cibenzoline-succinate
publisher: JP
status: Official
version: 18
molecular formula: C18H18N2.C4H6O4
molecular weight: 380.44
cas number: 100678-32-8
definition:
  en: Cibenzoline Succinate, when dried, contains not less than 98.
appearance:
  en: Cibenzoline Succinate occurs as a white crys-talline powder. It is freely soluble in methanol and in acetic acid (100), and sparingly soluble in water and in ethanol (99.5). A solution of Cibenzoline Succinate in methanol (1 in 10) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cibenzoline Succinate (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cibenzoline Succinate as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare the spec-trum with the Reference Spectrum: both spectra exhibit simi-lar intensities of absorption at the same wave numbers. Shake 0.4 g of Cibenzoline Succinate with 2.5 mL of sodium hydroxide TS and 5 mL of ethyl acetate, allow to stand, and to 1 mL of the water layer so obtained add 0.5 mL of 1 mol/L hydrochloric acid TS and 0.5 mL of iron (III) chloride TS: a blown precipitate is formed.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution ob-tained by dissolving 0.20 g of Cibenzoline Succinate in 10 mL of water is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Cibenzo- line Succinate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Cibenzoline Succinate according to Method 3, using a so-lution of magnesium nitrate hexahydrate in ethanol (95) (1 in 25), and perform the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of Cibenzoline Succinate in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add methanol to make exactly 100 mL. Pipet 5 mL and 2 mL of this solution, add methanol to make them exactly 10 mL, and use these solutions as the standard solution (1) and the standard solution (2). Perform the test with these solutions and (2) on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, methanol and ammonia solution (28) (20:3:2) to a distance of about 10 cm, air-dry the plate, and dry more at 809C for 30 minutes. After cooling, examine under ultraviolet light (main wavelength: 254 nm): the spot other than the principal spot obtained from the sample solu-tion is not more intense than the spot from the standard so-lution (1). Allow the plate to stand for 30 minutes in iodine vapor: the spot other than the principal spot from the sample solution is not more intense than the spot from the standard solution (1), and the spot, which is more intense than the spot from the standard solution (2), is not more than two. Loss on drying <2.41> Not more than 0.3z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Cibenzoline Suc-cinate, previously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from violet to blue-green through blue (indicator: 2 drops of crystal violet TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 38.04 mg of C18H18N2.C4H6O4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

ciclacillin
type: ChemicalDrugMonograph
pref label:
  en: Ciclacillin
  ja: シクラシリン
monograph id: JP18-ciclacillin
publisher: JP
status: Official
version: 18
molecular formula: C15H23N3O4S
molecular weight: 341.43
cas number: 3485-14-1
definition:
  en: Ciclacillin contains not less than 920 mg (potency) and not more than 1010 mg (potency) per mg, calcu-lated on the anhydrous basis.
appearance:
  en: Ciclacillin occurs as white to light yellow-white crystalline powder. It is sparingly soluble in water, slightly soluble in metha-nol, and practically insoluble in acetonitrile and in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Ciclacillin as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec-trum of Ciclacillin RS: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋300 – ＋3159(2 g, water, Amount (mg) of cibenzoline succinate (C18H18N2.C4H6O4) ＝ MS × QT/QS MS: Amount (mg) of cibenzoline succinate for assay taken Internal standard solution—Dissolve 0.1 g of 2-ethylhexyl parahydroxybenzoate in methanol to make 100 mL. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 5 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 2.67 g of sodium di-2-ethylhexyl 100 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Ciclacillin according to Method 2, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 20 ppm). (2) Arsenic <1.11>—Prepare the test solution with 1.0 g of Ciclacillin according to Method 3, and perform the test (not more than 2 ppm). Water <2.48> Not more than 2.0z (1 g, volumetric titra-tion, direct titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Ciclacillin and Ciclacillin RS, equivalent to about 50 mg (potency), dissolve each in a suitable amount of the mobile phase, add exactly 5 ‌mL of the internal standard solution and the mobile phase to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of ciclacillin to that of the internal standard. culated on the dried basis. Description Ciclosporin occurs as a white powder. It is very soluble in acetonitrile, in methanol and in ethanol (95), freely soluble in diethyl ether, and practically insoluble in water. Identification Determine the infrared absorption spectrum Amount [ mg (potency)] of ciclacillin (C ＝ MS × QT/QS × 1000 15H23N3O4S) of Ciclosporin as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec- MS: Amount [mg (potency)] of Ciclacillin RS taken Internal standard solution—A solution of orcin in the mo-bile phase (1 in 500). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 0.771 g of ammonium acetate in about 900 mL of water, adjust the pH to 4.0 with acetic acid (100), and add water to make 1000 mL. To 850 mL of this solution add 150 mL of acetonitrile. Flow rate: Adjust so that the retention time of ciclacillin is about 4 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, ciclacillin and t…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

ciclosporin
type: ChemicalDrugMonograph
pref label:
  en: Ciclosporin
  ja: シクロスポリン
monograph id: JP18-ciclosporin
publisher: JP
status: Official
version: 18
cas number: 59865-13-3
definition:
  en: Ciclosporin according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Use the sample solution ob-tained in the Assay as the sample solution. Pipet 2 mL of the sample solution, add a mixture of water and acetonitrile (1:1) to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard soluton as directed un-der Liquid Chromatography <2.01> according to the follow-ing conditions. Determine each peak area of both solutions by the automatic integration method: the area of the peak other than the ciclosporin obtained from the sample solution is not larger than 7/10 times the peak area of ciclosporin from the standard solution, and the total area of all peaks other than the ciclosporin from the sample solution is not larger than 1.5 times the peak area of ciclosporin from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 2 times as long as the retention time of ciclosporin, beginning after the solvent peak. System suitability— C62H N11O 12: 1202.61 System performance: Proceed as directed in the system suitability in the Assay. cyclo{-[(2S,3R,4R,6E )-3-Hydroxy-4-methyl-2- methylaminooct-6-enoyl]-L-2-aminobutanoyl- N-methylglycyl-N-methyl-L-leucyl-L-valyl-N-methyl- L-leucyl-L-alanyl-D-alanyl-N-methyl-L-leucyl-N-methyl-L-leucyl-N-methyl-L-valyl-} [59865-13-3] Ciclosporin contains not less than 98.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Ciclosporin in 10 mL of ethanol (95): the solution is clear, and has no more color than the following control solutions (1), (2) or (3). Control solution (1): To exactly 3.0 mL of Iron (III) Chlo-ride CS and exactly 0.8 mL of Cobalt (II) Chloride CS add diluted hydrochloric acid (1 in 40) to make exactly 100 mL. Control solution (2): To exactly 3.0 mL of Iron (III) Chlo-ride CS, exactly 1.3 mL of Cobalt (II) Chloride CS and ex-actly 0.5 mL of Copper (II) Sulfate CS add diluted hydro- chloric acid (1 in 40) to make exactly 100 mL. Control solution (3): To exactly 0.5 mL of Iron (III) Chlo-ride CS and exactly 1.0 mL of Cobalt (II) Chloride CS add diluted hydrochloric acid (1 in 40) to make exactly 100 mL. Heavy metals <1.07>—Proceed with 1.0 g of Ciclosporin according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Use the sample solution ob-tained in the Assay as the sample solution. Pipet 2 mL of the sample solution, add a mixture of water and acetonitrile (1:1) to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard soluton as directed un-der Liquid Chromatography <2.01> according to the follow-ing conditions. Determine each peak area of both solutions by the automatic integration method: the area of the peak other than the ciclosporin obtained from the sample solution is not larger than 7/10 times the peak area of ciclosporin from the standard solution, and the total area of all peaks other than the ciclosporin from the sample solution is not larger than 1.5 times the peak area of ciclosporin from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 2 times as long as the rete…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 30 mg each of Ciclosporin and Ciclosporin RS (separately determine the loss on drying <2.41> under the same conditions as Ciclosporin), and dis- solve each in a mixture of water and acetonitrile (1:1) to make exactly 25 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of ciclosporin in each solution. Amount (mg) of ciclosporin (C62H111N11O12) ＝ MS × AT/AS MS: Amount (mg) of Ciclosporin RS taken, calculated on the dried basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm). Column: A stainless steel column 4 mm in inside diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Con-nect the sample injection port and the column with a stain-less steel tube 0.3 mm in inside diameter and 1 m in length. Column temperature: A constant temperature of about 809C (including the sample injection port and the connecting tube). Mobile phase: A mixture of water, acetonitrile, tert-butyl methyl ether and phosphoric acid (520:430:50:1). Flow rate: Adjust so that the retention time of ciclosporin is about 27 minutes. System suitability— System performance: Dissolve 3 mg of Ciclosporin U in 2.5 mL of a mixture of water and acetonitrile (1:1), and add 2.5 mL of the standard solution. When the procedure is run with 20 mL of this solution under the above operating condi-tions, ciclosporin U and ciclosporin are eluted in this order with the resolution between these peaks being not less than 1.2. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of ciclosporin is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cilazapril-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Cilazapril Hydrate
  ja: シラザプリル水和物
monograph id: JP18-cilazapril-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C22H31N3O5.H2O
molecular weight: 435.51
cas number: 92077-78-6
definition:
  en: Cilazapril Hydrate contains not less than 98.
appearance:
  en: Cilazapril Hydrate occurs as white to yellowish white, crystals or crystalline powder. It is very soluble in methanol, freely soluble in ethanol (99.5) and in acetic acid (100), and slightly soluble in water. It gradually turns yellow on exposure to light. Melting point: about 1019C (with decomposition). with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, methanol, acetic acid (100), hexane, and water (62:15:10:10:3) to a dis-tance of about 15 cm, and air-dry the plate. Leave the plate in iodine vapor for 2 hours, and examine the plate under ul-traviolet light (main wavelength: 254 nm): of the spots other than the principal spot with an Rf value close to 0.40 ob-tained from the sample solution, the spot in the vicinity of Rf value 0.17 is not more intense than the spot from the standard solution (1), and the spot in the vicinity of Rf value 0.44 is not more intense than the spot from the standard so-lution (2). The number of all other spot does not exceed 3, and of these spots, no more than one is more intense than the spot from the standard solution (3) and none are more intense than the spot from the standard solution (2). Water <2.48> 3.5 – 5.0z (0.3 g, volumetric titration, direct titration). Residue on ignition <2.44> Not more than 0.1z (0.5 g).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 4 mL of a solution of Cilazapril Hy-drate (1 in 1000) add 2 mL of Dragendorff's TS: an orange precipitate is produced. (2) Determine the infrared absorption spectrum of Cilazapril Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －53 – －589(0.2 g calculated on the anhydrous basis, methanol, 20 mL, 100 mm).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Cilazapril Hydrate, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.02 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.02 mol/L perchloric acid VS ＝ 8.350 mg of C H N O 22 31 3 5 Identification (1) To 4 mL of a solution of Cilazapril Hy-drate (1 in 1000) add 2 mL of Dragendorff's TS: an orange precipitate is produced. (2) Determine the infrared absorption spectrum of Cilazapril Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －53 – －589(0.2 g calculated on the anhydrous basis, methanol, 20 mL, 100 mm).
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cilnidipine
type: ChemicalDrugMonograph
pref label:
  en: Cilnidipine
  ja: シルニジピン
monograph id: JP18-cilnidipine
publisher: JP
status: Official
version: 18
molecular formula: C27H28N2O7
molecular weight: 492.52
cas number: 132203-70-4
definition:
  en: Cilnidipine, when dried, contains not less than 98.
appearance:
  en: Cilnidipine occurs as a faint yellow crystalline powder. It is freely soluble in acetonitrile, sparingly soluble in methanol and in ethanol (99.5), and practically insoluble in water. A solution of Cilnidipine in acetonitrile (1 in 100) shows no optical rotation. It is gradually colored to reddish yellow and decomposed by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cilnidipine in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cilnidipine RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of previ-ously dried Cilnidipine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of dried Cilnidipine RS: both spectra exhibit simi-lar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Cilnidipine according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Conduct this procedure using light-resistant vessels. Dissolve 50 mg of Cilnidipine in 20 mL of acetonitrile, add the mobile phase to make 100 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Per-form the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and de-termine each peak area by the automatic integration method: the area of the peak, having the relative retention time of about 0.5 to cilnidipine, obtained from the sample solution is not larger than 2/5 times the peak area of cilnidipine from the standard solution, the area of the peaks other than cil-nidipine and the above mentioned peak from the sample so-lution is not larger than 1/5 times the peak area of cilnidi-pine from the standard solution, and the total area of the peaks other than cilnidipine from the sample solution is not larger than the peak area of cilnidipine from the standard so-lution. For the area of the peak, having the relative retention time of about 1.15, about 1.6, and about 1.7 to cilnidipine, multiply the correction factor, 1.5, 1.4, and 1.6, respectively. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 3 times as long as the retention time of cilnidipine, beginning after the solvent peak. System suitability— System performance: Proceed as directed in the system suitability in the Assay. Test for required detectability: Pipet 5 mL of the standard solution, add the mobile phase to make exactly 50 mL. Con…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Conduct this procedure using light-resistant vessels. Weigh accurately about 50 mg each of Cilnidipine and Cil-nidipine RS, both previously dried, dissolve in 20 mL of acetonitrile, and add the mobile phase to make exactly 100 mL, respectively. Pipet 5 mL each of these solutions, add ex-actly 5 mL of the internal standard solution, add the mobile phase to make 25 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 10 mL each of the sample solution and standard so-lution as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and calculate the ratios, QT and QS, of the peak area of cilnidipine to that of the in-ternal standard. Amount (mg) of cilnidipine (C27H28N2O7) ＝ MS × QT/QS MS: Amount (mg) of Cilnidipine RS taken Internal standard solution—A solution of butyl parahy- ‌758 droxybenzoate in acetonitrile (1 in 1000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 240 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with perfluorohexylpropyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 1.36 g of sodium acetate trihydrate in water to make 1000 mL, and adjust to pH 5.5 with diluted acetic acid (100) (1 in 100). To 400 mL of this solution add 600 mL of methanol. Flow rate: Adjust so that the retention time of cilnidipine is about 20 minutes. System suitability— System performance: After exposing Cilnidipine to a fluo-rescent light (15,000 lx･h), take 10 mg, dissolve in 4 mL of acetonitrile, and add the mobile phase to make 20 mL. When the procedure is run with 10 mL of this solution under the above operating conditions, the resolution between the peak of cilnidipine and the peak having the relative retention time of about 1.07 to cilnidipine is not less than 1.5. System repeatability: Wh…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cilostazol
type: ChemicalDrugMonograph
pref label:
  en: Cilostazol
  ja: シロスタゾール
monograph id: JP18-cilostazol
publisher: JP
status: Official
version: 18
molecular formula: C20H27N5O2
molecular weight: 369.46
cas number: 73963-72-1
definition:
  en: Cilostazol, when dried, contains not less than 98.
appearance:
  en: Cilostazol occurs as white to pale yellow-white, crystals or crystalline powder. It is slightly soluble in methanol, in ethanol (99.5) and in acetonitrile, and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cilostazol in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Cilostazol RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Cilostazol as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the Amount (mg) of cilnidipine (C 27H28N2O7) ＝ M S × QT/QS spectrum with the Reference Spectrum or the spectrum of Cilostazol RS: both spectra exhibit similar intensities of ab- MS: Amount (mg) of Cilnidipine RS taken sorption at the same wave numbers.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 50 mg each of Cilostazol and Cilostazol RS, previously dried, dissolve each in a suita-ble amount of methanol, add exactly 5 mL of the internal standard solution and methanol to make 50 mL. To 1 mL each of these solutions add methanol to make 10 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of cilostazol to that of the internal standard. Amount (mg) of cilostazol (C20H27N5O2) ＝ MS × QT/QS MS: Amount (mg) of Cilostazol RS taken Internal standard solution—A solution of benzophenone in methanol (1 in 250). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of water, acetonitrile and metha-nol (10:7:3). Flow rate: Adjust so that the retention time of cilostazol is about 9 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, cilostazol and the internal standard are eluted in this order with the resolution between these peaks being not less than 9. System repeatability: When the test is repeated 5 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratio of the peak area of cilostazol to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

cimetidine
type: ChemicalDrugMonograph
pref label:
  en: Cimetidine
  ja: シメチジン
monograph id: JP18-cimetidine
publisher: JP
status: Official
version: 18
molecular formula: C10H16N6S
molecular weight: 252.34
cas number: 51481-61-9
definition:
  en: Cimetidine, when dried, contains not less than 99.
appearance:
  en: Cimetidine occurs as a white crystalline pow-der. It is odorless, and has a bitter taste. It is freely soluble in methanol and in acetic acid (100), sparingly soluble in ethanol (95), slightly soluble in water, and practically insoluble in diethyl ether. It dissolves in dilute hydrochloric acid. It is gradually colored by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 0.1 mL of a solution of Cimetidine in ethanol (95) (1 in 100) add 5 mL of citric acid-acetic anhy-dride TS, and heat in a water bath for 15 minutes: a red-purple color develops. (2) Determine the infrared absorption spectrum of Cimetidine, previously dried, as directed in the potassium bromide disk method under the Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. pH <2.54> Dissolve 0.5 g of Cimetidine in 50 mL of freshly boiled and cooled water, shake for 5 minutes and filter: the pH of the filtrate is between 9.0 and 10.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Cimetidine in 10 mL of methanol: the solution is clear and colorless to pale yellow in color. Heavy metals <1.07>—Proceed with 2.0 g of Cimeti- dine according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Amount (mg) of cilostazol (C 20H27N5O2) ＝ M S × QT/QS Arsenic <1.11>—Dissolve 1.0 g of Cimetidine in 5 mL of dilute hydrochloric acid, and perform the test with this so- ‌762 lution (not more than 2 ppm). ‌Related substances—Dissolve 0.5 g of Cimetidine in 10 mL of methanol, and use this solution as the sample solu-tion. Pipet 1 mL of the sample solution, add methanol to make exactly 100 mL. Pipet 1 mL of this solution, add meth-anol to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 4 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, methanol and am-monia solution (28) (21:2:2) to a distance of about 15 cm, air-dry the plate, and then dry at 809C for 30 minutes. Allow the plate to stand in iodine vapor for 45 minutes: the spots other than the principal spot obtained from the sample solu-tion are not more intense than the spot from the standard so-lution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.24 g of Cimetidine, previ-ously dried, dissolve in 75 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 25.23 mg of C10H16N6S
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

cinchocaine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cinchocaine Hydrochloride
  ja: ジブカイン塩酸塩
monograph id: JP18-cinchocaine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C20H29N3O2.HCl
molecular weight: 379.92
appearance:
  en: Dibucaine Hydrochloride occurs as white, crystals or crystalline powder. It is very soluble in water, in ethanol (95) and in acetic acid (100), freely soluble in acetic anhydride, and practically in-soluble in diethyl ether. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Dibucaine Hydrochloride in 1 mol/L hydrochlo-ric acid TS (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dibucaine Hydrochloride, previously dried, as directed in the potassium bromide disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Dibucaine Hydrochloride (1 in 10) responds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Dibucaine Hydrochloride in 50 mL of water: the pH of this solution is between 5.0 and 6.0. nation, and dry in vacuum over phosphorus (V) oxide at 809C for 5 hours. Seal immediately the open end of the tube, and determine the melting point.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Dibucaine Hydrochloride in 20 mL of water: the solution is clear and colorless. Determine the absorbance of this solu-tion at 430 nm as directed under Ultraviolet-visible Spectro-photometry <2.24>, using water as the blank: it is not more than 0.03. Sulfate <1.14>—Perform the test with 0.30 g of Dibucaine Hydrochloride. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.056z). Heavy metals <1.07>—Proceed with 1.0 g of Dibucaine Hydrochloride according to Method 1, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.20 g of Dibucaine Hydrochloride in 5 mL of ethanol (95), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add ethanol (95) to make exactly 20 mL, then pipet 2 mL of this solution, add ethanol (95) to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chroma-tography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chro-matography. Develop the plate with a mixture of ethyl acetate, water and acetic acid (100) (3:1:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultravio-let (main wavelength: 254 nm): the spots other than the prin-cipal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 2.0z (1 g, in vacu-um, phosphorus (V) oxide, 809C, 5 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Dibucaine Hydro-chloride, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 19.00 mg of C20H29N3O2.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cinoxacin
type: ChemicalDrugMonograph
pref label:
  en: Cinoxacin
  ja: シノキサシン
monograph id: JP18-cinoxacin
publisher: JP
status: Official
version: 18
molecular formula: C12H10N2O5
molecular weight: 262.22
cas number: 28657-80-9
definition:
  en: Cinoxacin, when dried, contains not less than 98.
appearance:
  en: Cinoxacin occurs as a white to pale yellow crystalline powder. It is odorless or has a slight, characteris-tic odor. It has a bitter taste. It is slightly soluble in N,N-dimethylformamide and in acetone, very slightly soluble in ethanol (99.5), and practi-cally insoluble in water. It dissolves in sodium hydroxide TS. Melting point: about 2659C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 30 mg of Cinoxacin in 10 mL of dilute sodium hydroxide TS, and add water to make 100 mL. To 1 mL of this solution add 0.1 mol/L hydrochloric acid TS to make 50 mL. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref- erence Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cinoxacin as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfate <1.14>—Dissolve 0.20 g of Cinoxacin in 10 mL of dilute sodium hydroxide TS, add 20 mL of 0.1 mol/L hydrochloric acid TS, shake, filter, and add water to the filtrate to make 50 mL. Perform the test using this solu-tion as the test solution. Prepare the control solution with 0.20 mL of 0.005 mol/L sulfuric acid VS by adding 10 mL of dilute sodium hydroxide TS, 20 mL of 0.1 mol/L hydrochlo-ric acid TS, and water to make 50 mL (not more than 0.048z). Heavy metals <1.07>—Proceed with 1.0 g of Cinoxa- cin according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 10 mg of Cinoxacin in 10 mL of acetone, and use this solution as the sample solu-tion. Pipet 1 mL of the sample solution, add acetone to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatog-raphy. Develop the plate with a mixture of acetonitrile, water and ammonia solution (28) (14:4:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultravio-let light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 1 hour). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Cinoxacin, previ-ously dried, add 60 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and dissolve by warming. After cool-ing, titrate <2.50> with 0.1 mol/L perchloric acid VS (poten-tiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 26.22 mg of C12H10N2O5
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

ciprofloxacin-hydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Ciprofloxacin Hydrochloride Hydrate
  ja: シプロフロキサシン塩酸塩水和物
monograph id: JP18-ciprofloxacin-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
definition:
  en: Ciprofloxacin Hydrochloride Hydrate contains not less than 98.
appearance:
  en: Ciprofloxacin Hydrochloride Hydrate occurs as a white to pale yellow crystalline powder. It is sparingly soluble in water, slightly soluble in metha-nol, and very slightly soluble in ethanol (99.5). It is gradually colored to a slightly brownish light yellow by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of Ciprofloxacin Hydrochloride Hydrate, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Conduct this procedure using light-resistant vessels. Dissolve 50 mg of Ciprofloxacin Hydrochloride Hydrate in 5 mL of water, and use this solution as the sample solution. Separately, dissolve 45 mg of Ciprofloxacin RS in 5 mL of ammonia TS, and use this solution as the standard solution. Perform the test with these solutions, as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. After allowing to stand the plate in the vapor of ammonia for 15 minutes, develop the plate with a mixture of metha-nol, dichloromethane, ammonia solution (28) and aceto-nitrile (4:4:2:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the principal spot obtained from the sample solution and the spot obtained from the standard solution show the same Rf value. A solution of Ciprofloxacin Hydrochloride Hydrate (1 in 500) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfate <1.14>—Perform the test with 0.5 g of Ciprofloxacin Hydrochloride Hydrate. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.048z). Heavy metals <1.07>—Proceed with 1.0 g of Ciprofloxacin Hydrochloride Hydrate according to Method 2, and perform the test. Prepare the control solution with 1.0 ml of Standard Lead Solution (not more than 10 ppm). Fluoroquinolonic acid—Conduct this procedure using light-resistant vessels. Dissolve 50 mg of Ciprofloxacin Hydrochloride Hydrate in water to make exactly 5 mL, and use this solution as the sample solution. Separately, dissolve 10 mg of fluoroquinolonic acid for thin-layer chromatogra- phy in 0.1 mL of ammonia TS and water to make exactly 100 mL. Pipet 2 mL of this solution, add water to make exactly 10 mL, and use this solution as the standard solution. Per-form the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. After allowing to stand the plate in the vapor of ammonia for 15 minutes, develop the plate with a mixture of methanol, dichloromethane, ammonia solution (28) and acetonitrile (4:4:2:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot obtained from the sample solution, corresponding to the spot from the standard solution, is not more intense than that from the standard solution. Related substances—Conduct this procedure using light-resistant vessels. Dissolve 25 mg of Ciprofloxacin Hy-drochloride Hydrate in 50 mL of mobile phase, and use this solution as the sample solution. Pipet 2 mL of the sample so-lution, add the mobile phase to make exactly 20 mL. Pipet 1 mL of this solution, add the mobile phase to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 50 mL each of the sampl…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Conduct this procedure using light-resistant vessels. Weigh accurately about 25 mg of Ciprofloxacin Hydrochlo-ride Hydrate, dissolve in the mobile phase to make exactly 50 mL, and use this solution as the sample solution. Separately, weigh accurately about 22.5 mg of Ciprofloxacin RS, previ- ‌766 ously dried at 1209C in vacuum for 6 hours, add 2 mL of a mixture of water and phosphoric acid (13:1), then add the mobile phase to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing operating conditions, and determine the peak areas, AT and AS, of ciprofloxacin in each solution. Amount (mg) of ciprofloxacin hydrochloride (C H FN O .HCl)＝ M × A /A × 1.110 the spectrum with the Reference Spectrum or the spectrum of a solution of Cisplatin RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cisplatin as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Cisplatin RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. 17 18 3 3 S T S A solution of Cisplatin (1 in 2000) responds to MS: Amount (mg) of Ciprofloxacin RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 278 nm). Column: A stainless steel column 4 mm in inside diameter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: To 2.88 g of phosphoric acid add water to make 1000 mL, and adjust to pH 3.0 with triethylamine. To 870 mL of this solution add 130 mL of acetonitrile for liquid chromatography. Flow rate:…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

ciprofloxacin
type: ChemicalDrugMonograph
pref label:
  en: Ciprofloxacin
  ja: シプロフロキサシン
monograph id: JP18-ciprofloxacin
publisher: JP
status: Official
version: 18
molecular formula: C17H18FN3O3
molecular weight: 331.34
cas number: 85721-33-1
definition:
  en: Ciprofloxacin, when dried, contains not less than 98.
appearance:
  en: Ciprofloxacin occurs as a white to light yellow-white, crystalline powder. It is practically insoluble in water and in ethanol (99.5). It dissolves in ammonia TS. It is gradually colored to yellow tint by light. Melting point: about 2709C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of Ciprofloxacin, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of the Ciprofloxacin RS: both spectra exhibit simi-lar intensities of absorption at the same wave numbers. (2) Conduct this procedure using light-resistant vessels. Dissolve 50 mg each of Ciprofloxacin and Ciprofloxacin RS in 5 mL of ammonia TS, and use these solutions as the sam-ple solution and the standard solution, respectively. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solu- tion and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. After allowing to stand this plate in the vapor of ammonia for 15 minutes, develop the plate with a mixture of methanol, dichloromethane, ammonia solution (28) and acetonitrile (4:4:2:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the principal spot obtained from the sample solution and the spot from the standard solution show the same Rf value.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—To 1.5 g of Ciprofloxacin add 75 mL of water, and boil for 5 minutes. After cooling, add water to make 75 mL, and filter. To 25 mL of the fil-trate add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 0.30 mL of 0.01 mol/L hydrochloric acid VS add 6 mL of dilute sulfuric acid and water to make 50 mL (not more than 0.021z). Heavy metals <1.07>—Proceed with 2.0 g of Ciprofloxacin according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Fluoroquinolonic acid—Conduct this procedure using light-resistant vessels. Dissolve 50 mg of Ciprofloxacin in ammonia TS to make exactly 5 mL, and use this solution as the sample solution. Separately, dissolve 10 mg of fluoro-quinolonic acid for thin-layer chromatography in 0.1 mL of ammonia TS and water to make exactly 100 mL. Pipet 2 mL of this solution, add water to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 5 mL each of the sample solution and the standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. After allowing to Time span of measurement: About 2.3 times as long as the retention time of ciprofloxacin, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 5 mL of the standard solution, and add the mobile phase to make exactly 20 mL. Confirm that the peak area of ciprofloxacin obtained with 50 mL of this solution is equivalent to 20 to 30z of that with 50 mL of the standard solution. System performance: When the procedure is run with 50 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of ciprofloxacin are not less than 3500 and not more th…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Conduct this procedure using light-resistant vessels. Weigh accurately about 25 mg each of Ciprofloxacin and Ciprofloxacin RS, both dried previously, add 2 mL of a mix-ture of water and phosphoric acid (13:1), add the mobile phase to make exactly 50 mL, and use these solutions as the sample solution and the standard solution, respectively. Per-form the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions, and de-termine the peak areas, AT and AS, of ciprofloxacin in each solution. stand this plate in the vapor of ammonia for 15 minutes, de-velop the plate with a mixture of methanol, dichlorometh-ane, ammonia solution (28) and acetonitrile (4:4:2:1) to a Amount (mg) of ciprofloxacin (C ＝ MS × AT/AS 17H18FN3O3) distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot obtained from the sample solution, corresponding to the spot obtained from the standard solution, is not more in-tense than that obtained from the standard solution. Related substances—Conduct this procedure using light-resistant vessels. To 25 mg of Ciprofloxacin add 2 mL of a mixture of water and phosphoric acid (13:1), then add the mobile phase to make 50 mL, and use this solution as the sample solution. Pipet 2 mL of the sample solution, add the mobile phase to make exactly 20 mL. Pipet 1 mL of this so-lution, add the mobile phase to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 50 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions. Determine each peak area by the automatic integration method: the area of the peak other than ciprofloxacin obtained from the sample so-lution is not larger than the peak area of ciprofloxacin from the standard solution, and the total area of the peaks other than ciproflo…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

cisplatin
type: ChemicalDrugMonograph
pref label:
  en: Cisplatin
  ja: シスプラチン
monograph id: JP18-cisplatin
publisher: JP
status: Official
version: 18
molecular formula: Cl2H6N2Pt
molecular weight: 300.05
definition:
  en: Cisplatin, when dried, contains not less than 98.
appearance:
  en: Cisplatin occurs as a yellow crystalline pow-der. It is sparingly soluble in N,N-dimethylformamide, slightly soluble in water, and practically insoluble in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Cisplatin (1 in 2000) add 2 to 3 drops of a solution of tin (II) chloride dihy-drate (1 in 100): a brown precipitate is formed. (2) Determine the absorption spectrum of a solution of Cisplatin in a solution of sodium chloride in 0.01 mol/L hy- Qualitative Tests <1.09> (1) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Ammonium amminetrichloroplatinate—Conduct this procedure using light-resistant vessels. Dissolve 50 mg of Cisplatin in a solution of sodium chloride (9 in 1000) to make exactly 100 mL, and use this solution as the sample solution. Separately, dissolve 10 mg of ammonium am-minetrichloroplatinate for liquid chromatography, previ-ously dried at 809C for 3 hours, in the solution of sodium chloride (9 in 1000) to make exactly 200 mL. Pipet 2 mL of this solution, add the solution of sodium chloride (9 in 1000) to make exactly 20 mL, and use this solution as the standard solution. Perform the test with exactly 40 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine the peak area of ammonium am-minetrichloroplatinate by the automatic integration method: the peak area obtained from the sample solution is not larger than that from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 209 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with silica gel for liquid chromatography having quaternary ammonium groups (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A solution of ammonium sulfate (1 in 800). Flow rate: Adjust so that the retention time of ammonium amminetrichloroplatinate is about 8 minutes. System suitability— System performance: When the procedure is run with 40 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of ammonium amminetrichloroplatinate are not less than 1500 and not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 40 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of ammonium amminetrichloroplatinate is not more tha…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Conduct this procedure using light-resistant vessels. Weigh accurately about 25 mg each of Cisplatin and Cisplatin RS, previously dried, dissolve in N,N-dimethylfor-mamide to make exactly 25 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly 40 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of cisplatin in each solution. drochloric acid TS (9 in 1000) (1 in 2000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare Amount (mg) of cisplatin (Cl2H6N2Pt) ＝ M S × AT/AS ‌JP XVIII Official Monographs / Citicoline 767 MS: Amount (mg) of Cisplatin RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 310 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with aminopropylsilanized silica gel for liquid chromatography (5 mm in particle diame-ter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of ethyl acetate, methanol, water and N,N-dimethylformamide (25:16:5:5). Flow rate: Adjust so that the retention time of cisplatin is about 4 minutes. System suitability— System performance: When the procedure is run with 40 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of cisplatin are not less than 3000 and not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 40 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of cisplatin is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

citicoline
type: ChemicalDrugMonograph
pref label:
  en: Citicoline
  ja: シチコリン
monograph id: JP18-citicoline
publisher: JP
status: Official
version: 18
molecular formula: C14H26N4O11P2
molecular weight: 488.32
cas number: 987-78-0
definition:
  en: Citicoline contains not less than 98.
appearance:
  en: Citicoline occurs as a white crystalline powder. It is very soluble in water, and practically insoluble in ethanol (99.5). It dissolves in 0.01 mol/L hydrochloric acid TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Citicoline in 0.01 mol/L hydrochloric acid TS (3 in 200,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of a solution of Citicoline RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Citicoline as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Citicoline RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. Amount (z) of free phosphoric acid (H3PO4) ＝ 1/M × AT/AS × 10.32 M: Amount (mg) of Citicoline taken, calculated on the dried basis Related substances—Dissolve 0.10 g of Citicoline in water to make 100 mL, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the area of the peaks other than citicoline obtained from the sample solution is not larger than 3/5 times the peak area of citicolins from the standard solution, and the total area of the peaks other than citicoline from the sample solution is not larger than the peak area of citicoline from the standard solution. For the area of the peaks, hav-ing the relative retention times of about 0.62, about 0.64 and about 1.3 to citicoline, multiply the correction factors, 1.2, 0.7 and 0.5, respectively. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time …
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Citicoline in 8 mL of water: the solution is clear and col-orless. Heavy metals <1.07>—Proceed with 2.0 g of Citico- line according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Citicoline according to Method 4, and perform the test (not more than 2 ppm). Free phosphoric acid—Weigh accurately about 0.1 g of Citicoline, dissolve in water to make exactly 10 mL, and use this solution as the sample solution. Separately, pipet 4 mL of Standard Phosphoric Acid Solution, add water to make exactly 10 mL, and use this solution as the standard solution. To each of the sample solution and the standard solution, add exactly 1 mL of hexaammonium heptamolyb-date-sulfuric acid TS and exactly 0.5 mL of 1-amino-2-naphthol-4-sulfonic acid TS, and after shaking, allow to stand for 30 minutes at 20 ± 19C. To exactly 2 mL each of these solutions add water to make exactly 10 mL, and deter-mine the absorbances, AT and AS, of the solutions obtained from the sample solution and the standard solution at 730 nm as directed under Ultraviolet-visible Spectrometry <2.24>, using the solution, obtained by proceeding with 10 mL of water in the same manner as the sample solution, as the blank. The amount of free phosphoric acid is not more than 0.1z. C14H26N4O11P2: 488.32 P?-[2-(Trimethylammonio)ethyl] cytidine 5?-(monohydrogen diphosphate) [987-78-0] Citicoline contains not less than 98.0z and not more than 102.0z of citicoline (C14H26N4O11P2), cal-culated on the dried basis. Description Citicoline occurs as a white crystalline powder. It is very soluble in water, and practically insoluble in ethanol (99.5). It dissolves in 0.01 mol/L hydrochloric acid TS. Identification (1) Determine the absorption spectrum of a solution of Citicoline in 0.01 mol/L hydrochloric acid TS (3 in 200,000) as directed under Ultraviolet-…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of Citicoline, and dis-solve in water to make exactly 100 mL. Pipet 1 mL of this solution, add water to make exactly 100 mL, and use this so-lution as the sample solution. Separately, weigh accurately about 25 mg of Citicoline RS (separately determine the loss on drying <2.41> under the same conditions as Citicoline), and dissolve in water to make exactly 25 mL. Pipet 1 mL of this solution, add water to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and determine the peak areas, AT and AS, of citicoline in each solution. Amount (mg) of citicoline (C14H26N4O11P2) ＝ MS × AT/AS × 4 MS: Amount (mg) of Citicoline RS taken, calculated on the dried basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: Combine 2 stainless steel columns (4 mm in in-side diameter and 25 cm in length) packed with strongly bas-ic ion exchange resin for liquid chromatography (10 mm in particle diameter) in series. Column temperature: A constant temperature of about 309C. Mobile phase: Dissolve 8.17 g of potassium dihydrogen phosphate in water to make 1000 mL. Adjust the pH of this solution to 3.5 with phosphoric acid. Flow rate: Adjust so that the retention time of citicoline is about 26 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of citicoline are not less than 2000 and 0.9 to 1.6, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of citicoline is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

citri-unshiu-pericarpium
type: ChemicalDrugMonograph
pref label:
  en: Citri Unshiu Pericarpium
  ja: チンピ
monograph id: JP18-citri-unshiu-pericarpium
publisher: JP
status: Official
version: 18
appearance:
  en: Irregular pieces of pericarp, about 2 mm in thickness; externally yellow-red to dark yellow-brown, with numerous small dents associated with oil sacs; internally white to light grayish yellow-brown; light and brittle in texture. Odor, characteristic aroma; taste, bitter and slightly pun-gent.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 0.5 g of pulverized Citrus Unshiu Peel add 10 mL of methanol, warm on a water bath for 2 minutes, and filter. To 5 mL of the filtrate add 0.1 g of mag-nesium in ribbon-form and 1 mL of hydrochloric acid, and allow to stand: a red-purple color develops.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Total BHC's and total DDT's <5.01>—Not more than 0.2 ppm, respectively. Loss on drying <5.01> Not more than 13.0z (6 hours). Total ash <5.01> Not more than 4.0z. Extract content <5.01> Dilute ethanol-soluble extract: not less than 30.0z. Essential oil content <5.01> Perform the test with 50.0 g of pulverized Citrus Unshiu Peel provided that 1 mL of silicon resin is previously added to the sample in the flask: the volume of essential oil is not less than 0.2 mL.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of pulverized Citrus Unshiu Peel, add 30 mL of methanol, heat under a reflux condenser for 15 minutes, centrifuge after cooling, and sepa-rate the supernatant liquid. To the residue add 20 mL of methanol, and proceed in the same manner. Combine the ex-tracts, and add methanol to make exactly 50 mL. Pipet 5 mL of this solution, add water to make exactly 10 mL, and use this solution as the sample solution. Separately, weigh accu-rately about 10 mg of hesperidin for assay, previously dried in a desiccator (silica gel) for not less than 24 hours, and dis-solve in methanol to make exactly 100 mL. Pipet 5 mL of this solution, add water to make exactly 10 mL, and use this solution as the standard solution. Perform the test with ex-actly 10 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and determine the peak areas, AT and AS, of hesperidin in each solution. Amount (mg) of hesperidin ＝ MS × AT/AS × 1/2 MS: Amount (mg) of hesperidin for assay taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 285 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of water, acetonitrile and acetic acid (100) (82:18:1). Flow rate: 1.0 mL per minute (the retention time of hesperidin is about 15 minutes). System suitability— System performance: Dissolve 1 mg each of hesperidin for assay and naringin for thin-layer chromatography in 10 mL of methanol, and add water to make 20 mL. When the procedure is run with 10 mL of this solution under the above operating conditions, naringin and hesperidin are eluted in this order with the resolution between these peaks being not less than 1.5. System repeatability: When the test is repeated…
storage conditions:
  en: Containers—Well-closed contain-ers.

citric-acid-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Citric Acid Hydrate
  ja: クエン酸水和物
monograph id: JP18-citric-acid-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C6H8O7.H2O
molecular weight: 210.14
definition:
  en: Citric Acid Hydrate contains not less than 99.
appearance:
  en: Citric Acid Hydrate occurs as colorless crys-tals, white granules or crystalline powder. It is very soluble in water, and freely soluble in ethanol (99.5). It is efflorescent in dry air.◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Citric Acid Hydrate, previously dried at 1059C for 2 hours, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 2.0 g of Citric Acid Hydrate in water to make 10 mL: the solution is clear and colorless or has no more color than the following control solutions (1), (2) or (3). Control solution (1): To 1.5 mL of Cobalt (II) Chloride CS and 6.0 mL of Iron (III) Chloride CS add diluted dilute hydrochloric acid (1 in 10) to make 1000 mL. Control solution (2): To 2.5 mL of Cobalt (II) Chloride CS, 6.0 mL of Iron (III) Chloride CS and 1.0 mL of Copper (II) Sulfate CS add diluted dilute hydrochloric acid (1 in 10) to make 1000 mL. Control solution (3): To 0.15 mL of Cobalt (II) Chloride CS, 7.2 mL of Iron (III) Chloride CS and 0.15 mL of Cop-per (II) Sulfate CS add diluted dilute hydrochloric acid (1 in 10) to make 1000 mL. Sulfates—Dissolve 2.0 g of Citric Acid Hydrate in water to make 30 mL, and use this solution as the sample so-lution. Separately, dissolve 0.181 g of potassium sulfate in diluted ethanol (3 in 10) to make exactly 500 mL. Pipet 5 mL of this solution, and add diluted ethanol (3 in 10) to make exactly 100 mL. To 4.5 mL of this solution add 3 mL of a so-lution of barium chloride dihydrate (1 in 4), shake, and allow to stand for 1 minute. To 2.5 mL of this solution add 15 mL of the sample solution and 0.5 mL of acetic acid (31), and allow to stand for 5 minutes: the solution has no more turbidity than the following control solution. (not more than 150 ppm). Control solution: Dissolve 0.181 g of potassium sulfate in water to make exactly 500 mL. Pipet 5 mL of this solution, add water to make exactly 100 mL, and proceed in the same manner as above using this solution instead of the sample so-lution. Oxalic acid—Dissolve 0.80 g of Citric Acid Hydrate in 4 mL of water, add 3 mL of hydrochloric acid and 1 g of zinc, and boil for 1 minute. After allowing to stand for 2 minutes, take the supernatant liquid, add 0.25 mL of a solu-tion of phenylhydrazinium chloride (1 in 100), heat to boil, and then cool quickly. To this solution add th…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.55 g of Citric Acid Hy-drate, dissolve in 50 mL of water, and titrate <2.50> with 1 mol/L sodium hydroxide VS (indicator: 1 drop of phenol-phthalein TS). Each mL of 1 mol/L sodium hydroxide VS ＝ 64.04 mg of C6H8O7 ◆Containers and storage Containers—Tight containers.◆ Clarithromycin
type: PharmacopoeiaMonograph

clarithromycin
type: ChemicalDrugMonograph
pref label:
  en: Clarithromycin
  ja: クラリスロマイシン
monograph id: JP18-clarithromycin
publisher: JP
status: Official
version: 18
molecular formula: C38H69NO13
molecular weight: 747.95
definition:
  en: Clarithromycin is a derivative of erythromycin. It contains not less than 950 mg (potency) and not more than 1050 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Clarithromycin occurs as a white crystalline powder and has a bitter taste. It is soluble in acetone and in chloroform, slightly soluble in methanol and in ethanol (95), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mg of Clarithromycin add 2 mL of sulfuric acid, and shake gently: a red-brown color develops. Dissolve 3 mg of Clarithromycin in 2 mL of acetone, and add 2 mL of hydrochloric acid: an orange color develops and changes immediately to red to deep purple. Determine the infrared absorption spectra of Clarithromycin and Clarithromycin RS as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare these spectra: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －96 – －1069(0.25 g calcu-lated on the anhydrous basis, acetone, 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Clarithromycin according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Weigh accurately about 0.1 g of Clarithromycin, dissolve in the mobile phase to make exactly 20 mL, and use this solution as the sample solution. Sepa-rately, weigh accurately about 10 mg of Clarithromycin RS, dissolve in the mobile phase to make exactly 20 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and determine the each peak area by the automatic integration method: the amount of each related substance calculated on the anhydrous basis is not more than 2.0z, and the total amount of them is not more than 5.0z. For these calculations, exclude any peak with an area of less than 0.05z. Amount (z) of each related substance calculated on the anhydrous basis ＝ MS/MT × AT/AS × 100 Total amount (z) of the related substances calculated on the anhydrous basis ＝ MS/MT × SAT/AS × 100 MS: Amount (mg) of Clarithromycin RS taken MT: Amount (mg) of Clarithromycin taken, calculated on the anhydrous basis AS: Peak area of clarithromycin obtained with the stand-ard solution AT: Peak area of each related substance obtained with the sample solution SAT: Total area of the peaks other than clarithromycin obtained with the sample solution Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 5 times as long as the retention time of the main peak, beginning from 2 minutes after injection of the sample solution. System suitability— Test for required detectability: To exactly 2 mL of the standard solution add the mobile phase to make exactly 10 mL, and use this solution…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Clarithromycin and Clarithromycin RS, equivalent to about 50 mg (potency), JP XVIII Official Monographs / Clarithromycin for Syrup 771 ‌and dissolve each in the mobile phase to make exactly 10 mL. Pipet 2 mL each of these solutions, add exactly 2 mL of the internal standard solution, add the mobile phase to make 20 mL, and use these solutions as the sample solution and the standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak methanol, ethyl acetate and acetic acid (100) (90:10:1) to a distance of about 15 cm, and air-dry the plate. Spray evenly sulfuric acid on the plate, and heat the plate at 1059C for 10 minutes: the principal spot obtained from the sample solu-tion and the spot from the standard solution show a black-purple color and the same Rf value. Water <2.48> Not more than 3.0z (0.5 g, volumetric titra-tion, direct titration). area of clarithromycin to that of the internal standard. Amount [mg (potency)] of clarithromycin (C ＝ MS × QT/QS × 1000 38H69NO13) Uniformity of dosage units <6.02> Perform the test accord-ing to the following method: Clarithromycin for Syrup in single-dose packages meet the requirement of the Content MS: Amount [mg (potency)] of Clarithromycin RS taken Internal standard solution—A solution of butyl parahy-droxybenzoate in the mobile phase (1 in 20,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm). Column: A stainless steel column 4 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 509C. Mobile phase: A mixture of diluted 0.2 mol/L potassium dihydrogen phosphate TS (1 in 3) and acetonitrile (13:7). Flow rate: Adjust so that the retention time o…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

clebopride-malate
type: ChemicalDrugMonograph
pref label:
  en: Clebopride Malate
  ja: クレボプリドリンゴ酸塩
monograph id: JP18-clebopride-malate
publisher: JP
status: Official
version: 18
molecular formula: C20H24ClN3O2.C4H6O5
molecular weight: 507.96
definition:
  en: Clebopride Malate, when dried, contains not less than 98.
appearance:
  en: Clebopride Malate occurs as a white crystalline powder. It is freely soluble in acetic acid (100), soluble in methanol, sparingly soluble in water, and slightly soluble in ethanol (99.5). A solution of Clebopride Malate in methanol (1 in 25) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Clebopride Malate in methanol (1 in 80000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, Amount [mg (potency)] of clarithromycin (C38 ＝ MS × QT/QS × 1/5 H69NO13) and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. MS: Amount [mg (potency)] of Clarithromycin RS taken Internal standard solution (1)—A solution of butyl parahy-droxybenzoate in the mobile phase (1 in 1000). Internal standard solution (2)—To exactly 1 mL of the inter-nal standard solution (1) add the mobile phase to make exactly 20 mL. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 509C. Mobile phase: A mixture of diluted 0.2 mol/L potassium Determine the infrared absorption spectrum of Cle-bopride Malate, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers. Perform the test with Clebopride Malate under Flame Coloration Test <1.04> (2): a green color appears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Dissolve 1.0 g of Clebopride Malate in 20 mL of acetic acid (100), add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.25 mL of 0.01 mol/L hydrochloric acid VS by adding 20 mL of acetic acid (100), 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.009z). ‌774 Heavy metals <1.07>—Proceed with 2.0 g of Cle-bopride Malate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 0.10 g of Clebopride Malate in 10 mL of the mobile phase, and use this solution as the sample solution. Pipet 0.2 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the total area of the peaks other than clebopride obtained from the sample solution is not larger than the peak area of clebopride from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 240 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (7 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 3.85 g of ammonium acetate in water to make 500 mL, and filter through a membrane filter with a pore size not exceeding 0.5 mm. To 400 mL of the fil-trate add 600 mL of methanol. Flow rate: Adjust so that the retention time of clebopride is about 15 minutes. Time span of measurement: About 2 times as long as the retention time of clebopride. System suitability— Test for required …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Clebopride Malate, previously dried, dissolve in 30 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 50.80 mg of C20H24ClN3O2.C4H6O5
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

clemastine-fumarate
type: ChemicalDrugMonograph
pref label:
  en: Clemastine Fumarate
  ja: クレマスチンフマル酸塩
monograph id: JP18-clemastine-fumarate
publisher: JP
status: Official
version: 18
molecular formula: C21H26ClNO.C4H4O4
molecular weight: 459.96
definition:
  en: Clemastine Fumarate, when dried, contains not less than 98.
appearance:
  en: Clemastine Fumarate occurs as a white, crys-talline powder. It is odorless. It is sparingly soluble in methanol and in acetic acid (100), slightly soluble in ethanol (95), very slightly soluble in diethyl ether, and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mg of Clemastine Fumarate add 5 mL of sulfuric acid, and shake to dissolve: a yellow color de-velops. Slowly drop this solution into 10 mL of water: the yellow color immediately disappears. To 0.01 g of Clemastine Fumarate add 1 mL of fum-ing nitric acid, and evaporate on a water bath to dryness. Then add 2 mL of diluted hydrochloric acid (1 in 2) and 0.2 g of zinc powder, heat for 10 minutes on a water bath, cool, and filter. Add 20 mL of water to the filtrate. The solu-tion responds to Qualitative Tests <1.09> for primary aro-matic amines. To 5 mL of a solution of Clemastine Fumarate (1 in 50,000), add 5 mL of 4-dimethylaminobenzaldehyde TS, and warm for 10 minutes: a red-purple color develops. Perform the test with Clemastine Fumarate as di-rected under Flame Coloration Test <1.04> (2): a green color appears. Dissolve 0.04 g of Clemastine Fumarate and 0.01 g of fumaric acid for thin-layer chromatography in 2 mL each of a mixture of ethanol (95) and water (4:1) by gentle warming, and use these solutions as the sample solution and the stand-ard solution, respectively. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of isopropyl ether, formic acid and water (90:7:3) to a distance of about 10 cm, and air-dry the plate. Examine the plate under ultraviolet light (main wavelength: 254 nm): the spot with larger Rf value from the sample solution has the same Rf value as the spot from the standard solution. D Optical rotation <2.49> [a]20: ＋16 – ＋189(after drying, 0.1 g, methanol, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Clemastine Fumarate in 10 mL of methanol by warming: the solution is clear and colorless. Heavy metals <1.07>—Perform the test with 1.0 g of Clemastine Fumarate according to Method 2. Prepare the control solution with 2.0 mL of Standard Lead Solution (not ‌JP XVIII Official Monographs / Clindamycin Hydrochloride 775 more than 20 ppm). Arsenic <1.11>—Take 1.0 g of Clemastine Fumarate, prepare the test solution according to Method 3, and per-form the test (not more than 2 ppm). Related Substances—Dissolve 0.10 g of Clemastine Fumarate in 5 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 250 mL, and use this solution as the standard solution (1). Pipet 5 mL of the standard solu-tion (1), add methanol to make exactly 10 mL, and use this solution as the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 5 mL each of the sample solution and stand-ard solutions (1) and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chlo-roform, methanol and ammonia solution (28) (90:10:1) to a distance of about 15 cm, and air-dry the plate. After spraying evenly Dragendorff 's TS on the plate, immediately spray evenly hydrogen peroxide TS: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution (1), and not more than 2 spots from the sample solution are more intense than the spot from the standard solution (2). Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Clemastine Fumarate, previously dried, dissolved in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS soluble in ethanol (99.5). Identification (1) Determine the infrared absorption spec-trum of Clindamycin Hydrochloride as directed in the potas-sium chloride disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Clindamycin Hydrochloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers. (2) A solution of Clindamycin Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> (2) for chloride. D Optical rotation <2.49> [a]25: ＋135 – ＋1509(0.5 g calcu-lated on the anhydrous basis, water, 25 mL, 100 mm). Purity (1) Heavy metals <1.07>—Proceed with 2.0 g of Clindamycin Hydrochloride according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Use the sample solution ob-tained in the Assay as the sample solution. Pipet 1 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the peak area of clindamycin B, having the relative retention time of about 0.7 to clindamycin, and that of 7-epiclindamy-cin, having the relative retention time of about 0.8, obtained from the sample solution are not larger than 2 times the peak area of clindamycin from the standard solution, the area of the peak other than clindamycin and the peaks mentioned above from the sample soluti…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

clindamycin-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Clindamycin Hydrochloride
  ja: クリンダマイシン塩酸塩
monograph id: JP18-clindamycin-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C18H33ClN2O5S.HCl
molecular weight: 461.44
cas number: 21462-39-5
definition:
  en: Clindamycin Hydrochloride is the hydrochloride of a derivative of lincomycin. It contains not less than 838 mg (potency) and not more than 940 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Clindamycin Hydrochloride occurs as white to grayish white, crystals or crystalline powder. It is freely soluble in water and in methanol, and slightly damycin from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 2 times as long as the retention time of clindamycin, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 1 mL of the standard solution, and add the mobile phase to make exactly 10 mL. Confirm that the peak area of clindamycin obtained with 20 mL of this solution is equivalent to 7 to 13z of that with 20 mL of the standard solution. System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of clindamycin are not less than 6000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of clindamycin is not more than 2.0z. Water <2.48> Not more than 6.0z (0.3 g, volumetric titra-tion, direct titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Clindamycin Hydro-chloride and Clindamycin Hydrochloride RS, equivalent to about 20 mg (potency), dissolve each in the mobile phase to make exactly 20 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the ‌776 test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of clindamycin in each solution. Uniformity of dosage units <6.02> Perform the test accord-ing to the following method: it meets the requirement of the Content uniformity test. To 1 capsule of Clindamycin Hydrochloride Capsules add Amount [mg (potency)] of clindamycin (C ＝ MS × AT/AS × 1000 18H33ClN2O5S) a suitable amount of the mobile phase, shake for 30 minutes, and add the mobile phase to make exactly V mL so that each mL contains 0.75 mg (potency) of Clindamycin Hydrochlo- MS: Amount [mg (potency)] of Clindamycin Hydrochlo-ride RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 25 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: To 0.05 mol/L potassium dihydrogen phos-phate TS add 8 mol/L potassium hydroxide TS to adjust the pH to 7.5. To 550 mL of this solution add 450 mL of aceto-nitrile for liquid chromatography. Flow rate: Adjust so that the retention time of clindamy-cin is about 10 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of clindamycin are not less than 6000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 2…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

clindamycin-phosphate
type: ChemicalDrugMonograph
pref label:
  en: Clindamycin Phosphate
  ja: クリンダマイシンリン酸エステル
monograph id: JP18-clindamycin-phosphate
publisher: JP
status: Official
version: 18
molecular formula: C18H34ClN2O8PS
molecular weight: 504.96
definition:
  en: Clindamycin Phosphate is a derivative of clindamy- ＝ MS × AT/AS 18 33 2 5 cin. It contains not less than 800 mg (potency) and not MS: Amount [mg (potency)] of Clindamycin Hydrochlo-ride RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm).
appearance:
  en: Clindamycin Phosphate occurs as a white to pale yellow-white crystalline powder. It is freely soluble in water, sparingly soluble in methanol, and practically insoluble in ethanol (95).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Clindamycin Phosphate, previously dried at 1009C for 2 hours, as directed in the paste method under Infrared Spec-trophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Clindamycin Phos-phate RS previously dried at 1009C for 2 hours: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋115 – ＋1309(0.25 g calcu-lated on the anhydrous basis, water, 25 mL, 100 mm). pH <2.54> Dissolve 0.10 g of Clindamycin Phosphate in 10 mL of water. The pH of the solution is between 3.5 and 4.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Clindamycin Phosphate in 10 mL of freshly boiled and cooled water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g of Clin- damycin Phosphate according to Method 4, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 5 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Clindamycin Phosphate according to Method 4, and per-form the test (not more than 2 ppm). Related substances—Dissolve 0.1 g of Clindamycin Phosphate in 100 mL of the mobile phase, and use this solu-tion as the sample solution. Pipet 1 mL of the sample solu-tion, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and determine each peak area by the automatic integration method: the peak area of clindamycin, having the relative retention time of about 1.8 to clindamycin phosphate, obtained from the sam-ple solution is not larger than 1/2 times the peak area of clin-damycin phosphate from the standard solution, and the total ‌778 area of the peaks other than clindamycin phosphate from the sample solution is not larger than 4 times the peak area of clindamycin phosphate from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 2 times as long as the retention time of clindamycin phosphate, beginning after the solvent peak. System suitability— System performance, and system repeatability: Proceed as directed in the system suitability in the Assay. Test for required detectability: Measure exactly 1 mL of the standard solution, and add the mobile phase to make ex-actly 10 mL. Confirm that the peak area of c…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Clindamycin Phos-phate and Clindamycin Phosphate RS, equivalent to about 20 mg (potency), add exactly 25 mL of the internal standard solution and the mobile phase to make 100 mL, and use these solutions as the sample solution and standard solution. Perform the test with 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of clindamycin phos-phate to that of the internal standard. Amount [ mg (potency)] of clindamycin (C18H33ClN2O5S) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Clindamycin Phosphate RS taken Internal standard solution—A solution of methyl parahy-droxybenzoate in the mobile phase (3 in 50,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm). Column: A stainless steel column 4 mm in inside diameter and 25 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 10.54 g of potassium dihydrogen phosphate in 775 mL of water, adjust the pH to 2.5 with phosphoric acid, and add 225 mL of acetonitrile. Flow rate: Adjust so that the retention time of clindamy-cin phosphate is about 8 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, clindamycin phosphate and the internal standard are eluted in this order with the resolution between these peaks being not less than 4. System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of clindamycin phosphate to that of the in-ternal standard is not more than 2.5z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

clinofibrate
type: ChemicalDrugMonograph
pref label:
  en: ‌Clinofibrate
  ja: クリノフィブラート
monograph id: JP18-clinofibrate
publisher: JP
status: Official
version: 18
molecular formula: C28H36O6
molecular weight: 468.58
cas number: 30299-08-2
appearance:
  en: Clinofibrate occurs as a white to yellowish white powder. It is odorless and has no taste. It is freely soluble in methanol, in ethanol (99.5), in ace-tone and in diethyl ether, and practically insoluble in water. A solution of Clinofibrate in methanol (1 in 20) shows no optical rotation. Melting point: about 1469C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Clinofibrate in ethanol (99.5) (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Clinofibrate, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Clinofibrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Clinofibrate according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.10 g of Clinofibrate in 10 mL of acetone, and use this solution as the sample so-lution. Pipet 1 mL of the sample solution, and add acetone to make exactly 50 mL. Pipet 5 mL of this solution, add ace-tone to make exactly 20 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 50 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chlo-roform, cyclohexane and acetic acid (100) (12:5:3) to a dis-tance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solu-tion. Loss on drying <2.41> Not more than 1.0z (1 g, in vacu-um, 609C, 3 hours). Residue on ignition <2.44> Not more than 0.2z (1 g). Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column about 4 mm in inside di-ameter and about 30 cm in length, packed with silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 209C. Mobile phase: A mixture of hexane and 2-propanol (500:3). Flow rate: Adjust so that the retention time of the peak appearing first is about 35 minutes. Selection of column: Proceed with 5 mL of the sample so-lution under the above operating conditions. Use a column giving a complete separation of the three peaks.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.45 g of Clinofibrate, pre-viously dried, dissolve in 40 mL of ethanol (99.5), add 30 mL of water, and titrate <2.50> with 0.1 mol/L sodium hydrox-ide VS (indicator: 3 drops of phenolphthalein TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 23.43 mg of C28H36O6
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

clobetasol-propionate
type: ChemicalDrugMonograph
pref label:
  en: Clobetasol Propionate
  ja: クロベタゾールプロピオン酸エステル
monograph id: JP18-clobetasol-propionate
publisher: JP
status: Official
version: 18
molecular formula: C25H32ClFO5
molecular weight: 466.97
definition:
  en: Clobetasol Propionate, when dried, contains not less than 97.
appearance:
  en: Clobetasol Propionate occurs as a white to pale yellow-white crystalline powder. It is soluble in methanol and in ethanol (99.5), and practi-cally insoluble in water. It gradually turns yellow by light. Melting point: about 1969C (with decomposition). ‌Identification Determine the infrared absorption spectra of Clobetasol Propionate as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare the spec-trum with the Reference Spectrum or the spectrum of Clobetasol Propionate RS: both spectra exhibit similar in-tensities of absorbance at the same wave numbers. D Optical rotation <2.49> [a]20: ＋109 – ＋1159(after drying, 0.1 g, methanol, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Clobetasol Propionate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 10 mg of Clobetasol Propionate in 100 mL of the mobile phase, and use this solu-tion as the sample solution. Pipet 5 mL of the sample solu-tion, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions, and determine each peak area of these solutions by the automatic integration method: the area of the peak other than clobetasol propionate obtained from the sample solution is not larger than 2/5 times the peak area of clobetasol propionate from the standard solution. Furthermore, the total area of the peaks other than clobetasol propionate from the sample so-lution is not larger than the peak area of clobetasol propionate from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 2.5 times as long as the retention time of clobetasol propionate, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 2 mL of the standard solution, and add the mobile phase to make exactly 50 mL. Confirm that the peak area of clobetasol propionate ob-tained with 10 mL of this solution is equivalent to 2.8 to 5.2z of that with 10 mL of the standard solution. System performance: Dissolve 20 mg of Clobetasol Propionate in 20 mL of methanol. To 5 mL of this solution add 10 mL of a solution of beclometasone dipropionate in methanol (1 in 1000), and then add the mobile phase to make 50 mL. When the procedure is run with 10 mL of this solu-tion under the above condition…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 10 mg each of Clobetasol Propionate and Clobetasol Propionate RS, both previously dried, dissolve each in the mobile phase, add exactly 100 mL of the internal standard solution, add the mobile phase to make 250 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of clobetasol propionate to that of the internal stand-ard. Amount (mg) of clobetasol propionate (C25H32ClFO5) ＝ MS × QT/QS MS: Amount (mg) of Clobetasol Propionate RS taken Internal standard solution—A solution of beclometasone dipropionate in the mobile phase (1 in 5000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 240 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 7.80 g of sodium dihydrogen phos-phate dihydrate in 900 mL of water, adjust the pH to 2.5 with phosphoric acid, and then add water to make 1000 mL. To 425 mL of this solution add 475 mL of acetonitrile and 100 mL of methanol. Flow rate: Adjust so that the retention time of clobetasol propionate is about 10 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above conditions, clobetasol propionate and the internal standard are eluted in this order with the resolution between these peaks being not less than 8. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above condi-tions, the relative standard deviation of the ratio of the peak area of clobetasol propionate to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

clocapramine-hydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Clocapramine Hydrochloride Hydrate
  ja: クロカプラミン塩酸塩水和物
monograph id: JP18-clocapramine-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C28H37ClN4O.2HCl.H2O
molecular weight: 572.01
cas number: 60789-62-0
definition:
  en: Clocapramine Hydrochloride Hydrate, when dried, contains not less than 98.
appearance:
  en: Clocapramine Hydrochloride Hydrate occurs as white, crystals or crystalline powder. It is odorless, and has a bitter taste. It is freely soluble in acetic acid (100), sparingly soluble in water and in methanol, slightly soluble in ethanol (95), in chloroform and in isopropylamine, and practically insoluble in acetic anhydride and in diethyl ether. It is gradually colored by light. Melting point: about 2609C (with decomposition, after drying).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Clocapramine Hydrochloride Hydrate (1 in 2500) add 1 mL of nitric acid: a blue color develops at first, and rapidly changes to deep blue, and then changes to green to yellow-green. Determine the absorption spectrum of a solution of Clocapramine Hydrochloride Hydrate in methanol (1 in 40,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Clocapramine Hydrochloride Hydrate as directed in the po-tassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolve 0.1 g of Clocapramine Hydrochloride Hy-drate in 10 mL of water by warming, and after cooling, add 2 mL of ammonia TS, and filter. Acidify the filtrate with dilute nitric acid: the solution responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfate <1.14>—Dissolve 0.5 g of Clocapra-mine Hydrochloride Hydrate in 40 mL of water by warming, after cooling, and add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.048z). Heavy metals <1.07>—Proceed with 2.0 g of Clocapramine Hydrochloride Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 0.10 g of Clocapramine Hydrochloride Hydrate in 10 mL of a mixture of chloroform and isopropylamine (99:1), and use this solution as the sample solution. Pipet 1 mL of the sam-ple solution, add a mixture of chloroform and isopropyla-mine (99:1) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of diethyl ether, ethyl acetate, methanol and ammonia solution (28) (100:70:40:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> 2.0 – 3.5z (0.5 g, in vacuum at a pressure not exceeding 0.67 kPa, phosphorus (V) oxide, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Clocapramine Hy-drochloride Hydrate, previously dried, dissolve in 70 mL of a mixture of acetic anhydride and acetic acid (100) (6:1), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 27.70 mg of C28H37ClN4O.2HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

clofedanol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Clofedanol Hydrochloride
  ja: クロフェダノール塩酸塩
monograph id: JP18-clofedanol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C17H20ClNO.HCl
molecular weight: 326.26
cas number: 511-13-7
definition:
  en: Clofedanol Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Clofedanol Hydrochloride occurs as white, crystals or crystalline powder. It is freely soluble in methanol, in ethanol (95) and in acetic acid (100), sparingly soluble in water, and practically insoluble in diethyl ether. A solution of Clofedanol Hydrochloride in methanol (1 in 20) does not show optical rotation. Melting point: about 1909C (after drying, with decompo-sition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Clofedanol Hydrochloride in 0.01 mol/L hydro-chloric acid TS (1 in 2500) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Clofedanol Hydrochloride, previously dried, as directed in the potassium bromide disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Clofedanol Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Clofedanol Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 0.05 g of Clofedanol Hydrochloride in 25 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 3 mL ‌782 each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area of both solu-tions by the automatic integration method: the total area of the peaks other than clofedanol obtained from the sample solution is not larger than the peak area of clofedanol from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 220 nm). Column: A stainless steel column about 4 mm in inside diameter and about 15 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 1.34 g of potassium methanesul-fonate in diluted phosphoric acid (1 in 1000) to make 1000 mL, and to 650 mL of this solution add 350 mL of metha-nol. Flow rate: Adjust so that the retention time of clofedanol is about 9 minutes. Selection of column: Dissolve 0.01 g each of Clofedanol Hydrochloride and ethyl parahydroxybenzoate in methanol to make 100 mL. Proceed with 3 mL of this solution under the above operating conditions, and calculate the resolution. Use a column giving elution of clofedanol and ethyl parahy-droxybenzoate in this order with the resolution of these peaks being not less than 4. Detection sensitivity: Adjust the detection sensitivity so that the peak height of clofedanol obtained from 3 mL of the standard solution composes betwee…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Clofedanol Hydro-chloride, previously dried, dissolve in 15 mL of acetic acid (100), add 35 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS basis. Description Clofibrate occurs as a colorless or light yellow, clear, oily liquid. It has a characteristic odor and taste, which is bitter at first, and subsequently sweet. It is miscible with methanol, with ethanol (95), with ethanol (99.5), with diethyl ether and with hexane, and prac-tically insoluble in water. It is gradually decomposed by light. Identification (1) Determine the absorption spectrum of a solution of Clofibrate in ethanol (99.5) (1 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum 1 or the spectrum of a solution of Clofibrate RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Separately, determine the absorption spectrum of a solution of Clofibrate in ethanol (99.5) (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum 2 or the spectrum of a solution of Clofibrate RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Clofibrate as directed in the liquid film method under In-frared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Clofibrate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. D Refractive index <2.45> n20: 1.500 – 1.505 Specific gravity <2.56> d 20: 1.137 – 1.144 Purity (1) Acidity—Dissolve 2.0 g of Clofibrate in 100 mL of neutralized…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

clofibrate
type: ChemicalDrugMonograph
pref label:
  en: Clofibrate
  ja: クロフィブラート
monograph id: JP18-clofibrate
publisher: JP
status: Official
version: 18
molecular formula: C12H15ClO3
molecular weight: 242.7
definition:
  en: Clofibrate contains not less than 98.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Clofibrate, add exactly 50 mL of 0.1 mol/L potassium hydroxide-ethanol VS, and heat in a water bath under a reflux condenser with a carbon dioxide absorbing tube (soda-lime) for 2 hours with frequent shaking. Cool, and titrate <2.50> immediately the excess potassium hydroxide with 0.1 mol/L hydrochloric acid VS (indicator: 3 drops of phenolphthalein TS). Perform a blank determination in the same manner. Each mL of 0.1 mol/L potassium hydroxide-ethanol VS ＝ 24.27 mg of C12H15ClO3
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

clomifene-citrate
type: ChemicalDrugMonograph
pref label:
  en: Clomifene Citrate
  ja: クロミフェンクエン酸塩
monograph id: JP18-clomifene-citrate
publisher: JP
status: Official
version: 18
molecular formula: C26H28ClNO.C6H8O7
molecular weight: 598.08
cas number: 50-41-9
definition:
  en: Clomifene Citrate, when dried, contains not less than 98.
appearance:
  en: Clomifene Citrate occurs as a white to pale yel-low-white powder. It is odorless. It is freely soluble in methanol and in acetic acid (100), sparingly soluble in ethanol (95), and practically insoluble in diethyl ether. It gradually changes in color by light. Melting point: about 1159C
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 2 mL of a solution of Clomifene Citrate in methanol (1 in 200) add 2 mL of Reinecke salt TS: a light red precipitate is produced. Determine the absorption spectrum of a solution of Clomifene Citrate in 0.1 mol/L hydrochloric acid TS (1 in 50,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of a solution of Clomifene Citrate RS prepared in the same manner as the sample solu-tion: both spectra exhibit similar intensities of absorption at the same wavelengths. A solution of Clomifene Citrate in methanol (1 in 200) responds to Qualitative Tests <1.09> (1) and (2) for ci-trate salt.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—A solution of 1.0 g of Clomifene Citrate in 30 mL of methanol is clear and colorless. (2) Heavy metals <1.07>—Proceed with 2.0 g of Clomi- fene Citrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Loss on drying <2.41> Not more than 1.0z (1 g, in vacu-um, phosphorus (V) oxide, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g). Isomer ratio To 10 mg of Clomifene Citrate add 10 mL of water and 1 mL of sodium hydroxide TS, and shake to uni-formly disperse. Add 10 mL of ethyl acetate, shake vigor-ously for 5 minutes, allow to stand for 5 minutes, and use the upper layer as the sample solution. Perform the test with 1 mL of the sample solution as directed under Gas Chroma-tography <2.02> according to the following conditions. De-termine the areas of two adjacent peaks, Aa and Ab, having the retention time of about 8 minutes, where Aa is the peak area of shorter retention time and Ab is the peak area of lon-ger retention time: Ab/(Aa ＋ Ab) is between 0.3 and 0.5. Operating conditions— Detector: A hydrogen flame-ionization detector. Column: A fused silica column 0.25 mm in inside diameter and 15 m in length, coated the inside surface with a layer about 0.1 mm thick of dimethylpolysiloxane for gas chroma-tography. Column temperature: A constant temperature of about 2309C. Injection port temperature: A constant temperature of about 2709C. Detector temperature: A constant temperature of about 3009C. Carrier gas: Helium. Flow rate: Adjust so that the retention time of the first peak of clomifene citrate is about 7.5 minutes. Split ratio: 1:50. System suitability— System performance: When the procedure is run with 1 mL of the sample solution under the above operating conditions, the resolution between the two adjacent peaks having the retention time of about 8 minutes is not less than 5. System repeatability: When the test is repeated 6 times …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 1 g of Clomifene Citrate, previously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (indicator: 2 drops of crystal violet TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 59.81 mg of C26H28ClNO.C6H8O7
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

clomipramine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Clomipramine Hydrochloride
  ja: クロミプラミン塩酸塩
monograph id: JP18-clomipramine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C19H23ClN2.HCl
molecular weight: 351.31
definition:
  en: Clomipramine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Clomipramine Hydrochloride occurs as a white to pale yellow, crystalline powder. It is odorless. It is very soluble in acetic acid (100), freely soluble in water, in methanol and in chloroform, soluble in ethanol (95), sparingly soluble in acetic anhydride, slightly soluble in acetone, and practically insoluble in ethyl acetate and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 3 mg of Clomipramine Hydro-chloride in 1 mL of nitric acid: a deep blue color develops. Determine the absorption spectrum of a solution of Clomipramine Hydrochloride in 0.1 mol/L hydrochloric acid TS (3 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi-ties of absorption at the same wavelengths. Take 1 g of Clomipramine Hydrochloride in a sepa-rator, dissolve in 10 mL of water, add 5 mL of sodium hy-droxide TS, and extract with two 30-mL portions of diethyl ether [the water layer is used for Identification (4)]. Combine the diethyl ether extracts, add 20 mL of water, and shake. Take diethyl ether layer, dry with a small portion of anhy-drous sodium sulfate, and filter. Evaporate the combined ex-tracts by warming on a water bath, and proceed the test with the residue as directed under Flame Coloration Test <1.04> (2): a green color appears. The solution neutralized by adding dilute nitric acid to the water layer obtained in (3) responds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Clomipramine Hydrochloride in 10 mL of water: the pH of this solution is between 3.5 and 5.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Clomipramine Hydrochloride in 10 mL of water: the solu-tion is clear and colorless to pale yellow. Heavy metals <1.07>—Proceed with 2.0 g of Clomipramine Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Clomipramine Hydrochloride according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.20 g of Clomipra-mine Hydrochloride in 10 mL of methanol, and use this so- ‌786 lution as the sample solution. Separately, weigh 20 mg of Imipramine Hydrochloride, dissolve in methanol to make exactly 100 mL, and use this solution as the standard solu-tion (1). Then pipet 1 mL of the sample solution, and add methanol to make exactly 50 mL. Pipet 5 mL of the solu-tion, add methanol to make exactly 50 mL, and use this solu-tion as the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solutions (1) and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, acetone and ammonia solution (28) (15:5:1) to a dis-tance of about 10 cm, and air-dry the plate. Spray evenly po-tassium dichromate-sulfuric acid TS on the plate: the spot obtained from the sample solution, corresponding to that from the standard solution (1), is not more intense than the spot from the standard solution (1). Each of the spots other than the principal spot and the spot mentioned above from the sample solution is not more intense than the spot from the standard solution (2). Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Clomipramine Hy-drochloride, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 35.13 mg of C19H23ClN2.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

clonazepam
type: ChemicalDrugMonograph
pref label:
  en: Clonazepam
  ja: クロナゼパム
monograph id: JP18-clonazepam
publisher: JP
status: Official
version: 18
molecular formula: C15H10ClN3O3
molecular weight: 315.71
cas number: 1622-61-3
definition:
  en: Clonazepam, when dried, contains not less than 99.
appearance:
  en: Clonazepam occurs as white to light yellow, crystals or crystalline powder. It is sparingly soluble in acetic anhydride and in acetone, slightly soluble in methanol and in ethanol (95), very slightly soluble in diethyl ether, and practically insoluble in water. It is gradually colored by light. Melting point: about 2409C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Clonazepam in methanol (1 in 100,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Clonazepam, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Clonazepam as directed under Clonazepam Fine Granules
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—To 1.0 g of Clonazepam add 50 mL of water, allow to stand for 1 hour with occasional shaking, and filter. Discard the first 20 mL portion of the fil-trate, take the subsequent 20 mL portion of the filtrate, and add 6 mL of dilute nitric acid and water to make 50 mL. Use this solution as the test solution, and perform the test. Pre-pare the control solution as follows: to 0.25 mL of 0.01 mol/L hydrochloric acid VS add 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.022z). Heavy metals <1.07>—Proceed with 1.0 g of Clonazepam according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.25 g of Clonazepam in 10 mL of acetone, and use this solution as the sample so-lution. Pipet 1 mL of the sample solution, add acetone to make exactly 100 mL, then pipet 1 mL of this solution, add acetone to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of nitromethane and acetone (10:1) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the princi-pal spot obtained from the sample solution are not more in-tense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.30z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Clonazepam, previ-ously dried, dissolve in 70 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 31.57 mg of C15H10ClN3O3
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

clonidine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Clonidine Hydrochloride
  ja: クロニジン塩酸塩
monograph id: JP18-clonidine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C9H9Cl2N3.HCl
molecular weight: 266.55
cas number: 4205-91-8
appearance:
  en: Clonidine Hydrochloride occurs as white, crys-tals or crystalline powder. It is freely soluble in methanol, soluble in water and in ethanol (95), slightly soluble in acetic acid (100), and practi- cally insoluble in acetic anhydride and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Clonidine Hy-drochloride (1 in 1000) add 6 drops of Dragendorff's TS: an orange precipitate is formed. Determine the absorption spectrum of a solution of Clonidine Hydrochloride in 0.01 mol/L hydrochloric acid TS (3 in 10,000) as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Clonidine Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. A solution of Clonidine Hydrochloride (1 in 50) re-sponds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Clonidine Hydrochloride in 20 mL of water: the pH of this solution is between 4.0 and 5.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Clonidine Hydrochloride in 20 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 2.0 g of Cloni- dine Hydrochloride according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 0.5 g of Clonidine Hydrochloride according to Method 3, and per-form the test (not more than 4 ppm). Related substances—Dissolve 0.20 g of Clonidine Hydrochloride in 2 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, and add methanol to make exactly 100 mL. Pipet 1 mL and 2 mL of this solution, to each add methanol to make exactly 20 mL, and use these solutions as the standard solution (1) and the standard solution (2), respectively. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 2 mL each of the sample solution and stand-ard solutions (1) and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of tolu-ene, 1,4-dioxane, ethanol (99.5) and ammonia solution (28) (10:8:2:1) to a distance of about 12 cm, air-dry the plate, and then dry at 1009C for 1 hour. Spray evenly sodium hypochlorite TS on the plate, air-dry the plate for 15 minutes, and then spray evenly potassium iodide starch TS on the plate: the spots other than the principal spot and the spot of the starting point obtained from the sample solution are not more intense than the spot from the standard solu-tion (2), and the numbers of spots other than the principal spot and the spot of the starting point, which are more in-tense than the spot from the standard solution (1), are not more than 3. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Clonidine Hydro-chloride, previously dried, and dissolve in 30 mL of acetic acid (100) by warming. After cooling, add 70 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determina-tion in the same manner, and make any necessary correction. ‌790 Each mL of 0.1 mol/L perchloric acid VS ＝ 26.66 mg of C9H9Cl2N3.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cloperastine-fendizoate
type: ChemicalDrugMonograph
pref label:
  en: Cloperastine Fendizoate
  ja: クロペラスチンフェンジゾ酸塩
monograph id: JP18-cloperastine-fendizoate
publisher: JP
status: Official
version: 18
molecular formula: C20H24ClNO.C20H14O4
molecular weight: 648.19
cas number: 85187-37-7
definition:
  en: Cloperastine Fendizoate, when dried, contains not less than 99.
appearance:
  en: Cloperastine Fendizoate occurs as white, crys-tals or crystalline powder. It is freely soluble in isopropylamine, slightly soluble in methanol, in ethanol (99.5) and in acetic acid (100), and practically insoluble in water. A solution of Cloperastine Fendizoate in isopropylamine (1 in 20) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cloperastine Fendizoate in methanol (3 in 200,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Cloperastine Fendizoate as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—To 2.0 g of Cloperastine Fen-dizoate add 50 mL of water, warm at 709C for 5 minutes, cool, and filter. To 25 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.40 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.014z). Heavy metals <1.07>—Proceed with 1.0 g of Cloper- astine Fendizoate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). 4-Chlorobenzophenone—Dissolve exactly 25 mg of Cloperastine Fendizoate in the mobile phase A to make ex-actly 50 mL, and use this solution as the sample solution. Separately, dissolve exactly 25 mg of 4-chlorobenzophenone in the mobile phase A to make exactly 200 mL. Pipet 1 mL of this solution, add the mobile phase A to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas of 4-chlorobenzophenone by the automatic integration method: the peak area of 4-chlorobenzophenone obtained from the sample solution is not larger than that from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 226 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase A: A mixture of 0.1 mol/L potassium dihy-drogen phosphate TS, acetonitrile for liquid chromatogra-phy and perchloric acid (400:320:1). Mobile phase B: A mixture of acetonitrile for liquid chro-matography, 0.1 mol/L potassium dihydrogen phosphate TS and perchloric acid (1050:450:1). Flowing of mobile phase: Contr…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 1 g of dried Cloperastine Fendizoate, add 100 mL of acetic acid (100), warm to dis-solve, cool, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determina-tion in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 64.82 mg of C20H24ClNO.C20H14O4
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

cloperastine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cloperastine Hydrochloride
  ja: クロペラスチン塩酸塩
monograph id: JP18-cloperastine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C20H24ClNO.HCl
molecular weight: 366.32
cas number: 14984-68-0
definition:
  en: Cloperastine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Cloperastine Hydrochloride occurs as white, crystals or crystalline powder. It is very soluble in water, in methanol, in ethanol (95) and in acetic acid (100), and soluble in acetic anhydride. A solution of Cloperastine Hydrochloride (1 in 10) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cloperastine Hydrochloride in 0.1 mol/L hydro-chloric acid TS (1 in 2500) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum 1: both spectra exhibit similar intensities of absorption at the same wavelengths. Sepa-rately, determine the absorption spectrum of a solution of Cloperastine Hydrochloride in 0.1 mol/L hydrochloric acid TS (1 in 62,500) as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum 2: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cloperastine Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Shake 10 mL of a solution of Cloperastine Hydro-chloride (1 in 100) with 2 mL of ammonia TS and 20 mL of diethyl ether, separate the water layer, wash the water layer with 20 mL of diethyl ether, and filter. Acidify the filtrate with dilute nitric acid: the solution responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Cloperastine Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 40 mg of Cloperastine Hydrochloride in 50 mL of the mobile phase, and use this solution as the sample solution. Pipet 1 mL of the sample so-lution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the area of the peaks, having the relative retention times of about 0.8 and about 3.0 to cloperastine obtained from the sample solu-tion are not larger than the peak area of cloperastine from the standard solution, and the area of the peak having the relative retention time about 2.0 from the sample solution is not larger than 5/3 times the peak area of cloperastine from the standard solution. The area of the peak other than cloperastine and the peaks mentioned above from the sample solution are not larger than 3/5 times the peak area of cloperastine from the standard solution, and the total area of these peaks is not larger than 2 times the peak area of cloperastine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 222 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of methanol, 0.1 mol/L potas-sium dihydrogen phosphate TS and perchloric acid (500:250:1). Flow rate: Adjust so that the retention time of cloper-astine is about 7 minutes. Time span of measurement: About 4 times as long as…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Cloperastine Hy-drochloride, previously dried, dissolve in 70 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 36.63 mg of C20H24ClNO.HCl ‌JP XVIII Official Monographs / Clopidogrel Sulfate 793
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

clopidogrel-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Clopidogrel Sulfate
  ja: クロピドグレル硫酸塩
monograph id: JP18-clopidogrel-sulfate
publisher: JP
status: Official
version: 18
molecular formula: C16H16ClNO2S.H2SO4
molecular weight: 419.9
cas number: 120202-66-6
definition:
  en: Clopidogrel Sulfate contains not less than 97.
appearance:
  en: Clopidogrel Sulfate occurs as a white to pale yellow-white, crystalline powder or powder. It is freely soluble in water and in methanol, and soluble in ethanol (99.5). It gradually develops a brown color on exposure to light. Melting point: about 1779C (with decomposition). 2.5 mL of this solution, add a mixture of acetonitrile for liquid chromatography and the mobile phase A (3:2) to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the area of the peak, having the relative retention time of about 0.5 and about 1.1 to clopidogrel, obtained from the sample solution is not larger than 2 times the peak area of clopidogrel from the standard solution, the area of the peak other than clopidogrel and the peaks men-tioned above from the sample solution is not larger than the peak area of clopidogrel from the standard solution, and the total area of the peaks other than clopidogrel from the sam-ple solution is not larger than 5 times the peak area of clopidogrel from the standard solution. Operating conditions— Detector, column and column temperature: Proceed as di-rected in the operating conditions in the Assay. Mobile phase A: Dissolve 0.87 g of sodium 1-pen-tanesufonate in 1000 mL of water, and adjust to pH 2.5 with phosphoric acid. To 950 mL of this solution add 50 mL of methanol. Mobile phase B: A mixture of acetonitrile for liquid chro-matography and methanol (19:1). Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) solution of Clopidogrel Sulfate in methanol (3 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Clopidogrel Sulfate RS pre-pared in the same manner as the sample solution: both spec-tra exhibit similar intensities of absorption at the same wave-lengths. Determine the infrared absorption spectrum of Clopidogrel Sulfate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Clopidogrel Sulfate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, dissolve Clopidogrel Sulfate, or each of Clopidogrel Sulfate and Clopidogrel Sulfate RS in ethanol (99.5), respectively. Then evaporate the ethanol to dryness, and repeat the test on the residues dried in vacuum. Perform the test with Clopidogrel Sulfate as directed under Flame Coloration Test <1.04> (2): a green color ap-pears. A solution of Clopidogrel Sulfate in a mixture of water and methanol (1:1) (1 in 100) responds to Qualitative Tests <1.09> (1) for sulfate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Clopidogrel Sulfate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 65 mg of Clopidogrel Sulfate in 10 mL of a mixture of acetonitrile for liquid chro-matography and mobile phase A (3:2), and use this solution as the sample solution. Pipet 2 mL of the sample solution, and add a mixture of acetonitrile for liquid chromatography and the mobile phase A (3:2) to make exactly 100 mL. Pipet 0 – 3 89.5 10.5 3 – 48 89.5 → 31.5 10.5 → 68.5 48 – 68 31.5 68.5 Flow rate: 1.0 mL per minute. Time span of measurement: For 68 minutes after injec-tion, beginning after the solvent peak. System suitability— Test for required detectability: To exactly 2 mL of the standard solution add a mixture of acetonitrile for liquid chromatography and the mobile phase A (3:2) to make ex-actly 20 mL. Confirm that the peak area of clopidogrel ob-tained with 10 mL of this solution is equivalent to 7 to 13z of that with 10 mL of the standard solution. System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of clopidogrel are not less than 60,000 and not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of clopidogrel is not more than 2.0z. Enantiomer—Dissolve 0.10 g of Clopidogrel Sulfate in 25 mL of ethanol (99.5) for liquid chromatography, add heptane for liquid chromatography to make 50 mL, and use this solution as the sample solution. Pipet 2.5 mL of the sample solution, and add a mixture of ethanol (99.5) for liq-uid chromatography and heptane for liquid chromatography (1:1) to make exactly 50 mL. Pipet 5 mL of this solution, add a mixture of ethanol…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 45 mg each of Clopidogrel Sulfate and Clopidogrel Sulfate RS (separately, determine the water <2.48> in the same manner as Clopidogrel Sulfate), and dissolve them separately in the mobile phase to make ex-actly 50 mL. Take exactly 7 mL of each solution, add separately the mobile phase to make exactly 50 mL, and use these solutions as the sample solution and the standard solu-tion, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine the peak areas, AT and AS, of clopidogrel in each solution. is about 8 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of clopidogrel are not less than 4500 and not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of clopidogrel is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

clotiazepam
type: ChemicalDrugMonograph
pref label:
  en: Clotiazepam
  ja: クロチアゼパム
monograph id: JP18-clotiazepam
publisher: JP
status: Official
version: 18
molecular formula: C16H15ClN2OS
molecular weight: 318.82
cas number: 33671-46-4
definition:
  en: Clotiazepam, when dried, contains not less than 98.
appearance:
  en: Clotiazepam occurs as white to light yellow-white, crystals or crystalline powder. It is odorless, and has a slightly bitter taste. It is very soluble in chloroform, freely soluble in metha-nol, in ethanol (95), in acetone, in acetic acid (100) and in ethyl acetate, soluble in diethyl ether, and practically insolu-ble in water. It dissolves in 0.1 mol/L hydrochloric acid TS. It is gradually colored by light. of Clotiazepam, according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.25 g of Clotiazepam in 10 mL of acetone, and use this solution as the sample so-lution. Pipet 1 mL of the sample solution, add acetone to make exactly 20 mL, pipet 2 mL of this solution, add ace-tone to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of chlo-roform and acetone (5:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 809C, 3 hours). Residue on ignition <2.44> not more than 0.1z (1 g).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Clotiazepam in 3 mL of sulfuric acid: the solution shows a light yellow fluores-cence under ultraviolet light (main wavelength: 365 nm). Determine the absorption spectrum of a solution of Clotiazepam in 0.1 mol/L hydrochrolic acid TS (1 in 100,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Prepare the test solution with 0.01 g of Clotiazepam as directed under Oxygen Flask Combustion Method <1.06>, using 10 mL of diluted hydrogen peroxide (30) (1 in 5) as the absorbing liquid. Apply a small amount of water to the up-per part of the Apparatus A, pull out C carefully, wash C, B and the inner side of A with 15 mL of methanol, and use the obtained solution as the test solution. Add 0.5 mL of dilute nitric acid to 15 mL of the test solution: this solution re-sponds to Qualitative Tests <1.09> (2) for chloride. The remaining test solution responds to Qualitative Tests <1.09> for sulfate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Clotiazepam in 10 mL of ethanol (95): the solution is clear and is not more colored than the following control solution. Control solution: To 5 mL of Matching Fluid C add 0.01 mol/L hydrochloric acid TS to make 10 mL. Chloride <1.03>—To 1.0 g of Clotiazepam add 50 mL of water, shake for 30 minutes, and filter. To 30 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.25 mL of 0.01 mol/L hy-drochloric acid VS (not more than 0.015z). Heavy metals <1.07>—Proceed with 2.0 g of Clotia- zepam according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Clotiazepam, previ-ously dried, dissolve in 80 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid (potentiometric titra- tion). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 31.88 mg of C H ClN OS 16 15 2 Identification (1) Dissolve 0.01 g of Clotiazepam in 3 mL of sulfuric acid: the solution shows a light yellow fluores-cence under ultraviolet light (main wavelength: 365 nm). Determine the absorption spectrum of a solution of Clotiazepam in 0.1 mol/L hydrochrolic acid TS (1 in 100,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Prepare the test solution with 0.01 g of Clotiazepam as directed under Oxygen Flask Combustion Method <1.06>, using 10 mL of diluted hydrogen peroxide (30) (1 in 5) as the absorbing liquid. Apply a small amount of water to the up-per part of the Apparatus A, pull out C carefully, wash C, B and the inner side of A with 15 mL of methanol, and use the obtained solution as the test solution. Add 0.5 mL of dilute nitric acid to 15 mL of the test solution: this solution re-sponds to Qualitative Tests <1.09> (2) for chloride. The remaining test solution responds to Qualitative Tests <1.09> for sulfate. Melting point <2.60> 106 – 1099C Purity (1) Clarity and color of solution—Dissolve 1.0 g of Clotiazepam in 10 mL of ethanol (95): the solution is clear and is not more colored than the following control solution. Control solution: To 5 mL of Matching Fluid C add 0.01 mol/L hydrochloric acid TS to make 10 mL. Chloride <1.03>—To 1.0 g of Clotiazepam add 50 mL of water, shake for 30 minutes, and filter. To 30 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control sol…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

clotrimazole
type: ChemicalDrugMonograph
pref label:
  en: Clotrimazole
  ja: クロトリマゾール
monograph id: JP18-clotrimazole
publisher: JP
status: Official
version: 18
molecular formula: C22H17ClN2
molecular weight: 344.84
definition:
  en: Clotrimazole, when dried, contains not less than 98.
appearance:
  en: Clotrimazole occurs as a white, crystalline powder. It is odorless and tasteless. It is freely soluble in dichloromethane and in acetic acid (100), soluble in N,N-dimethylformamide, in methanol and in ethanol (95), slightly soluble in diethyl ether, and practi-cally insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 0.1 g of Clotrimazole add 10 mL of 5 mol/L hydrochloric acid TS, dissolve by heating, and cool. To this solution add 3 drops of Reinecke salt TS: a light red precipitate is produced. Determine the absorption spectrum of a solution of Clotrimazole in methanol (1 in 5000) as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Clotrimazole, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Clotrimazole as directed under Flame Coloration Test <1.04> (2): a green color appears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Clotrimazole in 10 mL of dichloromethane: the solution is clear and colorless. Chloride <1.03>—Dissolve 1.0 g of Clotrimazole in 40 mL of N,N-dimethylformamide, add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.60 mL of 0.01 mol/L hydrochloric acid VS, 40 mL of N,N-dimethylformamide, 6 mL of dilute nitric acid and water to make 50 mL (not more than 0.021z). Sulfate <1.14>—Dissolve 0.5 g of Clotrimazole in 10 mL of methanol, and add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solu-tion as the test solution. Prepare the control solution with 0.05 mL of 0.005 mol/L sulfuric acid VS, 10 mL of metha-nol, 1 mL of dilute hydrochloric acid and water to make 50 mL (not more than 0.048z). Heavy metals <1.07>—Proceed with 2.0 g of Clotrimazole according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Clotrimazole according to Method 3, and perform the test ‌800 (not more than 2 ppm). Imidazole—Dissolve 0.10 g of Clotrimazole in ex-actly 10 mL of dichloromethane, and use this solution as the sample solution. Separately, dissolve 25 mg of imidazole for thin-layer chromatography in dichloromethane to make exactly 50 mL. Pipet 5 mL of this solution, add dichloro-methane to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of methanol and chloroform (3:2) to a distance of about 10 cm, and air-dry the plate. Spray evenly sodium hypochlorite TS on the plate, and air-dry the plate for 15 minutes, then spray ev…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.35 g of Clotrimazole, pre-viously dried, and dissolve in 80 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 34.48 mg of C22H17ClN2
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

cloxazolam
type: ChemicalDrugMonograph
pref label:
  en: Cloxazolam
  ja: クロキサゾラム
monograph id: JP18-cloxazolam
publisher: JP
status: Official
version: 18
molecular formula: C17H14Cl2N2O2
molecular weight: 349.21
cas number: 24166-13-0
definition:
  en: Cloxazolam, when dried, contains not less than 99.
appearance:
  en: Cloxazolam occurs as white, crystals or crys-talline powder. It is odorless and tasteless. It is freely soluble in acetic acid (100), sparingly soluble in dichloromethane, slightly soluble in ethanol (99.5) and in diethyl ether, very slightly soluble in ethanol (95), and practi-cally insoluble in water. It dissolves in dilute hydrochloric acid. It is gradually colored by light. Melting point: about 2009C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Cloxazolam in 10 mL of ethanol (99.5) by heating, and add 1 drop of hydrochloric acid: the solution shows a light yellow color and a yellow-green fluorescence under ultraviolet light (main wavelength: 365 nm). Add 1 mL of sodium hydroxide TS to this solution: the color and fluorescence of this solution disappear immedi-ately. Dissolve 0.01 g of Cloxazolam in 5 mL of dilute hy-drochloric acid by heating in a water bath for 10 minutes. After cooling, 1 mL of this solution responds to Qualitative Tests <1.09> for primary aromatic amines. Place 2 g of Cloxazolam in a 200-mL flask, add 50 mL of ethanol (95) and 25 mL of sodium hydroxide TS, and boil under a reflux condenser for 4 hours. After cooling, neutralize with dilute hydrochloric acid, and extract with 30 mL of dichloromethane. Dehydrate with 3 g of anhydrous sodium sulfate, filter, and evaporate the dichloromethane of the filtrate. Dissolve the residue in 5 mL of methanol by heating on a water bath, and cool immediately in an ice bath. Collect the crystals, and dry the crystals is vacuum at 609C for 1 hour: it melts <2.60> between 879C and 919C. Determine the absorption spectrum of a solution of Cloxazolam in ethanol (99.5) (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare ‌802 the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave-lengths. Proceed with Cloxazolam as directed under Flame Coloration Test <1.04> (2), and perform the test: a green color appears. Cocaine Hydrochloride
type: PharmacopoeiaMonograph

cocaine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cocaine Hydrochloride
  ja: コカイン塩酸塩
monograph id: JP18-cocaine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C17H21NO4.HCl
molecular weight: 339.81
definition:
  en: Cocaine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Cocaine Hydrochloride occurs as colorless crystals or a white crystalline powder. It is very soluble in water, freely soluble in ethanol (95) and in acetic acid (100), slightly soluble in acetic anhydride, and practically insoluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cocaine Hydrochloride in 0.01 mol/L hydro-chloric acid TS (1 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum 1: both spectra exhibit similar intensities of absorption at the same wavelengths. Sepa-rately, determine the absorption spectrum of a solution of Cocaine Hydrochloride in 0.01 mol/L hydrochloric acid TS (1 in 50,000) as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum 2: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Cocaine Hydrochloride, previously dried, as directed in the potassium bromide disk method under the Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Cocaine Hydrochloride (1 in 50) re-sponds to Qualitative Tests <1.09> (2) for chloride. D Optical rotation <2.49> [a]20: －70 – －739(after drying, 0.5 g, water, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—To 1.0 g of Cloxazolam add 50 mL of water, allow to stand for 1 hour with occasional shaking, and filter. To 25 mL of this filtrate add 6 mL of dilute nitric acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the con-trol solution with 0.20 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.014z). Heavy metals <1.07>—Proceed with 1.0 g of Clox- azolam according to Method 2, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 20 ppm). Arsenic <1.11>—Place 1.0 g of Cloxazolam in a Kjel- dahl flask, add 5 mL of sulfuric acid and 5 mL of nitric acid, and heat gently. Repeat the addition of 2 to 3 mL of nitric acid at times, and continue heating until a colorless to light yellow solution is obtained. After cooling, add 15 mL of saturated ammonium oxalate solution, and heat the solution until dense white fumes are evolved, and evaporate to a volume of 2 to 3 mL. After cooling, dilute with water to 10 mL, and perform the test with this solution as the test solu-tion (not more than 2 ppm). Related substances—Dissolve 0.05 g of Cloxazolam in 10 mL of dichloromethane, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add dichloromethane to make exactly 200 mL, and use this solu-tion as the standard solution. Perform the test with these so-lutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solu-tion on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Immediately after air-drying, develop the plate with a mixture of toluene and acetone (5:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot from the sample solution are not more intense than that from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hou…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Cloxazolam, previ-ously dried, and dissolve in 50 mL of acetic acid (100). Titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue to blue-green (indicator: 2 drops of crystal violet TS). Perform a blank determination in the same menner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 34.92 mg of C17H14Cl2N2O2
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.

cod-liver-oil
type: ChemicalDrugMonograph
pref label:
  en: Cod Liver Oil
  ja: 肝油
monograph id: JP18-cod-liver-oil
publisher: JP
status: Official
version: 18
definition:
  en: Cod Liver Oil is the fatty oils obtained from fresh livers and pyloric appendages of Gadus macrocephalus Tilesius or Theragra chalcogramma Pallas (Gadidae). Cod Liver Oil contains not less than 2000 Vitamin A Units and not more than 5000 Vitamin A Units per g.
appearance:
  en: Cod Liver Oil is a yellow to orange oily liquid. It has a characteristic, slightly fishy odor and a mild taste. It is miscible with chloroform. It is slightly soluble in ethanol (95), and practically insolu-ble in water. It is decomposed by air or by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Dissolve 0.1 g of Cod Liver Oil in 10 mL of chloroform, and to 1 mL of this solution add 3 mL of an-timony (III) chloride TS: a blue color develops immediately, but the color fades rapidly. Specific gravity <1.13> d 20: 0.918 – 0.928 Acid value <1.13> Not more than 1.7. Saponification value <1.13> 180 – 192 Unsaponifiable matter <1.13> Not more than 3.0z. Iodine value <1.13> 130 – 170
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Rancidity—No unpleasant odor of rancid oil is per-ceptible on warming Cod Liver Oil.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Proceed with about 0.5 g of Cod Liver Oil, accu-rately weighed, as directed in Method 2 under the Vitamin A Determination <2.55>, and perform the test.
storage conditions:
  en: Containers—Tight containers.

codeine-phosphate-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Codeine Phosphate Hydrate
  ja: コデインリン酸塩水和物
monograph id: JP18-codeine-phosphate-hydrate
publisher: JP
status: Official
version: 18
appearance:
  en: Codeine Phosphate Hydrate occurs as white to yellowish white, crystals or crystalline powder. It is freely soluble in water and in acetic acid (100), slightly soluble in methanol and in ethanol (95), and practically in-soluble in diethyl ether. The pH of a solution of 1.0 g of Codeine Phosphate Hy-drate in 10 mL of water is between 3.0 and 5.0. It is affected by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Codeine Phosphate Hydrate (1 in 10,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Codeine Phosphate Hydrate, previously dried at 1059C for 4 hours, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Codeine Phosphate Hydrate (1 in 20) responds to Qualitative Tests <1.09> (1) for phosphate. D Optical rotation <2.49> [a]20: －98 – －1029(0.4 g calcu-lated on the anhydrous basis, water, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Perform the test with 0.5 g of Codeine Phosphate Hydrate. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.20 g of Codeine Phosphate Hydrate. Prepare the control solution with 1.0 mL of 0.005 mol/L sulfuric acid VS (not more than 0.240z). Related substances—Dissolve 0.20 g of Codeine Phosphate Hydrate in 10 mL of a mixture of 0.01 mol/L hydrochloric acid TS and ethanol (99.5) (4:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of 0.01 mol/L hydrochloric acid TS and ethanol (99.5) (4:1) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethanol (99.5), toluene, acetone and ammonia solution (28) (14:14:7:1) to a distance of about 10 cm, and air-dry the ‌804 plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Water <2.48> 1.5 – 3.0z (0.5 g, volumetric titration, direct titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Dissolve about 0.5 g of Codeine Phosphate Hydrate, accurately weighed, in 70 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue to greenish blue (indicator: 3 drops of crystal violet TS). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 39.74 mg of C18H21NO3.H3PO4
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

colchicine
type: ChemicalDrugMonograph
pref label:
  en: Colchicine
  ja: コルヒチン
monograph id: JP18-colchicine
publisher: JP
status: Official
version: 18
molecular formula: C22H25NO6
molecular weight: 399.44
definition:
  en: Colchicine contains not less than 97.
appearance:
  en: Colchicine occurs as a yellowish white powder. It is very soluble in methanol, freely soluble in N,N-dimethylformamide, in ethanol (95) and in acetic anhydride, and sparingly soluble in water. It is colored by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Colchicine in ethanol (95) (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) To 1 g of potassium bromide for infrared absorption spectrum add 0.5 mL of a solution of Colchicine in methanol (1 in 50), grind thoroughly, and dry in vacuum at 809C for 1 hour. Determine the infrared absorption spectrum of this powder as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －235 – －2509(0.1 g calcu-lated on the anhydrous basis and corrected by the amount of ethyl acetate, ethanol (95), 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Colchicine—Dissolve 0.10 g of Colchicine in 10 mL of water, and to 5 mL of this solution add 2 drops of iron (III) chloride TS: no definite green color develops. Chloroform and ethyl acetate—Weigh accurately about 0.6 g of Colchicine, dissolve in exactly 2 mL of the internal standard solution, add N,N-dimethylformamide to make 10 mL, and use this solution as the sample solution. Separately, weigh 0.30 g of chloroform using a 100-mL volu-metric flask containing about 20 mL of N,N-dimethylfor-mamide, and add N,N-dimethylformamide to make exactly 100 mL. Pipet 2 mL of this solution, add N,N-dimethylfor-mamide to make exactly 200 mL, and use this solution as the standard solution (1). Separately, weigh accurately about 1.8 g of ethyl acetate using a 100-mL volumetric flask con-taining about 20 mL of N,N-dimethylformamide, and add N,N-dimethylformamide to make exactly 100 mL. Pipet 2 mL of this solution, add exactly 2 mL of the internal stand-ard solution and N,N-dimethylformamide to make 10 mL, and use this solution as the standard solution (2). Perform the test with exactly 2 mL each of the sample solution and standard solutions (1) and (2) as directed under Gas Chro-matography <2.02> according to the following conditions: Column temperature: 609C for 7 minutes, then up to 1009C at a rate of 409C per minute if necessary, and hold at 1009C for 10 minutes. Injection port temperature: A constant temperature of about 1309C. Detector temperature: A constant temperature of about 2009C. Carrier gas: Helium. Flow rate: Adjust so that the retention time of ethyl ace-tate is about 3 minutes. Split ratio: 1:20. System suitability— Test for required detectability: Pipet 2 mL of the standard solution (2), and add N,N-dimethylformamide to make exactly 25 mL. Pipet 1 mL of this solution, and add N,N-dimethylformamide to make exactly 50 mL. Confirm that the peak area of ethyl acetate obtained with 2 mL of this so-lution is equivalent to 0.11 to 0.21z of that with 2 mL of the stand…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Colchicine, dissolve in 25 mL of acetic anhydride, and titrate <2.50> with 0.05 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.05 mol/L perchloric acid VS ＝ 19.97 mg of C22H25NO6
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

colestimide
type: ChemicalDrugMonograph
pref label:
  en: Colestimide
  ja: コレスチミド
monograph id: JP18-colestimide
publisher: JP
status: Official
version: 18
cas number: 95522-45-5
definition:
  en: Colestimide is an anion exchange resin, composed of a copolymer of 2-methylimidazole and 1-chloro-2,3-epoxypropane. It contains not less than 18.
appearance:
  en: Colestimide occurs as a white to pale yellow-white powder. It is practically insoluble in water and in ethanol (99.5). It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Colestimide, previously dried, as directed in the potas-sium chloride disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp-tion at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Take 2.0 g of Coles-timide in a porcelain or platinum crucible, and carbonize by weakly heating. After cooling, add 10 mL of a solution of magnesium nitrate hexahydrate in ethanol (95) (1 in 10) and 5 mL of hydrogen peroxide (30), and ignite the ethanol. After cooling, add 1 mL of sulfuric acid, then, proceed ac-cording to Method 4, and perform the test. Prepare the con-trol solution as follows: To 10 mL of a solution of magne-sium nitrate hexahydrate in ethanol (95) (1 in 10) add 5 mL of hydrogen peroxide (30), and ignite the ethanol. After cooling, add 1 mL of sulfuric acid, then, proceed in the same manner as for the test solution, and add 2.0 mL of Standard Lead Solution and water to make 50 mL (not more than 10 ppm). (2) Related substances—To exactly 0.50 g of Colestimide add exactly 20 mL of water, shake for 1 hour, centrifuge, and use the supernatant liquid as the sample solution. Deter-mine the absorbance of the sample solution at 210 nm as di-rected under Ultraviolet-visible Spectrophotometry <2.24>: the absorbance is not more than 0.50. Loss on drying <2.41> Not more than 10.0z (1 g, in vacu-um, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g). Degree of swelling Weigh accurately about 1 g of Coles-timide, put in a 25-mL glass stoppered measuring cylinder (about 11 mm in inside diameter), add 23 mL of water, shake for 2 minutes, and add water to make 25 mL. After standing for 2 hours, measure the volume of the resin layer, and determine the volume per g, calculated on the dried basis: the volume is 12 – 18 mL/g.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Chlorine—Weigh accurately about 0.2 g of Colestimide, add 50 mL of water, and shake. Add 1 mL of nitric acid and 25 mg of potassium nitrate, shake, and titrate <2.50> with 0.1 mol/L silver nitrate VS (potentiometric titra- tion). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L silver nitrate VS ＝ 3.545 mg of Cl (2) Exchange capacity—Weigh accurately about 0.45 g of sodium cholate hydrate (separately determine the water), dissolve in water to make exactly 100 mL, and use this solu-tion as the sodium cholate standard stock solution. Sepa-rately, weigh accurately about 30 mg of Colestimide, add ex-actly 30 mL of the sodium cholate standard stock solution, shake for 1 hour, and centrifuge or filter through a mem-brane filter with a pore size not exceeding 0.8 mm. Pipet 5 mL of the supernatant liquid or the filtrate, add exactly 5 mL of the internal standard solution, and use this solution as the sample solution. Separately, pipet 5 mL of the sodium cholate standard stock solution, add exactly 5 mL of the in-ternal standard solution, and use this solution as the stand-ard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi-tions, and calculate the ratios, QT and QS, of the peak area of cholic acid to that of the internal standard. Exchanged amount (g) of cholic acid per g of Colestimide, calculated on the dried basis ＝ MS/MT × (QS － QT)/QS × 3/10 × 0.947 MS: Amount (mg) of sodium cholate hydrate taken, calcu- ‌JP XVIII Official Monographs / Colestimide Tablets 809‌ lated on the anhydrous basis MT: Amount (mg) of Colestimide taken, calculated on the dried basis Internal standard solution—A solution of butyl parahy-droxybenzoate in acetonitrile (1 in 80,000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 220 nm). Column: A stainless steel column 4.6 mm in inside…
storage conditions:
  en: Containers—Tight containers.

colistin-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Colistin Sulfate
  ja: コリスチン硫酸塩
monograph id: JP18-colistin-sulfate
publisher: JP
status: Official
version: 18
definition:
  en: Colistin Sulfate is the sulfate of a mixture of peptide substances having antibacterial activity produced by the growth of Bacillus polymyxa var. colistinus. It, when dried, contains not less than 16,000 units per mg.
appearance:
  en: Colistin Sulfate occurs as a white to light yel-low-white powder. It is freely soluble in water, and practically insoluble in ethanol (99.5). It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 20 mg of Colistin Sulfate in 2 mL of water, add 0.5 mL of sodium hydroxide TS, then add 5 drops of copper (II) sulfate TS while shaking: a purple color develops. Dissolve 50 mg of Colistin Sulfate in 10 mL of diluted hydrochloric acid (1 in 2). Transfer 1 mL of this solu-tion in a tube for hydrolysis, seal, and heat at 1359C for 5 hours. After cooling, open the tube, and evaporate the con-tent to dryness until the odor of hydrochloric acid is no more perceptible. Dissolve the residue in 0.5 mL of water, and use this solution as the sample solution. Separately, dissolve 20 mg each of L-leucine, L-threonine, phenylalanine and L-ser-ine in 10 mL of water, and use these solutions as the stand-ard solution (1), (2), (3) and (4). Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 1 mL each of the sample solution and standard solution (1), (2), (3) and (4) on a plate of cellulose for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, acetic acid (100), water, pyridine and ethanol (99.5) (60:15:10:6:5) to a distance of about 10 cm, and dry the plate at 1059C for 10 minutes. Spray evenly ninhydrin TS on the plate, and heat at 1109C for 5 minutes: three principal spots are obtained from the sample solution, the Rf values of two spots of them are the same with those of the cor-responding spots obtained from the standard solution (1) and the standard solution (2), and the Rf value of the rest principal spot is about 0.1. No spot is observed at the posi-tion corresponding to the spots from the standard solution (3) and the standard solution (4). A solution of Colistin Sulfate (1 in 20) responds to Qualitative Tests <1.09> (1) for sulfate. D Optical rotation <2.49> [a]20: －63 – －739(1.25 g, after drying, water, 25 mL, 100 mm). pH <2.54> The pH of a solution obtained by dissolving Related substances—Dissolve 50 mg of Colistin Sul-fate in 10 mL of water, and use this solution as the sample solution. Pip…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfuric acid—Weigh accurately about 0.25 g of previously dried Colistin Sulfate, dissolve in a suitable amount of water, adjust the pH to 11 with ammonia solution (28), and add water to make 100 mL. To this solution add exactly 10 mL of 0.1 mol/L barium chloride VS and 50 mL of ethanol (99.5), and titrate with <2.50> 0.1 mol/L disodium dihydrogen ethylenediamine tetraacetate VS until the blue-purple color of the solution disappears (indicator: 0.5 mg of phthalein purple): the amount of sulfuric acid (SO4) is 16.0 to 18.0z. Colistin A Sulfate C H N O .21/ H SO : 1414.66 Each mL of 0.1 mol/L barium chloride VS 53 100 16 13 2 2 4 ＝ 9.606 mg of SO4 Colistin B Sulfate C52H98N16O13.21/2H2SO4: 1400.63 [1264-72-8] Colistin Sulfate is the sulfate of a mixture of peptide substances having antibacterial activity produced by the growth of Bacillus polymyxa var. colistinus. It, when dried, contains not less than 16,000 units per mg. The potency of Colistin Sulfate is expressed as unit calculated from the amount of colistin A (C53H100N16O13: 1169.46). One unit of Colistin Sulfate is equivalent to 0.04 mg of colistin A (C53H100N16O13). Description Colistin Sulfate occurs as a white to light yel-low-white powder. It is freely soluble in water, and practically insoluble in ethanol (99.5). It is hygroscopic. Identification (1) Dissolve 20 mg of Colistin Sulfate in 2 mL of water, add 0.5 mL of sodium hydroxide TS, then add 5 drops of copper (II) sulfate TS while shaking: a purple color develops. Dissolve 50 mg of Colistin Sulfate in 10 mL of diluted hydrochloric acid (1 in 2). Transfer 1 mL of this solu-tion in a tube for hydrolysis, seal, and heat at 1359C for 5 hours. After cooling, open the tube, and evaporate the con-tent to dryness until the odor of hydrochloric acid is no more perceptible. Dissolve the residue in 0.5 mL of water, and use this solution as the sample solution. Separately, dissolve 20 mg each of L-leucine, L-threonine, phenylalanine and L-ser-ine in 10 mL of w…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform the test according to the Cylinder-plate method as directed under Microbial Assay for Antibiotics <4.02> according to the following conditions. Test organism—Escherichia coli NIHJ Culture medium—Dissolve 10.0 g of peptone, 30.0 g of sodium chloride, 3.0 g of meat extract and 15.0 g of agar in 1000 mL of water, adjust the pH with sodium hydroxide TS so that the solution will be 6.5 to 6.6 after sterilization, and use as the agar media for seed layer and for base layer. Standard solutions—Weigh accurately an amount of Colistin Sulfate RS, previously dried, equivalent to about 1,000,000 units, dissolve in phosphate buffer solution (pH 6.0) to make exactly 10 mL, and use this solution as the standard stock solution. Keep the standard stock solution at not exceeding 109C, and use within 7 days. Take exactly a suitable amount of the standard stock solution before use, add phosphate buffer solution (pH 6.0) to make solutions so that each mL contains 10,000 units and 2500 units, and use these solutions as the high concentration standard solution and the low concentration standard solution, respectively. Sample solutions—Weigh accurately an amount of Colistin Sulfate, previously dried, equivalent to about 1,000,000 units, and dissolve in phosphate buffer solution (pH 6.0) to make exactly 10 mL. Take exactly a suitable amount of this solution, add phosphate buffer solution (pH 6.0) to make solutions so that each mL contains 10,000 units and 2500 units, and use these solutions as the high concen-tration sample solution and the low concentration sample so-lution, respectively.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

compound-iodine-glycerin
type: ChemicalDrugMonograph
pref label:
  en: Compound Iodine Glycerin
  ja: 複方ヨード・グリセリン
monograph id: JP18-compound-iodine-glycerin
publisher: JP
status: Official
version: 18
definition:
  en: Compound Iodine Glycerin contains not less than w/vz and not more than 1.
appearance:
  en: Compound Iodine Glycerin is a red-brown, viscous liquid. It has a characteristic odor. Specific gravity d 20: about 1.23
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) The colored solution obtained in the Assay (1) acquires a red color. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhibits a maximum be-tween 510 nm and 514 nm (iodine). The colored solution obtained in the Assay (2) ac-quires a red color. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectro-photometry <2.24>: it exhibits a maximum between 510 nm and 514 nm (potassium iodide). The colored solution obtained in the Assay (4) has a yellow color. Determine the absorption spectrum of this so-lution as directed under Ultraviolet-visible Spectrophotome-try <2.24>: it exhibits a maximum between 401 nm and 405 nm (phenol). Take 1 mL of Compound Iodine Glycerin in a glass-stoppered test tube, add 10 mL of ethanol (95), and mix. Then add 2 mL of sodium hydroxide TS, add 1 mL of a so-lution of copper (II) chloride dihydrate in ethanol (95) (1 in 10), and shake: a blue color develops (glycerin).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Iodine—Measure the specific gravity of Com-pound Iodine Glycerin according to Method 2 under Deter-mination of Specific gravity and density <2.56>. Weigh ex-actly about 7 mL of it, add ethanol (95) to make exactly 200 mL, and use this solution as the sample solution. On the other hand, weigh accurately about 80 mg of iodine for assay and about 0.17 g of potassium iodide for assay, previously dried at 1059C for 4 hours, dissolve in ethanol (95) to make exactly 200 mL, and use this solution as the standard solu- ‌1172 tion. Pipet 3 mL each of the sample solution and the stand-ard solution into 50-mL separators, to each add exactly 10 mL of a mixture of chloroform and hexane (2:1) and 15 mL of water successively, and shake immediately and vigor-ously. Separate the chloroform-hexane layers [use the water layers in (2)], and filter through a pledget of cotton. Deter-mine the absorbances of the filtrates, AT and AS, at 512 nm as directed under Ultraviolet-visible Spectrophotometry <2.24>, using a mixture of chloroform and hexane (2:1) as the blank. solution, and use so obtaind solution as the standard solu-tion. Pipet 3 mL each of the sample solution and standard solution, to each add 2 mL of dilute hydrochloric acid, and place in a water bath at 309C. Allow to stand for 10 minutes, and add exactly 2 mL of a solution of sodium nitrite (1 in 100), shake, and allow to stand at 309C for 60 minutes. Add dilute potassium hydroxide-ethanol TS to make exactly 25 mL, and determine the absorbances of these solutions, AT and AS, at 403 nm as directed under Ultraviolet-visible Spec-trophotometry <2.24>, using the solution prepared in the Amount (mg) of iodine (I) ＝ MS × AT/AS same manner with 3 mL of water instead of the sample solu- tion as the blank. MS: Amount (mg) of iodine for assay taken Potassium iodide—Separate the water layers of the sample solution and the standard solution obtained in (1), pipet 10 mL of each of the water layers, and to each add 1 mL of diluted dilute…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

compound-methyl-salicylate-spirit
type: ChemicalDrugMonograph
pref label:
  en: ‌Compound Methyl Salicylate Spirit‌
  ja: 複方サリチル酸メチル精
monograph id: JP18-compound-methyl-salicylate-spirit
publisher: JP
status: Official
version: 18
appearance:
  en: Compound Methyl Salicylate Spirit is a red-dish yellow liquid, having a characteristic odor and a burn-ing taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Shake 1 mL of Compound Methyl Salicylate Spirit with 5 mL of dilute ethanol, and add 1 drop of iron (III) chloride TS: a purple color is produced (methyl salicylate). (2) Shake thoroughly 1 mL of Compound Methyl Salicy-late Spirit with 10 mL of chloroform, and use this solution as the sample solution. Dissolve 40 mg of methyl salicylate in 10 mL of chloroform, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on the plate of silica gel with fluorescent indicator for thin-layer chromatog-raphy. Develop the plate with a mixture of hexane and chlo-roform (4:1) to a distance of about 10 cm, air-dry the plate, and examine under ultraviolet light (main wavelength: 254 nm): the spots obtained from the sample solution and the standard solution show the same Rf value. Spray evenly iron (III) chloride TS upon the plate: the spot from the standard solution and the corresponding spot from the sample solu-tion reveal a purple color.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

compound-salicylic-acid-spirit
type: ChemicalDrugMonograph
pref label:
  en: Compound Salicylic Acid Spirit
  ja: 複方サリチル酸精
monograph id: JP18-compound-salicylic-acid-spirit
publisher: JP
status: Official
version: 18
definition:
  en: Compound Salicylic Acid Spirit contains not less than 1.
appearance:
  en: Compound Salicylic Acid Spirit is a clear, col-orless to light red liquid. Specific gravity d 20: about 0.88
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of Compound Salicylic Acid Spirit add hydrochloric acid-potassium chloride buffer solu-tion (pH 2.0) to make 200 mL, and to 5 mL of this solution add 5 mL of a solution of iron (III) nitrate enneahydrate (1 in 200): a red-purple color is produced (salicylic acid). To 1 mL of Compound Salicylic Acid Spirit add 20 mL of water and 5 mL of dilute hydrochloric acid, and ex-tract with 20 mL of diethyl ether. Wash the diethyl ether ex-tract with two 5-mL portions of sodium hydrogen carbonate TS, and extract with 10 mL of dilute sodium hydroxide TS. Shake 1 mL of the extract with 1 mL of sodium nitrite TS and 1 mL of dilute hydrochloric acid, allow to stand for 10 minutes, and add 3 mL of sodium hydroxide TS: a yellow color is produced (phenol). To 0.5 mL of Compound Salicylic Acid Spirit add 5 mL of dilute hydrochloric acid, extract with 5 mL of chlo-roform, and use the extract as the sample solution (1). To 2 mL of Compound Salicylic Acid Spirit add 5 mL of dilute hydrochloric acid, extract with 5 mL of chloroform, wash the extract with two 5-mL portions of sodium hydrogen car-bonate TS, and use the chloroform extract as the sample so- ＝ MS × AT/AS 7 6 3 lution (2). Separately, dissolve 0.01 g each of salicylic acid and phenol in 5 mL each of chloroform, and use both solu- MS: Amount (mg) of salicylic acid for assay taken
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

concentrated-glycerol
type: ChemicalDrugMonograph
pref label:
  en: Concentrated Glycerol
  ja: 濃グリセリン
monograph id: JP18-concentrated-glycerol
publisher: JP
status: Official
version: 18
molecular formula: C3H8O3
molecular weight: 92.09
appearance:
  en: Concentrated Glycerin is a clear, colorless and viscous liquid. It has a sweet taste. It is miscible with water and with ethanol (99.5). It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Concentrated Glycerin as directed in the liquid film method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Refractive index <2.45> n20: Not less than 1.470. Specific gravity <2.56> d 20: Not less than 1.258.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Color—Place 50 mL of Concentrated Glycerin in a Nessler tube, and observe downward: the solution has no more color than the following control solution. Control solution: Pipet 0.40 mL of Iron (III) Chloride CS into a Nessler tube, and add water to make 50 mL. Acidity or alkalinity—To 2 mL of Concentrated Glycerin add 8 mL of water and mix: the solution is neutral. Chloride <1.03>—Take 10.0 g of Concentrated Glyce- rin, and perform the test. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.001z). Sulfate <1.14>—Take 10.0 g of Concentrated Glyce- rin, and perform the test. Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not more than 0.002z). Ammonium—To 5 mL of Concentrated Glycerin add 5 mL of a solution of sodium hydroxide (1 in 10), and boil: the gas evolved does not change moistened red litmus paper to blue. Heavy metals <1.07>—Proceed with 5.0 g of Concen- trated Glycerin according to Method 1, and perform the test. Prepare the control solution with 2.5 mL of Standard Lead Solution (not more than 5 ppm). Calcium—To 5 mL of the solution obtained in (2) add 3 drops of ammonium oxalate TS: the solution remains unchanged. Arsenic <1.11>—Prepare the test solution with 1.0 g of Concentrated Glycerin according to Method 1, and per-form the test (not more than 2 ppm). Acrolein, glucose, or other reducing substances—To 1.0 g of Concentrated Glycerin add 1 mL of ammonia TS, mix, and warm in a water bath at 609C for 5 minutes: no yel-low color is produced. Take the solution out of the water bath, add 3 drops of silver nitrate TS immediately, and allow to stand in a dark place for 5 minutes: the color of the solu-tion does not change, and no turbidity is produced. Fatty acids and esters—Mix 50 g of Concentrated Glycerin with 50 mL of freshly boiled and cooled water, add 10 mL of 0.1 mol/L sodium hydroxide VS, accurately meas-ured, boil the mixture for 15 minutes, cool, and titrate <2.50> the excess …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Concentrated Glycerin, transfer into a glass-stoppered flask, add 50 mL of water, mix, add exactly 50 mL of sodium periodate TS, shake, and allow to stand in a dark place at a room tempera-ture for about 30 minutes. Add 10 mL of a mixture of water and ethylene glycol (1:1), allow to stand for about 20 minutes, add 100 mL of water, and titrate <2.50> with 0.1 mol/L sodium hydroxide VS (indicator: 2 drops of phenol-phthalein TS). Perform a blank determination in the same manner, and make the necessary correction. Each mL of 0.1 mol/L sodium hydroxide VS ＝ 9.209 mg of C3H8O3
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

condurango-fluidextract
type: ChemicalDrugMonograph
pref label:
  en: Condurango Fluidextract
  ja: コンズランゴ流エキス
monograph id: JP18-condurango-fluidextract
publisher: JP
status: Official
version: 18
appearance:
  en: Condurango Fluidextract is a brown liquid. It has a characteristic odor and a bitter taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Mix 1 mL of Condurango Fluidextract with 5 mL of water, filter, if necessary, and heat the clear solu-tion: turbidity is produced. However, it becomes almost clear upon cooling.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Heavy metals <1.07>—Prepare the test solution with 1.0 g of Condurango Fluidextract as direct under the Fluidextracts (4), and perform the test (not more than 30 ppm).
storage conditions:
  en: Containers—Tight containers.

containers-and-storage-containershermetic-containers-storagelight-resistant
type: ChemicalDrugMonograph
pref label:
  en: Containers and storage Containers—Hermetic containers. Storage—Light-resistant.
  ja: エフェドリン塩酸塩散 10
monograph id: JP18-containers-and-storage-containershermetic-containers-storagelight-resistant
publisher: JP
status: Official
version: 18
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 0.5 g of 10z Ephedrine Hydrochloride Powder add 100 mL of water, shake for 20 minutes, and filter. Determine the absorption spectrum of the filtrate as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhibits maxima between 249 nm and 253 nm, between 255 nm and 259 nm, and between 261 nm and 265 nm. Dissolution <6.10> When the test is performed at 50 revolu-tions per minute according to the Paddle method, using 900 mL of water as the dissolution medium, the dissolution rate in 15 minutes of 10z Ephedrine Hydrochloride Powder is not less than 85z. Start the test with about 0.25 g of 10z Ephedrine Hydro-chloride Powder, accurately weighed, withdraw not less than 20 mL of the medium at the specified minute after starting the test, and filter through a membrane filter with a pore size not exceeding 0.45 mm. Discard not less than 10 mL of the first filtrate, and use the subsequent filtrate as the sample so-lution. Separately, weigh accurately about 28 mg of ephe-drine hydrochloride for assay, previously dried at 1059C for 3 hours, and dissolve in water to make exactly 100 mL. Pipet 5 mL of this solution, add water to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of ephedrine in each solution. Dissolution rate (z) with respect to the labeled amount of ephedrine hydrochloride (C10H15NO.HCl) ＝ MS/MT × AT/AS × 9/10 MS: Amount (mg) of ephedrine hydrochloride for assay taken MT: Amount (g) of 10z Ephedrine Hydrochloride Pow-der taken Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Purity (4) under Ephedrin Hydrochloride. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the ab…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of 10z Ephedrine Hy-drochloride Powder, add 150 mL of water, and extract by sonicating for 10 minutes with occasional shaking. Shake more for 10 minutes, then add exactly 10 mL of the internal standard solution and water to make 200 mL, centrifuge, and use the supernatant liquid as the sample solution. Sepa-rately, weigh accurately about 40 mg of ephedrine hydro-chloride for assay, previously dried at 1059C for 3 hours, add exactly 10 mL of the internal standard solution to dis-solve, add water to make 200 mL, and use this solution as the standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of ephedrine to that of the internal standard. Amount (mg) of ephedrine hydrochloride (C10H15NO.HCl) ＝ MS × QT/QS MS: Amount (mg) of ephedrine hydrochloride for assay taken Internal standard solution—A solution of etilefrine hydro-chloride (1 in 500). Operating conditions— Detector, column, column temperature, mobile phase and flow rate: Perform as directed in the operating conditions in the Purity (4) under Ephedrine Hydrochloride. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the internal standard and ephedrine are eluted in this order with the resolution between these peaks being not less than 15. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of ephedrine to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

containers-and-storage-containerstight-containers-storagelight-resistant
type: ChemicalDrugMonograph
pref label:
  en: Containers and storage Containers—Tight containers. Storage—Light-resistant.
  ja: ジヒドロコデインリン酸塩散 1
monograph id: JP18-containers-and-storage-containerstight-containers-storagelight-resistant
publisher: JP
status: Official
version: 18
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the absorption spectrum of a so-lution of 1z Dihydrocodeine Phosphate Powder (1 in 100) as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhibits a maximum between 281 nm and 285 nm. Dissolution <6.10> When the test is performed at 50 revolu-tions per minute according to the Paddle method, using 900 mL of water as the dissolution medium, the dissolution rate in 15 minutes of 1z Dihydrocodeine Phosphate Powder is not less than 85z. Start the test with about 1 g of 1z Dihydrocodeine Phos-phate Powder, accurately weighed, withdraw not less than 20 mL of the medium at the specified minute after starting the test, and filter through a membrane filter with a pore size not exceeding 0.45 mm. Discard not less than 5 mL of the first filtrate, and use the subsequent filtrate as the sample so-lution. Separately, weigh accurately about 50 mg of dihydro-codeine phosphate for assay (separately determine the loss on drying <2.41> at 1059C for 4 hours), and dissolve in water to make exactly 100 mL. Pipet 2 mL of this solution, add water to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine the peak areas, AT and AS, of dihydrocodeine in each solution. ‌858 Dissolution rate (z) with respect to the labeled amount of dihydrocodeine phosphate (C18H23NO3.H3PO4) ＝ MS/MT × AT/AS × 9/5 MS: Amount (mg) of dihydrocodeine phosphate for assay taken, calculated on the dried basis MT: Amount (g) of 1z Dihydrocodeine Phosphate Pow-der taken Operating conditions— Proceed as directed in the operating conditions in the Assay. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry ing conditions, the relative standard deviation of the rat…
storage conditions:
  en: Containers—Tight containers.

containers-and-storage-containerstight-containers
type: ChemicalDrugMonograph
pref label:
  en: ◆Containers and storage Containers—Tight containers.◆
  ja: 10 塩化ナトリウム注射液
monograph id: JP18-containers-and-storage-containerstight-containers
publisher: JP
status: Official
version: 18
appearance:
  en: 10z Sodium Chloride Injection is a clear, col-orless liquid. It has a saline taste. It is neutral.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: 10z Sodium Chloride Injection responds to Qualitative Tests <1.09> for sodium salt and for chloride. Bacterial endotoxins <4.01> Less than 3.6 EU/mL. Extractable volume <6.05> It meets the requirement. Foreign insoluble matter <6.06> Perform the test according to Method 1: it meets the requirement. Insoluble particulate matter <6.07> It meets the require-ment. Sterility <4.06> Perform the test according to the Mem-brane filtration method: it meets the requirement.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Pipet 10 mL of 10z Sodium Chloride Injection, and add water to make exactly 100 mL. Pipet 20 mL of this solu-tion, add 30 mL of water, and titrate <2.50>, with vigorous shaking, with 0.1 mol/L silver nitrate VS (indicator: 3 drops of fluorescein sodium TS). Each mL 0.1 mol/L silver nitrate VS ＝ 5.844 mg of NaCl
storage conditions:
  en: Containers—Hermetic containers. Plastic containers for aqueous injections may be used.

containers-and-storage-containerswell-closed-contain-ers
type: ChemicalDrugMonograph
pref label:
  en: Containers and storage Containers—Well-closed contain-ers.
  ja: フェノバルビタール散 10
monograph id: JP18-containers-and-storage-containerswell-closed-contain-ers
publisher: JP
status: Official
version: 18
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of the sample solution obtained in the Assay as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhibits a maximum between 238 nm and 242 nm. (2) To 6 g of 10z Phenobarbital Powder add 150 mL of ethanol, shake well, and filter. Condense the filtrate on a water bath to about 5 mL, add about 50 mL of water, filter to collect the formed crystals, and dry them at 1059C for 2 hours. Determine the infrared absorption spectrum of the crystals as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolution <6.10> When the test is performed at 50 revolu-tions per minute according to the Paddle method, using 900 mL of water as the dissolution medium, the dissolution rate in 30 minutes of 10z Phenobarbital Powder is not less than 80z. Start the test with an accurately weighted about 0.3 g of 10z Phenobarbital Powder, withdraw not less than 20 mL of the medium at the specified minute after starting the test, and filter through a membrane filter with a pore size not exceeding 0.45 mm. Discard not less than 10 mL of the first filtrate, pipet 5 mL of the subsequent filtrate, add exactly 10 mL of boric acid-potassium chloride-sodium hydroxide buffer solution (pH 9.6) and use this solution as the sample solution. Separately, weigh accurately about 17 mg of phenobarbital for assay, previously dried at 1059C for 2 hours, and dissolve in water to make exactly 100 mL. Pipet 5 mL of this solution, and add water to make exactly 25 mL. Pipet 5 mL of this solution, add exactly 10 mL of boric acid-potassium chloride-sodium hydroxide buffer solution (pH 9.6) and use this solution as the standard solution. Perform the test with the sample solution and standard solution as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, using a mixture of boric acid-potassiu…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of 10z Phenobarbital ‌Powder, dissolve in a boric acid-potassium chloride-sodium hydroxide buffer solution (pH 9.6) to make exactly 100 mL. Pipet 5 mL of this solution, add a boric acid-potassium chlo-ride-sodium hydroxide buffer solution (pH 9.6) to make ex-actly 100 mL, and use this solution as the sample solution. Separately, weigh accurately about 20 mg of phenobarbital for assay, previously dried at 1059C for 2 hours, and add a boric acid-potassium chloride-sodium hydroxide buffer solu-tion (pH 9.6) to make exactly 100 mL. Pipet 5 mL of this so-lution, add a boric acid-potassium chloride-sodium hydrox-ide buffer solution (pH 9.6) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with the sample solution and standard solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, using a boric acid-potassium chloride-sodium hydroxide buffer solution (pH 9.6) as the blank, and determine the absorbances, AT and AS, at 240 nm. minute after starting the test, and filter through a membrane filter with a pore size not exceeding 0.45 mm. Discard not less than 10 mL of the first filtrate, pipet V mL of the subsequent filtrate, and add water to make exactly V? mL so that each mL contains about 33 mg of phenobarbital (C12H12N2O3). Pipet 5 mL of this solution, add exactly 10 mL of boric acid-potassium chloride-sodium hydroxide buffer solution (pH 9.6), and use this solution as the sample solution. Separately, weigh accurately about 17 mg of phenobarbital for assay, previously dried at 1059C for 2 hours, and dissolve in water to make exactly 100 mL. Pipet 5 mL of this solution, and add water to make exactly 25 mL. Pipet 5 mL of this solu-tion, add exactly 10 mL of boric acid-potassium chloride-sodium hydroxide buffer solution (pH 9.6), and use this so-lution as the standard solution. Determine the absorbances, AT and AS, at 240 nm of the sample solution and standard solution as directed under Ultra…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

copovidone
type: ChemicalDrugMonograph
pref label:
  en: Copovidone
  ja: コポビドン
monograph id: JP18-copovidone
publisher: JP
status: Official
version: 18
definition:
  en: Copovidone is a copolymer of 1-vinyl-2-pyrrolidone and vinyl acetate at the ratio by mass of 3:2. It contains not less than 35.
appearance:
  en: Copovidone occurs as a white to yellowish white powder. It is odorless or has a faint, characteristic odor. It is very soluble in methanol and in ethanol (95), and freely soluble in water. It is hygroscopic.◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Copovidone, previously dried, as directed in the potas-sium bromide disk method under Infrared Spectrophotome-try <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorp- mL, and use this solution as the standard solution. Measure exactly 0.5 mL each of the sample solution, standard solu-tion and water, transfer to separate 1-cm cells, add 2.5 mL of 0.05 mol/L pyrophosphate buffer solution (pH 9.0) and 0.2 mL of b-nicotinamide adenine dinucleotide TS to each of these cells, mix and stopper tightly. Allow to stand for 2 to 3 minutes at 22 ± 29C, and perform the test with these solu-tions as directed under Ultraviolet-visible Spectrophotome-try <2.24> using water as the control solution. Determine the absorbances, AT1, AS1 and AB1, of the subsequent solutions of the sample solution, the standard solution and water (blank) at 340 nm. Then, add 0.05 mL of aldehyde de-hydrogenase TS to each of the cells, stir, and stopper tightly. Allow to stand at 22 ± 29C for 5 minutes. Determine the ab-sorbances, AT2, AS2 and AB2, of these solutions in the same manner as above: the content of aldehyde is not more than 500 ppm. Content (ppm) of aldehydes [as acetaldehyde (CH3CHO)] ＝ C/M ×{(AT2 － AT1) － (AB2 － AB1)}/{(AS2 － AS1) － (AB2 － AB1)}× 100,000 M: Amount (g) of Copovidone taken, calculated on the dried basis C: Concentration (mg/mL) of acetaldehyde in the stand-ard solution, using 0.72 as conversion factor for acetal-dehyde ammonia trimer trihydrate to acetaldehyde 1-Vinyl-2-pyrrolidone and free vinyl acetate—Store the sample solution and the standard solution at 59C or below, and use within 8 hours. Weigh accurately about 0.25 g of Copovidone, dissolve in a mixture of water and aceto-nitrile (23:2) to make exactly 10 mL, and use this solution as the sample solution. Separately, dissolve 50 mg each of 1-vinyl-2-pyrrolidone and vinyl acetate in methanol to make exactly 100 mL. P…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Copovidone in 10 mL of water: the solution is clear or slightly opalescent and colorless to pale yellow, or pale red. CSa : Concentration ( mg/mL) of 1-vinyl-2-pyrrolidone in the standard solution (2) Heavy metals <1.07>—Ignite 2.0 g of Copovidone as directed under Residue on Ignition Test <2.44>, add 2 mL of hydrochloric acid to the residue, then proceed according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm).◇ Aldehydes—Weigh accurately about 1 g of Copovi-done, dissolve in 0.05 mol/L pyrophosphate buffer solution (pH 9.0) to make exactly 100 mL. Stopper, heat at 609C for 60 minutes, allow to cool to room temperature, and use this solution as the sample solution. Separately, dissolve 0.140 g of acetaldehyde ammonia trimer trihydrate in water to make exactly 200 mL. Pipet 1 mL of this solution, add 0.05 mol/L pyrophosphate buffer solution (pH 9.0) to make exactly 100 CSb: Concentration (mg/mL) of vinyl acetate in the stand- ard solution CT: Concentration (mg/mL) of Copovidone in the sample solution, calculated on the dried basis Operating conditions— Detector: An ultraviolet spectrophotometer (wavelength: 235 nm for 1-vinyl-2-pyrrolidone, 205 nm for vinyl acetate). Column: Two stainless steel columns, one is 4 mm in in-side diameter and 33 mm in length and the other is 4 mm in inside diameter and 250 mm in length, packed with oc-tadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter), and use them as the pre-column and the separation column, respectively. Column temperature: A constant temperature of about JP XVIII Official Monographs / Copovidone 813 409C. Mobile phase: A mixture of water and acetonitrile (23:2). Flow rate: 1.0 mL per minute (Retention times of 1-vinyl- pyrrolidone and vinyl acetate are about 17 and about 22 minutes, respectively). tion and standard solution as directed under Liquid Chroma-tog…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Vinyl acetate—Weigh accurately about 2 g of Copovidone, add exactly 25 mL of 0.5 mol/L potassium hy-droxide-ethanol VS and a few glass beads, heat under reflux for 30 min. Titrate immediately with 0.5 mol/L hydrochloric acid VS (indicator: 1 mL of phenolphthalein TS). Perform a blank determination in the same manner, and make any nec-essary correction. Amount (z) of vinyl acetate Description Cortisone Acetate occurs as white, crystals or crystalline powder. It is sparingly soluble in methanol, slightly soluble in ethanol (99.5), and practically insoluble in water. Melting point: about 2409C (with decomposition). It shows crystal polymorphism. Identification (1) To 2 mg of Cortisone Acetate add 2 mL ‌＝ 0.1 × 86.09 × 56.11 28.05 (n2 – n1) M of sulfuric acid, and allow to stand for a while: a yellowish green color is produced, and it gradually changes to yellow-orange. Examine the solution under ultraviolet light: the so- M: Amount (g) of Copovidone taken, calculated on the dried basis n1: Volume (mL) of 0.5 mol/L hydrochloric acid VS con-sumed in the test n2: Volume (mL) of 0.5 mol/L hydrochloric acid VS con-sumed in the blank test (2) Nitrogen—Weigh accurately about 0.1 g of Copovi-done, and place in a Kjeldahl flask. Add 5 g of a decomposi-tion accelerator (a powdered mixture of 33 g of potassium sulfate, 1 g of copper (II) sulfate pentahydrate and 1 g of titanium (IV) oxide), and wash down any adhering sample from the neck of the flask with a small amount of water. Add 7 mL of sulfuric acid allowing to flow down the inside wall of the flask. Heat the flask gradually until the solution has a clear, yellow-green color, and the inside wall of the flask is free from a carbonized material, and then heat for further 45 minutes. After cooling, add cautiously 20 mL of water, and connect the flask to the distillation apparatus pre-viously washed by passing steam through it. To the absorp-tion flask add 30 mL of a solution of boric acid (1 in 25), 3 drops of bromocresol …
type: PharmacopoeiaMonograph

corn-starch
type: ChemicalDrugMonograph
pref label:
  en: Corn Starch
  ja: トウモロコシデンプン
monograph id: JP18-corn-starch
publisher: JP
status: Official
version: 18
appearance:
  en: Corn Starch occurs as white to pale yellow-white, masses or powder. It is practically insoluble in water and in ethanol (99.5).◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Examined under a microscope <5.01>, using mixture of water and glycerin (1:1), Corn Starch ap-pears as either angular polyhedral granules of irregular sizes with diameters of 2 – 23 mm or as rounded or spheroidal granules of irregular sizes with diameters of 25 – 35 mm. The central hilum consists of a distinct cavity or two- to five-rayed cleft, and there are no concentric striations. Between orthogonally oriented polarizing plates or prisms, the starch granules show a distinct black cross intersecting at the hilum. To 1 g of Corn Starch add 50 mL of water, boil for 1 minute, and allow to cool: a thin, cloudy mucilage is formed. To 1 mL of the mucilage obtained in (2) add 0.05 mL of diluted iodine TS (1 in 10): an orange-red to deep blue color is formed and the color disappears by heating. pH <2.54> Put 5.0 g of Corn Starch in a non-metal vessel, add 25.0 mL of freshly boiled and cooled water, mix gently for 1 minute, and allow to stand for 15 minutes: the pH of the solution is between 4.0 and 7.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Iron—To 1.5 g of Corn Starch add 15 mL of 2 mol/L hydrochloric acid TS, mix, filter, and use the filtrate as the test solution. To 2.0 mL of Standard Iron Solution add water to make 20 mL, and use this solution as the con-trol solution. Put 10 mL each of the test solution and the control solution in test tubes, add 2 mL of a solution of citric acid (1 in 5) and 0.1 mL of mercapto acetic acid, and mix. Alkalize with ammonia solution (28) to litmus paper, add water to make 20 mL, and mix. Transfer 10 mL each of these solutions into test tubes, allow to stand for 5 minutes, ‌and compare the color of these solutions against a white background: the color of the test solution is not more intense than that of the control solution (not more than 10 ppm). Oxidizing substances—To 4.0 g of Corn Starch add ppm. Amount (ppm) of sulfur dioxide ＝ V/M × 1000 × 3.203 50.0 mL of water, shake for 5 minutes, and centrifuge. To 30.0 mL of the supernatant liquid add 1 mL of acetic acid (100) and 0.5 to 1.0 g of potassium iodide, shake, and allow to stand for 25 to 30 minutes at a dark place. Add 1 mL of starch TS, and titrate <2.50> with 0.002 mol/L sodium thio-sulfate VS until the color of the solution disappears. Per-form a blank determination in the same manner, and make any necessary correction: the volume of 0.002 mol/L sodium thiosulfate VS consumed is not more than 1.4 mL (not more than 20 ppm, calculated as hydrogen peroxide). Sulfur dioxide— Apparatus Use as shown in the following figure. A: Three-necked round-bottom flask (500 mL) B: Cylindrical dropping funnel (100 mL) C: Condenser D: Test tube E: Tap Procedure Introduce 150 mL of water into the three-necked round-bottom flask, close the tap of the cylin-drical dropping funnel, and pass carbon dioxide through the whole system at a rate of 100 ± 5 mL per minute. Pass cool-ing water through the condenser, and place 10 mL of hydro-gen peroxide-sodium hydroxide TS in the test tube. After 15 minutes, remove the funnel without i…
storage conditions:
  en: Containers—Well-closed contain-ers.◆
type: PharmacopoeiaMonograph

cortisone-acetate
type: ChemicalDrugMonograph
pref label:
  en: Cortisone Acetate
  ja: コルチゾン酢酸エステル
monograph id: JP18-cortisone-acetate
publisher: JP
status: Official
version: 18
molecular formula: C23H30O6
molecular weight: 402.48
cas number: 50-04-4
definition:
  en: Cortisone Acetate, when dried, contains not less than 97.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Related substances—Dissolve 25 mg of Cortisone Acetate in 10 mL of a mixture of acetonitrile, water and ace-tic acid (100) (70:30:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution add the mixture of acetonitrile, water and acetic acid (100) (70:30:1) to make exactly 100 mL, and use this solution as the standard solu-tion. Perform the test with exactly 15 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi-tions, and determine each peak area by the automatic in-tegration method: each peak area other than cortisone ace-tate obtained from the sample solution is not larger than 1/2 times the peak area of cortisone acetate from the standard solution, and the total area of the peaks other than cortisone acetate is not larger than 1.5 times the peak area of cortisone acetate from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase A: A mixture of water and acetonitrile (7:3). Mobile phase B: A mixture of acetonitrile and water (7:3). Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. 17,21-Dihydroxypregn-4-ene-3,11,20-trione 21-acetate [50-04-4] Cortisone Acetate, when dried, contains not less than 97.0z and not more than 102.0z of cortisone acetate (C23H30O6). ‌JP XVIII Official Monographs / Absorptive Cream 815‌ Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) 0 – 5 5 – 25 90 → 10 10 → 90 25 – 30 with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratios of the peak area of cortisone acetate to…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Dissolve about 10 mg each of Cortisone Acetate and Cortisone Acetate RS, previously dried and accurately weighed, in 50 mL of methanol, add exactly 5 mL each of the internal standard solution, then add methanol to make 100 mL, and use these solutions as the sample solution and the standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of cortisone acetate to that of the internal standard. Amount (mg) of cortisone acetate (C23H30O6) ＝ MS × QT/QS MS: Amount (mg) of Cortisone Acetate RS taken Internal standard solution—A solution of butyl parahy-droxybenzoate in methanol (3 in 5000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of water and acetonitrile (13:7). Flow rate: Adjust so that the retention time of cortisone acetate is about 12 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, cortisone acetate and the internal standard are eluted in this order with the resolution between these peaks being not less than 4. System repeatability: When the test is repeated 6 times Absorptive Cream
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

creosotum-ligni
type: ChemicalDrugMonograph
pref label:
  en: Creosotum Ligni
  ja: 木クレオソート
monograph id: JP18-creosotum-ligni
publisher: JP
status: Official
version: 18
appearance:
  en: Wood Creosote is a colorless or pale yellow, clear liquid. It has a characteristic odor. It is slightly soluble in water. It is miscible with methanol and with ethanol (99.5). Its saturated solution is acidic. It is highly refractive. It gradually changes in color by light or by air.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Use the sample solution obtained in the Assay as the sample solution. Separately, dissolve 0.1 g of phenol, p-cresol, guaiacol, and 2-methoxy-4-methylphenol in methanol respectively, to make 100 mL. To 10 mL of each solution add methanol to make 50 mL, and use these solu-tions as standard solution (1), standard solution (2), stan-dard solution (3) and standard solution (4). Perform the test with 10 mL each of the sample solution, standard solution (1), (2), (3) and (4) as directed under Liquid Chromato-graphy <2.01> according to the following conditions: the main peaks obtained with the sample solution show the same retention times with those obtained with the standard solu-tions (1), (2), (3) and (4). Operating conditions— Proceed as directed in the operating conditions in the Assay. Wood Creosote / Crude Drugs and Related Drugs Specific gravity <2.56> d 20: not less than 1.076.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Coal Creosote—Accurately measure 10 mL of Wood Creosote, add methanol to make exactly 20 mL, and use this solution as the sample solution. Separately, to 1 mg each of benzo[a]pyrene, benz[a]anthracene and dibenz[a,h]anthracene add a small quantity of ethyl acetate, if necessary, and add methanol to make 100 mL. To 1 mL of this solution add methanol to make 100 mL, and use this solution as the standard solution. Perform the test with ex-actly 1 mL each of the sample solution and standard solution as directed under Gas Chromatography <2.02> according to the following conditions: No peaks are detected with the sample solution for the retention times corresponding to benzo[a]pyrene, benz[a]anthracene and dibenz[a,h]anthra-cene of the standard solution. Change these conditions if any peak is detected for retention times that correspond to ben-zo[a]pyrene, benz[a]anthracene or dibenz[a,h]anthracene, to verify that such a peak does not belong to benzo[a]pyrene, benz[a]anthracene or dibenz[a,h]anthracene. Operating conditions— Detector: A mass spectrometer (EI). Monitored ions: Benz[a]anthracene: Molecular ion m/z 228, Fragment ion m/z 114 About 14 to 20 minutes Benzo[a]pyrene: Molecular ion m/z 252, Fragment ion m/z 125 About 20 to 25 minutes Dibenz[a,h]anthracene: Molecular ion m/z 278, Fragment ion m/z 139 About 25 to 30 minutes Column: A quartz tube 0.25 mm in inside diameter and 30 m in length, with internal coating 0.25 – 0.5 mm in thick-ness made of 5z diphenyl-95z dimethyl polysiloxane for gas chromatography. Column temperature: Inject sample at a constant tempera-ture in vicinity of 459C, then raise temperature to 2409C at the rate of 409C per minute, maintain the temperature at 2409C for 5 minutes, then raise temperature to 3009C at the rate of 49C per minute, then raise the temperature to 3209C at the rate of 109C per minute, then maintain temperature at 3209C for 3 minutes. Injection port temperature: A constant temperature in vicinity of 2509C. Interface te…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: To about 0.1 g of Wood Creosote, accurately weighed, add methanol to make exactly 50 mL. Pipet 10 mL of this solution add methanol to make exactly 50 mL, and use this solution as the sample solution. Separately, add methanol to about 30 mg of accurately measured guaiacol for assay to make exactly 50 mL. Pipet 10 mL of this solu-tion, add methanol to make exactly 50 mL, and use this solu-tion as the standard solution. Perform the test with 10 mL each of the sample solution and standard solution under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of guaiacol in each solution. Amount (mg) of guaiacol ＝ MS × AT/AS JP XVIII Crude Drugs and Related Drugs / Yokukansan Extract 2173 ‌MS: Amount (mg) of guaiacol for assay taken‌ Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 275 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Mixture of water and acetonitrile (4:1). Flow rate: Adjust so that the retention time of guaiacol is about 9 minutes. System suitability— System performance: Dissolve 2 mg each of guaiacol and phenol in methanol to make 10 mL. The procedure is run with conditions described above with 10 mL of this solution, the elution takes place in order of phenol then guaiacol, with the degree in separation of not less than 2.5. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of guaiacol is not more than 1.5z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.

cresol
type: ChemicalDrugMonograph
pref label:
  en: Cresol
  ja: クレゾール
monograph id: JP18-cresol
publisher: JP
status: Official
version: 18
molecular formula: C7H8O
molecular weight: 108.14
appearance:
  en: Cresol is a clear, colorless or yellow to yellow-brown liquid. It has a phenol-like odor. It is miscible with ethanol (95) and with diethyl ether. It is sparingly soluble in water. It dissolves in sodium hydroxide TS. A saturated solution of Cresol is neutral to bromocresol purple TS. It is a highly refractive liquid. It becomes dark brown by light or on aging.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 5 mL of a saturated solution of Cresol add 1 to 2 drops of dilute iron (III) chloride TS: a blue-purple color develops. Specific gravity <2.56> d 20: 1.032 – 1.041
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Hydrocarbons—Dissolve 1.0 mL of Cresol in 60 mL of water: the solution shows no more turbidity than that produced in the following control solution. Control solution: To 54 mL of water add 6.0 mL of 0.005 mol/L sulfuric acid VS and 1.0 mL of barium chloride TS, and after thorough shaking, allow to stand for 5 minutes. (2) Sulfur compounds—Transfer 20 mL of Cresol in a 100-mL conical flask, place a piece of moistened lead (II) acetate paper on the mouth of the flask, and warm for 5 minutes on a water bath: the lead (II) acetate paper may de-velop a yellow color, but neither a brown nor a dark tint. Distilling range <2.57> 196 – 2069C, not less than 90 volz.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.

croconazole-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Croconazole Hydrochloride
  ja: クロコナゾール塩酸塩
monograph id: JP18-croconazole-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C18H15ClN2O.HCl
molecular weight: 347.24
cas number: 77174-66-4
definition:
  en: Croconazole Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Croconazole Hydrochloride occurs as white to pale yellow-white, crystals or crystalline powder. It is very soluble in water, freely soluble in methanol, in ethanol (95) and in acetic acid (100), and practically insolu-ble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Croconazole Hydrochloride in methanol (1 in 20,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer- ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Croconazole Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolve 0.05 g of Croconazole Hydrochloride in 10 mL of water, add 2 mL of sodium hydroxide TS and 20 mL of diethyl ether, and shake. Wash the separated aqueous layer with two 10-mL portions of diethyl ether, and acidify the solution with 2 mL of dilute nitric acid: the solution re-sponds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Croconazole Hydrochloride according to Method 4, and per-form the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 50 mg of Croconazole Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solu-tion on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, hexane, methanol and ammonia solution (28) (30:15:5:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot and the spot of the starting point obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 609C, 4 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Croconazole Hy-drochloride, previously dried, dissolve in 10 mL of acetic acid (100), add 40 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS [indicator: 1 to 2 drops of a solution of malachite green oxalate in acetic acid (100) (1 in 100)] until the color of the solution changes from blue-green through green to yellow-green. Perform a blank determina-tion in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 34.72 mg of C18H15ClN2O.HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

crocus
type: ChemicalDrugMonograph
pref label:
  en: Crocus
  ja: サフラン
monograph id: JP18-crocus
publisher: JP
status: Official
version: 18
appearance:
  en: Thin cord-like stigma, externally dark yellow-red to red-brown, 1.5 – 3.5 cm in length, tripartite or sepa-rate; the end of partite part widened and the other end nar-rowed gradually. Odor, strong and characteristic; taste, bitter; colors the saliva yellow on chewing. Under a microscope <5.01>, when softened by immersion in water, the upper end has numerous tubular protrusions about 150 mm in length, with a small number of pollen grains.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Use the sample solution obtained in the Purity (1) as the sample solution. Perform the test with this solution as directed under Thin-layer Chromatography <2.03>. Spot 5 mL of the sample solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, methanol, water and acetic acid (100) (20:5:4:1) to a distance of about 10 cm, and air-dry the plate: three yellow spots appear at the Rf values of about 0.1, about 0.25 and about 0.4.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Synthetic dye—To 0.10 g of pulverized Saffron add 5 mL of methanol, shake for 10 minutes, centrifuge, and use the supernatant liquid as the sample solution. Perform the test with the sample solution as directed under Thin-layer Chromatography <2.03>. Spot 5 mL of the sample solution on a plate of silica gel for thin-layer chromatography. De-velop the plate with a mixture of ethyl acetate, methanol, water and acetic acid (100) (20:5:4:1) to a distance of about 10 cm, and air-dry the plate: any spot other than yellow spots does not appear upper in position than a yellow spot at an Rf value of about 0.4 and any yellow spot does not ap-pear between yellow spots at Rf values of about 0.25 and about 0.4. Spray evenly diluted sulfuric acid on the plate, and heat the plate at 1059C for 10 minutes: any clear yellow spot does not appear at an Rf value of less than 0.1, and any orange spot does not appear between blue-purple spots at Rf values of about 0.1 and about 0.25. Glycerol, sugar or honey—Saffron has no sweet taste. Press it between two pieces of paper: no spot is left on the paper. Yellow style—When perform the test of foreign matter <5.01>, the yellow style in Saffron does not exceed 10.0z. Loss on drying <5.01> Not more than 12.0z (6 hours). Total ash <5.01> Not more than 7.5z. Content of the active principle Crocin—Dry Saffron in a desiccator (silica gel) for 24 hours, and powder. To exactly 0.100 g of the powder add 150 mL of warm water, warm the mixture between 609C and 709C for 30 minutes with fre-quent shaking, cool, and filter. Pipet 1 mL of the filtrate, add water to make exactly 10 mL, and use this solution as the sample solution. Separately, dissolve exactly 98 mg of carbazochrome sodium sulfonate trihydrate in water to make exactly 100 mL. Pipet 5 mL of this solution, add water to make exactly 100 mL, and use this solution as the stand-ard solution. Determine the absorbances of the sample solu-tion and standard solution at 438 nm as directed under Ul-t…
storage conditions:
  en: Containers—Well-closed contain-ers.

crospovidone
type: ChemicalDrugMonograph
pref label:
  en: Crospovidone
  ja: クロスポビドン
monograph id: JP18-crospovidone
publisher: JP
status: Official
version: 18
definition:
  en: Crospovidone is a cross-linked polymer of 1-vinyl-2-pyrrolidone. It contains not less than 11.
appearance:
  en: Crospovidone occurs as a white to pale yel-low-powder. It is practically insoluble in water, in methanol and in ethanol (99.5). It is hygroscopic.◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Suspend 1 g of Crospovidone in 10 mL of water, add 0.1 mL of iodine TS, shake for 30 seconds, then add 1 mL of starch TS, and shake: a blue color is not produced within 30 seconds. (2) When add 0.1 g of Crospovidone to 10 mL of water, shake to suspend, and allow the suspension to stand, a clear liquid is not produced within 15 minutes. Particle size Weigh accurately about 20 g of Crospovidone, place in a 1000-mL conical flask, add 500 mL of water, shake for 30 minutes, and pour onto an accurately tared No. 235 (63 mm) sieve, previously washed with hot water and dried at 1059C for a night, and wash the residue with water until the passing water is clear. Dry the residue together with the sieve in a drying machine at 1059C for 5 hours without air-circulation. After cooling down in a desiccator for 30 minutes, weigh the mass of the residue with sieve, and calcu-late the amount of the residue on the sieve by the following equation: Type A is more than 15z, and type B is not more than 15z. Amount (z) of the residue of Crospovidone on No. 235 (63 mm) sieve ＝ (M1 － M3)/M2 × 100 M1: The mass (g) of the residue with sieve after 5 hours drying M2: Amount (g) of Crospovidone taken, calculated on the dried basis M3: Mass (g) of the sieve
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: ◆(1) Heavy metals <1.07>—Proceed with 2.0 g of Crospovidone according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm).◆ Water-soluble substances—Place 25.0 g of Crospovi-done in a 400-mL beaker, add 200 mL of water, and stir for 1 hour. Transfer the suspension to a 250-mL volumetric flask, rinsing with water, and dilute to volume with water. Allow the bulk of the solids to settle. Filter about 100 mL of the almost clear supernatant liquid through a 0.45 mm mem-brane filter, protected by superimposing a 3 mm membrane filter. Transfer exactly 50 mL of the clear filtrate to a tared 100-mL beaker, evaporate to dryness and dry at 105 – 1109C for 3 hours: the mass of the residue is not more than 75 mg. 1-Vinyl-2-pyrrolidone—To 1.250 g of Crospovidone add exactly 50 mL of methanol, and shake for 60 minutes. Leave bulk to settle, filter through a 0.2 mm membrane filter, and use the filtrate as the sample solution. Separately, dis-solve 50 mg of 1-vinyl-2-pyrrolidone in methanol to make exactly 100 mL. Pipet 1 mL of this solution, and add metha-nol to make exactly 100 mL. To exactly 5 mL of this solution add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 50 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions: the peak area of 1-vinyl-2-pyrrolidone obtained from the sample solution is not larger than that from the standard solution (not more than 10 ppm). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 235 nm). Column: Two stainless steel columns, one is 4 mm in in-side diameter and 25 mm in length and the other is 4 mm in inside diameter and 250 mm in length, they are packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter), and used them as the pre-column and the separat…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g of Crospovidone, place in a Kjeldahl flask, add 5 g of a decomposition acceler-ator (a powdered mixture of 33 g of potassium sulfate, 1 g of copper (II) sulfate pentahydrate and 1 g of titanium (IV) oxide) and 3 glass beads. Wash any adhering particles from the neck into the flask with a small quantity of water. Add 7 mL of sulfuric acid, allowing it to run down the inside wall of the flask. Gradually heat the flask until the solution has a clear, yellowish-green color, and the inside wall of the flask is free from carbonized material, and then heat for a further 45 minutes. After cooling, cautiously add 20 mL of water, and connect the flask to the distillation apparatus previously washed by passing steam through it. To the absorption flask add 30 mL of a solution of boric acid (1 in 25), 3 drops of bromocresol green-methyl red TS and sufficient water to im-merse the lower end of the condenser tube. Add 30 mL of a solution of sodium hydroxide (21 in 50) through a funnel, cautiously rinse the funnel with 10 mL of water, immediately close the clamp attached to the rubber tube, then start the distillation with steam to obtain 80 – 100 mL of distillate. Remove the absorption flask from the lower end of the con-denser tube, rinsing the end part with a small quantity of water, and titrate <2.50> the distillate with 0.025 mol/L sul-furic acid VS until the color of the solution changes from green through pale grayish blue to pale grayish red-purple. Carry out a blank determination in the same manner, and make any necessary correction. Each mL of 0.025 mol/L sulfuric acid VS ＝ 0.7003 mg of N
storage conditions:
  en: Containers—Tight containers.

cyanamide
type: ChemicalDrugMonograph
pref label:
  en: Cyanamide
  ja: シアナミド
monograph id: JP18-cyanamide
publisher: JP
status: Official
version: 18
molecular formula: CH2N2
molecular weight: 42.04
definition:
  en: Cyanamide contains not less than 97.
appearance:
  en: Cyanamide occurs as white, crystals or crystal-line powder. It is very soluble in water, in methanol, in ethanol (99.5) and in acetone. The pH of a solution of 1.0 g of Cyanamide in 100 mL of water is between 5.0 and 6.5. It is hygroscopic. Melting point: about 469C
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of a solution of Cyanamide (1 in 100) add 1 mL of potassium 1,2-naphthoquinone-4- sulfonate TS and 0.2 mL of sodium hydroxide TS: a deep red color develops. (2) Drop one or two drops of a solution of Cyanamide in acetone (1 in 100) onto a potassium bromide disk prepared as directed in the potassium bromide disk method under In-frared Spectrophotometry <2.25>, and air-dry the disk. De-termine the infrared absorption spectrum of the disk as di-rected in the film method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec-trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Cyanamide in 10 mL of water: the solution is clear and colorless. (2) Heavy metals <1.07>—Proceed with 2.0 g of Cyanamide according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Water <2.48> Not more than 1.0z (1 g, volumetric titra-tion, direct titration). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 1 g of Cyanamide, and dis-solve in water to make exactly 250 mL. Pipet 15 mL of this solution, add 2 to 3 drops of dilute nitric acid, 10 mL of am-monia TS and exactly 50 mL of 0.1 mol/L silver nitrate VS, and allow to stand for 15 minutes with occasional shaking. Add water to make exactly 100 mL, filter, discard the first 20 mL of the filtrate, and pipet 50 mL of the subsequent filtrate. After neutralizing this solution with dilute nitric acid, add 3 mL of dilute nitric acid, and titrate <2.50> the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ammonium iron (III) sulfate TS). Perform a blank determination in the same manner. Each mL of 0.1 mol/L silver nitrate VS ＝ 2.102 mg of CH2N2
storage conditions:
  en: Containers—Tight containers. Storage—In a cold place.
type: PharmacopoeiaMonograph

cyclopentolate-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Cyclopentolate Hydrochloride
  ja: シクロペントラート塩酸塩
monograph id: JP18-cyclopentolate-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C17H25NO3.HCl
molecular weight: 327.85
appearance:
  en: Cyclopentolate Hydrochloride occurs as a white crystalline powder. It is odorless, or has a characteris-tic odor. It is very soluble in water, freely soluble in ethanol (95), in acetic acid (100) and in chloroform, sparingly soluble in ace-tic anhydride, and practically insoluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of a solution of Cyclopento-late Hydrochloride (1 in 100) add 1 mL of Reinecke salt TS: a light red precipitate is formed. Dissolve 0.2 g of Cyclopentolate Hydrochloride in 2 mL of water, add 2 mL of sodium hydroxide TS, and boil for 1 minute. After cooling, add 2 drops of nitric acid: a phenylacetic acid-like odor is perceptible. Determine the infrared absorption spectrum of Cy-clopentolate Hydrochloride, previously dried, as directed in the potassium chloride disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Cyclopentolate Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 0.20 g of Cyclopentolate Hydrochlo-ride in 20 mL of water: the pH of this solution is between 4.5 and 5.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Cyclopentolate Hydrochloride in 10 mL of water: the so-lution is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Cy- clopentolate Hydrochloride according to Method 1, and per- 63 88 14 14 form the test. Prepare the control solution with 2.0 mL of use this solution as the sample solution. Separately, weigh accurately about 20 mg of Cyanocobalamin RS (previously determine the loss on drying <2.41> under the same condi-tions as Cyanocobalamin), add water to make exactly 1000 mL, and use this solution as the standard solution. Then, proceed as directed in the Assay under Cyanocobalamin. Amount (mg) of cyanocobalamin (C63H88CoN14O14P) ＝ MS × AT/AS × 1/10 Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.20 g of Cyclopento-late Hydrochloride in 10 mL of chloroform, and use this so-lution as the sample solution. Pipet 1 mL of the sample solu-tion, and add chloroform to make exactly 20 mL. Pipet 1 mL of this solution, add chloroform to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chro- ‌822‌ matography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of 2-propanol, n-butyl acetate, water and ammonia solution (28) (100:60:23:17) to a distance of about 10 cm, and air-dry the plate. Spray evenly a solution of sulfuric acid in ethanol (99.5) (1 in 10) on the plate, and heat the plate at 1209C for 30 minutes. Examine under ultraviolet light (main wave-length: 254 nm): the spots other than the principal spot ob-tained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.05z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Cyclopentolate Hy-drochloride, previously dried, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (4:1), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue-green to yel-low-green (indicator: 2 drops of crystal violet TS). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 32.79 mg of C17H25NO3.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

cyclophosphamide-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Cyclophosphamide Hydrate
  ja: シクロホスファミド水和物
monograph id: JP18-cyclophosphamide-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C7H15Cl2N2O2P.H2O
molecular weight: 279.1
definition:
  en: Cyclophosphamide Hydrate contains not less than 97.
appearance:
  en: Cyclophosphamide Hydrate occurs as white, crystals or crystalline powder. It is odorless. It is very soluble in acetic acid (100), freely soluble in ethanol (95), in acetic anhydride and in chloroform, and soluble in water and in diethyl ether. Melting point: 45 – 539C
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.1 g of Cyclophosphamide Hydrate in 10 mL of water, and add 5 mL of silver nitrate TS: no precipitate is produced. Then boil this solution: a white precipitate is produced. Collect the precipitate, and add dilute nitric acid to a portion of this precipitate: it does not dissolve. Add excess ammonia TS to another portion of the precipitate: it dissolves. (2) Add 1 mL of diluted sulfuric acid (1 in 25) to 0.02 g of Cyclophosphamide Hydrate, and heat until white fumes are evolved. After cooling, add 5 mL of water, and shake. Neutralize with ammonia TS, then acidify with dilute nitric acid: this solution responds to Qualitative Tests <1.09> (2) for phosphate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.20 g of Cyclophosphamide Hydrate in 10 mL of water: the solu-tion is clear and colorless. Chloride <1.03>—Perform the test with 0.40 g of Cy- clophosphamide Hydrate at a temperature not exceeding 209C. Prepare the control solution with 0.40 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.036z). Heavy metals <1.07>—Proceed with 1.0 g of Cy- clophosphamide Hydrate according to Method 1, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Water <2.48> 5.5 – 7.0z (0.5 g, volumetric titration, direct titration).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Cyclophosphamide Hydrate, add 15 mL of hydrogen chloride-ethanol TS, and heat in a water bath under a reflux condenser for 3.5 hours while protecting from moisture. Distil the ethanol under reduced pressure. Dissolve the residue in 40 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid-dioxane VS (indicator: 2 drops of crystal violet TS) until the color of the solution changes from blue through green to yellow. Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid-dioxane VS ＝ 13.96 mg of C7H15Cl2N2O2P.H2O
storage conditions:
  en: Containers—Tight containers. Storage—Not exceeding 309C.
type: PharmacopoeiaMonograph

cyproheptadine-hydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Cyproheptadine Hydrochloride Hydrate
  ja: シプロヘプタジン塩酸塩水和物
monograph id: JP18-cyproheptadine-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: N.HCl
molecular weight: 323.86
definition:
  en: Cyproheptadine Hydrochloride Hydrate, when dried, contains not less than 98.
appearance:
  en: Cyproheptadine Hydrochloride Hydrate oc-curs as a white to pale yellow crystalline powder. It is odor-less, and has a slightly bitter taste. It is freely soluble in methanol and in acetic acid (100), soluble in chloroform, sparingly soluble in ethanol (95), slightly soluble in water, and practically insoluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.1 g of Cyproheptadine Hy-drochloride Hydrate in 10 mL of methanol, apply 1 drop of this solution on filter paper, air-dry, and examine under ul-traviolet light (main wavelength: 254 nm): the solution shows a pale blue fluorescence. Weigh 0.1 g of Cyproheptadine Hydrochloride Hy-drate, transfer to a separator, dissolve in 5 mL of chlo-roform, add 4 mL of water and 1 mL of sodium carbonate TS, and shake. Transfer the chloroform layer to another separator, and wash with 4 mL of water by shaking well. Filter the chloroform layer through absorbent cotton moistened previously with chloroform, and evaporate the filtrate to dryness. Dissolve the residue in 8 mL of dilute ethanol by warming at 659C. Rub the inner wall of the con-tainer with a glass rod while cooling until crystallization be-gins, and allow to stand for 30 minutes. Collect the crystals, and dry at 809C for 2 hours: the crystals melt <2.60> between 1119C and 1159C. Determine the absorption spectrum of a solution of Cyproheptadine Hydrochloride Hydrate in ethanol (95) (1 in 100,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. A saturated solution of Cyproheptadine Hydrochlo-ride Hydrate responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Acidity—Dissolve 2.0 g of Cyproheptadine Hydrochloride Hydrate in 25 mL of methanol, and add 1 drop of methyl red TS and 0.30 mL of 0.1 mol/L sodium hy-droxide VS: a yellow color develops. (2) Heavy metals <1.07>—Proceed with 1.0 g of Cypro- heptadine Hydrochloride Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Loss on drying <2.41> 7.0 – 9.0z (1 g, in vacuum at a pres- ‌JP XVIII Official Monographs / L-Cysteine 825 sure not exceeding 0.67 kPa, 1009C, 5 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform the test according to the Cylinder-plate method as directed under Microbial Assay for Antibiotics <4.02> according to the following conditions. Test organism—Bacillus subtilis ATCC 6633 Culture medium—Use the medium i in 1) Medium for test organism [5] under (1) Agar media for seed and base layer. Adjust the pH of the medium so that it will be 6.0 to 6.1 after sterilization. Standard solutions—Weigh accurately an amount of Cycloserine RS, previously dried at 609C for 3 hours under reduced pressure of not exceeding 0.67 kPa, equivalent to about 40 mg (potency), dissolve in water to make exactly 100 mL, and use this solution as the standard stock solution. Keep the standard stock solution at 59C or below and use within 24 hours. Take exactly a suitable amount of the standard stock solution before use, and add phosphate buffer solution (pH 6.0) to make solutions so that each mL contains 100 mg (potency) and 50 mg (potency), and use these solutions as the high concentration standard solution and the low concentration standard solution, respectively. Sample solutions—Weigh accurately an amount of Cycloserine equivalent to about 40 mg (potency), dissolve in water to make exactly 100 mL. Take exactly a suitable amount of this solution, add phosphate buffer solution (pH 6.0) to make solutions so that each mL contains 100 mg (po-tency) and 50 mg (potency), and use these solutions as the high concentration sample solution and the low concentra-tion sample solution, respectively.
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

cytarabine
type: ChemicalDrugMonograph
pref label:
  en: Cytarabine
  ja: シタラビン
monograph id: JP18-cytarabine
publisher: JP
status: Official
version: 18
molecular formula: C9H13N3O5
molecular weight: 243.22
definition:
  en: Cytarabine, when dried, contains not less than 98.
appearance:
  en: Cytarabine occurs as white, crystals or crystal-line powder. It is freely soluble in water, soluble in acetic acid (100), and very slightly soluble in ethanol (99.5). It dissolves in 0.1 mol/L hydrochloric acid TS. Melting point: about 2149C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Cytarabine in 0.1 mol/L hydrochloric acid TS (1 in 100,000) as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Cytarabine as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋154 – ＋1609(after drying, 0.1 g, water, 10 mL, 100 mm). pH <2.54> Dissolve 0.20 g of Cytarabine in 20 mL of water: the pH of this solution is between 6.5 and 8.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Cytarabine in 10 mL of water: the solution is clear and colorless. Chloride <1.03>—Perform the test with 1.0 g of Cytarabine. Prepare the control solution with 0.25 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.009z). Heavy metals <1.07>—Proceed with 1.0 g of Cytara-bine according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.10 g of Cytarabine in 10 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make ex-actly 200 mL, and use this solution as the standard solution (1). Pipet 10 mL of the standard solution (1), add water to make exactly 25 mL and use this solution as the standard so-lution (2). Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solutions (1) and (2) on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with 1-butanol saturated with water to a distance of about 12 cm, and air-dry the ‌828‌‌ plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution (1), and the number of them which are more intense than the spot from the standard solution (2) is not more than two. Spray evenly acidic potassium perman-ganate TS on the plate: any spot other than the principal spot does not appear. Loss on drying <2.41> Not more than 1.0z (1 g, in vacu-um, silica gel, 4 hours). Residue on ignition <2.44> Not more than 0.5z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Cytarabine, previ-ously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.05 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.05 mol/L perchloric acid VS ＝ 12.16 mg of C9H13N3O5
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

d-camphor
type: ChemicalDrugMonograph
pref label:
  en: d-Camphor
  ja: d-カンフル
monograph id: JP18-d-camphor
publisher: JP
status: Official
version: 18
molecular formula: C10H16O
molecular weight: 152.23
definition:
  en: d-Camphor contains not less than 96.
appearance:
  en: d-Camphor occurs as colorless or white, trans-lucent crystals, crystalline powder or masses. It has a charac-teristic, agreeable odor, and a slightly bitter taste, followed by a pleasant, cooling sensation. It is freely soluble in ethanol (95), in diethyl ether and in carbon disulfide, and slightly soluble in water. It slowly volatilizes at room temperature.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Dissolve 0.1 g of d-Camphor in 2 mL of methanol, add 1 mL of 2,4-dinitrophenylhydradine TS, and heat for 5 minutes on a water bath: an orange-red precipitate is formed. D Optical rotation <2.49> [a]20: ＋41.0 – ＋43.09(5 g, ethanol System repeatability: When the test is repeated 6 times with 2 mL of the standard solution under the above operating conditions, the relative standard deviation of the ratios of the peak area of d-camphor to that of the internal standard is not more than 1.0z.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g each of d-Camphor and d-Camphor RS, add exactly 5 mL each of the internal standard solution, dissolve in ethanol (99.5) to make 100 mL, and use these solutions as the sample solution and the standard solution. Perform the test with 2 mL each of the sample solution and standard solution as directed under Gas Chromatography <2.02> according to the following condi-tions, and calculate the ratios, QT and QS, of the peak area of d-camphor to that of the internal standard. Amount (mg) of d-camphor (C10H16O) ＝ MS × QT/QS MS: Amount (mg) of d-Camphor RS taken Internal standard solution—A solution of methyl salicylate in ethanol (99.5) (1 in 25). Operating conditions— Detector: A hydrogen flame-ionization detector. Column: A glass column 3 mm in inside diameter and 3 m in length, which is packed with 10z of polyethylene glycol 20 M for gas chromatography supported on 180 to 250 mm mesh silanized siliceous earth for gas chromatography. Column temperature: A constant temperature of about 1609C. Carrier gas: Nitrogen. Flow rate: Adjust so that the retention time of d-camphor is about 6 minutes. System suitability— System performance: When the procedure is run with 2 mL of the standard solution under the above operating condi-tions, d-camphor and the internal standard are eluted in this phor (C 10H16 O). order with the resolution between these peaks being not less than 7. Description d-Camphor occurs as colorless or white, trans-lucent crystals, crystalline powder or masses. It has a charac-teristic, agreeable odor, and a slightly bitter taste, followed by a pleasant, cooling sensation. It is freely soluble in ethanol (95), in diethyl ether and in carbon disulfide, and slightly soluble in water. It slowly volatilizes at room temperature. Identification Dissolve 0.1 g of d-Camphor in 2 mL of methanol, add 1 mL of 2,4-dinitrophenylhydradine TS, and heat for 5 minutes on a water bath: an orange-red precipitate is formed. D Optical rotation <2.49> [a]20:…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

d-chlorpheniramine-maleate
type: ChemicalDrugMonograph
pref label:
  en: d-Chlorpheniramine Maleate
  ja: d-クロルフェニラミンマレイン酸塩
monograph id: JP18-d-chlorpheniramine-maleate
publisher: JP
status: Official
version: 18
cas number: 2438-32-6
definition:
  en: d-Chlorpheniramine Maleate, when dried, contains not less than 99.
appearance:
  en: d-Chlorpheniramine Maleate occurs as a white crystalline powder. It is very soluble in water, in methanol and in acetic acid (100), and freely soluble in N,N-dimethylformamide and in ethanol (99.5). It dissolves in dilute hydrochloric acid.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of d-Chlorpheniramine Maleate in 0.1 mol/L hy-drochloric acid TS (3 in 100,000) as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the ‌744 spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of d-Chlorpheniramine Maleate, previously dried, as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Dissolve 0.10 g of d-Chlorpheniramine Maleate in 5 mL of methanol, and use this solution as the sample solu-tion. Separately, dissolve 56 mg of maleic acid in 10 mL of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of diethyl ether, methanol, acetic acid (100) and water (70:20:7:3) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): a spot among two of the spots obtained with the sample solution shows the same intense to the spot obtained with the standard solution, and its Rf value is about 0.4. D Optical rotation <2.49> [a]20: ＋39.5 – ＋43.09(after dry-ing, 0.5 g, N,N-dimethylformamide, 10 mL, 100 mm). pH <2.54> Dissolve 1.0 g of d-Chlorpheniramine Maleate in 100 mL of freshly boiled and cooled water: the pH of this so-lution is between 4.0 and 5.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of d-Chlorpheniramine Maleate in 50 mL of water: the solu-tion is clear and colorless. Heavy metals <1.07>—Proceed with l.0 g of d-Chlor- pheniramine Maleate according to Method 4 and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.10 g of d-Chlor-pheniramine Maleate in 100 mL of the mobile phase, and use this solution as the sample solution. Pipet 3 mL of the sam-ple solution, add the mobile phase to make exactly 100 mL. Pipet 2 mL of this solution, add the mobile phase to make exactly 20 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solu-tion and standard solution as directed under Liquid Chroma-tography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the area of the peak other than maleic acid and d-chlorpheniramine obtained from the sample solution is not larger than 2/3 times the peak area of d-chlorpheniramine from the standard solution, and the total area of these peaks is not larger than the peak area of d-chlorpheniramine from the standard solution. Time span of measurement: About 4 times as long as the retention time of d-chlorpheniramine, beginning after the solvent peak. System suitability— Test for required detectability: To exactly 2.5 mL of the standard solution add the mobile phase to make exactly 25 mL. Confirm that the peak area of d-chlorpheniramine ob-tained with 20 mL of this solution is equivalent to 7 to 13z of that with 20 mL of the standard solution. System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of d-chlorpheniramine are not less than 4000 and not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 20 …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately the mass of not less than 20 Chlor-pheniramine Maleate Tablets, and powder. Weigh accurately a portion of the powder, equivalent to about 4 mg of chlor-pheniramine maleate (C16H19ClN2.C4H4O4), add 70 mL of the internal standard solution, shake for 15 minutes, then add the internal standard solution to make exactly 100 mL, filter through a membrane filter with a pore size not exceed-ing 0.5 mm, and use this solution as the sample solution. Separately, weigh accurately about 20 mg of Chlorphenira-mine Maleate RS, previously dried at 1059C for 3 hours, and add the internal standard to make exactly 100 mL. Pipet 20 mL of this solution, add the internal standard solution to make exactly 100 mL, and use this solution as the standard solution. Perform the test with 30 mL each of the sample so-lution and standard solution as directed under Liquid Chro-matography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of (3S )-3-(4-Chlorophenyl)-N,N-dimethyl-3-pyridin-2-ylpropylamine monomaleate [2438-32-6] d-Chlorpheniramine Maleate, when dried, contains not less than 99.0z and not more than 101.0z of d-chlorpheniramine maleate (C16H19ClN2.C4H4O4). Description d-Chlorpheniramine Maleate occurs as a white crystalline powder. It is very soluble in water, in methanol and in acetic acid (100), and freely soluble in N,N-dimethylformamide and in ethanol (99.5). It dissolves in dilute hydrochloric acid. Identification (1) Determine the absorption spectrum of a solution of d-Chlorpheniramine Maleate in 0.1 mol/L hy-drochloric acid TS (3 in 100,000) as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the ‌744 spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of d-Chlorpheniramine Maleate, previously dried, as directed in the paste method under Infrared Spectrophotometry <2.25>, and compare…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

d-mannitol
type: ChemicalDrugMonograph
pref label:
  en: D-Mannitol
  ja: D-マンニトール
monograph id: JP18-d-mannitol
publisher: JP
status: Official
version: 18
molecular formula: C6H14O6
molecular weight: 182.17
cas number: 69-65-8
definition:
  en: D-Mannitol [69-65-8] MS: Amount (mg) of Manidipine Hydrochloride RS taken C: Labeled amount (mg) of manidipine hydrochloride (C35H38N4O6.2HCl) in 1 tablet Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 228 nm). Column: A stainless steel column 4.0 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of acetonitrile and a solution of potassium dihydrogen phosphate (681 in 100,000) (3:2). Flow rate: Adjust so that the retention time of manidipine is about 6 minutes. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of manidipine are not less than 1500 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times This monograph is harmonized with the European Phar-macopoeia and the U.S. Pharmacopeia. The parts of the text that are not harmonized are marked with symbols (◆ ◆). Information on the harmonization with the European Pharmacopoeia and the U.S. Pharmacopeia is available on the website of the Pharmaceuticals and Medical Devices Agency. D-Mannitol contains not less than 97.
appearance:
  en: D-Mannitol occurs as white, crystals, powder or grain. It has a sweet taste with a cold sensation. It is freely soluble in water, and practically insoluble in ethanol (99.5). It dissolves in sodium hydroxide TS. It shows crystal polymorphism.◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of D-Mannitol as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of D-Mannitol RS: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, put 25 mg each of D-Mannitol and D-Mannitol RS in glass vessels, dissolve in 0.25 mL of water without heating, dry them in a 600 – 700 W microwave oven for 20 minutes or in a drying chamber at 1009C for 1 hour, then further dry by gradual reducing pres-sure, and perform the same test as above with so obtained non-sticky white to pale yellow powders: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 5.0 g of D-Mannitol in water to make 50 mL, and use this solution as the test solution. Perform the test with the test solution as directed under Turbidity Measurement <2.61>: the solution is clear. Perform the test with the test solution according to Method 2 under Methods for Color Matching <2.65>: the so-lution is colorless. (2) Heavy metals <1.07>—Proceed with 5.0 g of D-Man- nitol according to Method 1, and perform the test. Prepare the control solution with 2.5 mL of Standard Lead Solution (not more than 5 ppm)◆. Nickel—Shake 10.0 g of D-Mannitol with 30 mL of 2 mol/L acetic acid TS, and add water to make exactly 100 mL. Add 2.0 mL of a saturated solution of ammonium pyrrolidinedithiocarbamate (about 10 g/L) and 10.0 mL of water-saturated 4-methyl-2-pentanone, and shake for 30 sec-onds without exposure to light. Allow the layers to separate, and use the 4-methyl-2-pentanone layer as the sample solu-tion. Separately, put 10.0 g each of D-Mannitol in three ves-sels, add 30 mL of 2 mol/L acetic acid TS to them, shake, add a suitable amount of water and exactly 0.5 mL, 1.0 mL and 1.5 mL respectively of Standard Nickel Solution for Atomic Absorption Spectrophotometry, and add water to make them exactly 100 mL. Then, proceed in the same man-ner as the sample solution, and use so obtained three 4-methyl-2-pentanone layers as the standard solutions. Addi-tionally, prepare a 4-methyl-2-pentanone layer by proceeding in the same manner as the sample solution without using D-Mannitol, and use this layer as the blank solution. Perform the test with the sample solution and standard solutions as directed in the standard addition method under Atomic Ab-sorption Spectrophotometry <2.23> according to the follow-ing conditions. Set the zero of the instrument using the blank solution, and between each measurement, rinse with water and ascertain that the readings return to zero with the blank solution: amount of nickel is not more than 1 …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g each of D-Mannitol and D-Mannitol RS (separately determine the loss on drying <2.41> under the same conditions as D-Mannitol), dissolve separately in water to make exactly 10 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of D-mannitol in each solution. Amount (g) of D-mannitol (C6H14O6) ＝ MS × AT/AS MS: Amount (g) of D-Mannitol RS taken, calculated on the dried basis Operating conditions— ‌Detector: A differential refractometer maintained at a constant temperature (409C for example).‌ Column: A stainless steel column 7.8 mm in inside diame-ter and 30 cm in length, packed with strongly acidic ion-exchange resin for liquid chromatography (calcium type) composed with a sulfonated polystyrene cross-linked with 8z of divinylbenzene (9 mm in particle diameter). Column temperature: 85 ± 29C. Mobile phase: water. Flow rate: 0.5 mL per minute (the retention time of D-mannitol is about 20 minutes). System suitability— System performance: Dissolve 0.25 g each of D-Mannitol and D-sorbitol in water to make 10 mL, and use this solution as the solution for system suitability test (1). Separately, dis-solve 0.5 g each of maltitol and isomalt in water to make 100 mL. To 2 mL of this solution add water to make 10 mL, and in 5), no precipitate is produced. pH <2.54> 4.5 – 7.0 Bacterial endotoxins <4.01> Less than 0.50 EU/mL. Extractable volume <6.05> It meets the requirement. Foreign insoluble matter <6.06> Perform the test according to Method 1: it meets the requirement. Insoluble particulate matter <6.07> It meets the require-ment. Sterility <4.06> Perform the test according to the Mem-brane filtration method: it meets the requirement. Assay Measure exactly a volume of D-Mannitol Injection, equivalen…
storage conditions:
  en: Containers—Well-closed contain-ers.◆
type: PharmacopoeiaMonograph

d-sorbitol
type: ChemicalDrugMonograph
pref label:
  en: D-Sorbitol
  ja: D-ソルビトール
monograph id: JP18-d-sorbitol
publisher: JP
status: Official
version: 18
molecular formula: C6H14O6
molecular weight: 182.17
cas number: 50-70-4
definition:
  en: D-Sorbitol, when dried, contains not less than 97.
appearance:
  en: D-Sorbitol occurs as white, granules, powder, or crystalline masses. It is odorless, and has a sweet taste with a cold sensation. It is very soluble in water, sparingly soluble in ethanol (95), and practically insoluble in diethyl ether. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of a solution of D-Sorbitol (7 in 10) add 2 mL of iron (II) sulfate TS and 1 mL of a solu-tion of sodium hydroxide (1 in 5): a blue-green color devel-ops, but no turbidity is produced. Shake thoroughly 1 mL of a solution of D-Sorbitol (1 in 20) with 1 mL of a freshly prepared solution of catechol (1 in 10), add rapidly 2 mL of sulfuric acid, and shake: a reddish purple to red-purple color immediately develops. Boil 0.5 g of D-Sorbitol with 10 mL of acetic anhy-dride and 1 mL of pyridine under a reflux condenser for 10 minutes, cool, shake with 25 mL of water, and allow to stand in a cold place. Transfer the solution to a separator, extract with 30 mL of chloroform, and evaporate the extract on a water bath. Add 80 mL of water to the oily residue, heat for 10 minutes on a water bath, then filter the hot mix-ture. After cooling, collect the produced precipitate through a glass filter (G3), wash with water, recrystallize once from ethanol (95), and dry in a desiccator (in vacuum, silica gel) for 4 hours: the precipitate melts <2.60> between 979C and 1019C.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution, and acidity or alkalinity—Dissolve 5 g of D-Sorbitol in 20 mL of water by warming with shaking: the solution is clear, colorless, and neutral. Chloride <1.03>—Perform the test with 2.0 g of D- Sorbitol. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.005z). Sulfate <1.14>—Perform the test with 4.0 g of D- Sorbitol. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.006z). Heavy metals <1.07>—Proceed with 5.0 g of D-Sorbitol according to Method 1, and perform the test. Prepare the control solution with 2.5 mL of Standard Lead Solution (not more than 5 ppm). Nickel—Dissolve 0.5 g of D-Sorbitol in 5 mL of water, add 3 drops of dimethylglyoxime TS and 3 drops of ammonia TS, and allow to stand for 5 minutes: no red color develops. Arsenic <1.11>—Prepare the test solution with 1.5 g of D-Sorbitol according to Method 1, and perform the test (not more than 1.3 ppm). Glucose—Dissolve 20.0 g of D-Sorbitol in 25 mL of water, and boil gently with 40 mL of Fehling's TS for 3 minutes. After cooling, filter the supernatant liquid cau-tiously through a glass filter (G4), leaving the precipitate in the flask as much as possible, wash the precipitate with hot water until the last washings no longer show an alkali reac-tion, and filter the washings through the glass filter. Dissolve the precipitate in the flask in 20 mL of iron (III) sulfate TS, filter through the glass filter, and wash with water. Combine the filtrate and the washings, heat at 809C, and titrate <2.50> with 0.02 mol/L potassium permanganate VS: not more than 6.3 mL of volume for titration consumed or consump-tion is required. Sugars—Dissolve 20.0 g of D-Sorbitol in 25 mL of water, and heat with 8 mL of dilute hydrochloric acid under a reflux condenser in a water bath for 3 hours. After cool-ing, add 2 drops of methyl orange TS, followed by sodium hydroxide TS until an orange color develops, and add …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of D-Sorbitol, previ-ously dried, dissolve in water and add water to make exactly 100 mL. Pipet 10 mL of the solution into an iodine flask, add exactly 50 mL of potassium periodate TS, and heat for 15 minutes in a water bath. Cool, add 2.5 g of potassium iodide, immediately stopper tightly, and shake well. Allow to stand for 5 minutes in a dark place, and titrate <2.50> with 0.1 mol/L sodium thiosulfate VS (indicator: 3 mL of starch TS). Perform a blank determination in the same manner. Each mL of 0.1 mol/L sodium thiosulfate VS ＝ 1.822 mg of C6H14O6
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dactinomycin
type: ChemicalDrugMonograph
pref label:
  en: Dactinomycin
  ja: アクチノマイシン D
monograph id: JP18-dactinomycin
publisher: JP
status: Official
version: 18
molecular formula: C62H86N12O16
molecular weight: 1255.42
cas number: 50-76-0
appearance:
  en: Actinomycin D occurs as an orange-red to red crystalline powder. It is freely soluble in acetone, sparingly soluble in aceto-nitrile and in methanol, slightly soluble in ethanol (99.5), and very slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Actinomycin D in methanol (3 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Actinomycin D RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Dissolve 0.1 g each of Actinomycin D and Actinomy-cin D RS in 10 mL of acetone, and use these solutions as the sample solution and standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of 1-butanol, water and methanol (4:2:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the Rf value of the principal spot from the sample solution is the same as that from the standard solution. D Optical rotation <2.49> [a]20: －293 – －3299(after drying, 10 mg, methanol, 10 mL, 100 mm). Loss on drying <2.41> Not more than 5.0z (1 g, in vacu-um, 609C, 3 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Actinomycin D and Actinomycin D RS, previously dried, equivalent to about 60 mg (potency), dissolve each in the mobile phase to make ex-actly 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with exactly 25 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine the peak area of actino- mycin D, AT and AS, in each solution. Amount [ mg (potency)] of actinomycin D (C62H86N12O16) ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Actinomycin D RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 3.9 mm in inside diame-ter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of 0.02 mol/L acetic acid-sodi-um acetate TS and acetonitrile (25:23). Flow rate: Adjust so that the retention time of actinomy-cin D is about 23 minutes. System suitability— System performance: When the procedure is run with 25 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of actinomycin D are not less than 2000 and not more than 1.5, respectively. System repeatability: When the test is repeated 5 times with 25 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of actinomycin D is not more than 2.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

daiokanzoto-extract
type: ChemicalDrugMonograph
pref label:
  en: Daiokanzoto Extract
  ja: 大黄甘草湯エキス
monograph id: JP18-daiokanzoto-extract
publisher: JP
status: Official
version: 18
molecular formula: O20
molecular weight: 862.74
definition:
  en: Daiokanzoto Extract contains not less than 3.
appearance:
  en: Daiokanzoto Extract occurs as a brown pow-der. It has a characteristic odor and an astringent first then slightly sweet taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1.0 g of Daiokanzoto Extract add 10 mL of water, shake, then add 10 mL of diethyl ether, shake, centrifuge, and use the diethyl ether layer as the sample solu-tion. Separately, dissolve 1 mg of rhein for thin-layer chro-matography in 10 mL of acetone, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, methanol and water (20:3:2) to a distance of about 7 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 365 nm): one of the several spots obtained from the sample solution has the same color tone and Rf value with the orange fluo-rescent spot from the standard solution (Rhubarb). (2) To 0.5 g of Daiokanzoto Extract add 10 mL of water, shake, then add 10 mL of 1-butanol, shake, centrifuge, and use the 1-butanol layer as the sample solution. Separately, dissolve 1 mg of liquiritin for thin-layer chromatography in 1 mL of methanol, and use this solution as the standard solu-tion. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 1 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, methanol and water (20:3:2) to a acetate, shake for 10 minutes, centrifuge, and remove the ethyl acetate layer. To the aqueous layer add 10 mL of meth-anol, shake for 30 minutes, centrifuge, and take the superna-tant liquid. To the residue add 20 mL of diluted methanol (1 in 2), shake for 5 minutes, centrifuge, and take the superna-tant liquid. Combine these supernatant liquids, add diluted methanol (1 in 2) to make exactly 50 mL, and use this solu-tion as the sample solution. Separately, weigh accurately about 5 mg of Sennoside A RS (separately determine the wat…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Prepare the test solution with 1.0 g of Daiokanzoto Extract as directed under Extract (4), and perform the test (not more than 30 ppm). (2) Arsenic <1.11>—Prepare the test solution with 0.67 g of Daiokanzoto Extract according to Method 3, and perform the test (not more than 3 ppm). Loss on drying <2.41> Not more than 7.0z (1 g, 1059C, 5 hours). Total ash <5.01> Not more than 10.0z.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Sennoside A—Weigh accurately about 0.2 g of Daiokanzoto Extract, add 20 mL of ethyl acetate and 10 mL of sennoside A (C42 H38 O20 : 862.74), and not less than 7 of water, shake for 10 minutes, centrifuge, and remove the ethyl acetate layer. To the aqueous layer add 20 mL of ethyl mg and not more than 21 mg (for preparation prescribed 1 g of Glycyrrhiza) or not less than 14 mg and not more than 42 mg (for preparation prescribed 2 g of Glycyrrhiza) of glycyrrhizic acid (C42H62O16: 822.93), per extract prepared with the amount speci-fied in the Method of preparation. Method of preparation 1) 2) Rhubarb 4 g 4 g Glycyrrhiza 1 g 2 g Prepare a dry extract as directed under Extracts, according to the prescription 1) or 2), using the crude drugs shown above. Description Daiokanzoto Extract occurs as a brown pow-der. It has a characteristic odor and an astringent first then slightly sweet taste. Identification (1) To 1.0 g of Daiokanzoto Extract add 10 mL of water, shake, then add 10 mL of diethyl ether, shake, centrifuge, and use the diethyl ether layer as the sample solu-tion. Separately, dissolve 1 mg of rhein for thin-layer chro-matography in 10 mL of acetone, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, methanol and water (20:3:2) to a distance of about 7 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 365 nm): one of the several spots obtained from the sample solution has the same color tone and Rf value with the orange fluo-rescent spot from the standard solution (Rhubarb). (2) To 0.5 g of Daiokanzoto Extract add 10 mL of water, shake, then add 10 mL of 1-butanol, shake, centrifuge, and use the 1-butanol layer as the sample solution. Separately, dissolve 1 mg of liquiritin for thin…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

daisaikoto-extract
type: ChemicalDrugMonograph
pref label:
  en: Daisaikoto Extract
  ja: 大柴胡湯エキス
monograph id: JP18-daisaikoto-extract
publisher: JP
status: Official
version: 18
definition:
  en: Daisaikoto Extract contains not less than 1.
appearance:
  en: Daisaikoto Extract occurs as light yellow-brown to brown powder or black-brown viscous extract, having a slightly order, and a hot first, then a bitter taste.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Shake 1.0 g of the dry extract (or 3.0 g of the viscous extract) with 10 mL of water, add 10 mL of 1-butanol, shake, centrifuge, and use the 1-butanol layer as the sample solution. Separately, dissolve 1 mg of saikosaponin b2 for thin-layer chromatography in 1 mL of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chroma-tography <2.03>. Spot 10 mL of the sample solution and 2 mL of the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, ethanol (99.5) and water (8:2:1) to a distance of about 7 cm, and air-dry the plate. Spray evenly 4-dimethylaminobenzaldehyde TS for spraying on the plate, and heat the plate at 1059C for 5 minutes. Examine under ul-traviolet light (main wavelength: 365 nm): one of the several spots obtained from the sample solution has the same color tone and Rf value with the yellow fluorescent spot from the standard solution (Bupleurum Root). Shake 1.0 g of the dry extract (or 3.0 g of the viscous extract) with 10 mL of water, add 25 mL of diethyl ether, shake, and centrifuge. Separate the diethyl ether layer, evaporate the solvent under low pressure (in vacuo), add 2 mL of diethyl ether to the residue, and use this solution as the sample solution. Separately, dissolve 1 mg of wogonin for thin-layer chromatography in 1 mL of methanol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 20 mL of the sample solution and 5 mL of the standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, hexane and acetic acid (100) (10:10:1) to a distance of about 7 cm, and air-dry the plate. Spray evenly iron (III) chloride-methanol TS on the plate: one of the several spots obtained from the sample solution has the same color tone and Rf value with the yel…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Prepare the test solution with 1.0 g of the dry extract (or an amount of the viscous extract, equivalent to 1.0 g of dried substance) as directed under Extracts (4), and perform the test (not more than 30 ppm). (2) Arsenic <1.11>—Prepare the test solution with 0.67 g of the dry extract (or an amount of the viscous extract, equivalent to 0.67 g of dried substance) according to Method 3, and perform the test (not more than 3 ppm). Loss on drying <2.41> The dry extract: Not more than 11.0z (1 g, 1059C, 5 hours). The viscous extract: Not more than 66.7z (1 g, 1059C, 5 hours). Total ash <5.01> Not more than 9.0z, calculated on the dried basis.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Saikosaponin b2—Weigh accurately about 0.5 g of the dry extract (or an amount of the viscous extract, equivalent to about 0.5 g of the dried substance), add 20 mL of diethyl ether and 10 mL of water, and shake for 10 minutes. After centrifugation, remove the diethyl ether layer, add 20 mL of diethyl ether, proceed in the same man-ner as described above, and remove the diethyl ether layer. To the aqueous layer add 10 mL of methanol, shake for 30 minutes, centrifuge, and separate the supernatant liquid. To the residue add 20 mL of diluted methanol (1 in 2), shake for 5 minutes, centrifuge, separate the supernatant liquid, com-bine these supernatant liquids, add diluted methanol (1 in 2) to make exactly 50 mL, and use this solution as the sample solution. Separately, use saikosaponin b2 standard TS for assay as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of saikosaponin b2 in each solution. Amount (mg) of saikosaponin b2 ＝ CS × AT/AS × 50 CS: Concentration (mg/mL) of saikosaponin b2 in sai-kosaponin b2 standard TS for assay Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: A mixture of 0.05 mol/L sodium dihydro-gen phosphate TS and acetonitrile (5:3). Flow rate: 1.0 mL per minute (the retention time of saikosaponin b2 is about 12 minutes). System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of saikosaponin b2 are not less than 5000 and…
storage conditions:
  en: Containers—Tight containers.

danazol
type: ChemicalDrugMonograph
pref label:
  en: Danazol
  ja: ダナゾール
monograph id: JP18-danazol
publisher: JP
status: Official
version: 18
molecular formula: C22H27NO2
molecular weight: 337.46
definition:
  en: Danazol, when dried, contains not less than 98.
appearance:
  en: Danazol occurs as a white to pale yellow crys-talline powder. It is soluble in acetone, sparingly soluble in ethanol (99.5), and practically insoluble in water. Melting point: about 2259C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Danazol in ethanol (95) (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Danazol RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Danazol as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Danazol RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋8 – ＋119 (after drying, 0.25 g, ethanol (99.5), 50 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—To 2.0 g of Danazol add 80 mL of water, shake well, and boil for 5 minutes. After cool-ing, add water to make 100 mL, and filter through a glass filter (G4). Discard the first 30 mL of the filtrate, take 40 mL of the subsequent filtrate, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solu- Amount (mg) of danazol (C22H27NO2) ＝ MS × AT/AS MS: Amount (mg) of Danazol RS taken
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 25 mg each of Danazol and Danazol RS, previously dried, dissolve separately in ethanol (95) to make exactly 50 mL. Pipet 2 mL each of these solu-tions, add ethanol (95) to make exactly 50 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with the sample solution and standard solution as directed under Ultraviolet-visible Spec-trophotometry <2.24>, and determine the absorbances, AT and AS, at 285 nm. Danazol, when dried, contains not less than 98.5z and not more than 101.0z of danazol (C22H27NO2). Description Danazol occurs as a white to pale yellow crys-talline powder. It is soluble in acetone, sparingly soluble in ethanol (99.5), and practically insoluble in water. Melting point: about 2259C (with decomposition). Identification (1) Determine the absorption spectrum of a solution of Danazol in ethanol (95) (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Danazol RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Danazol as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Danazol RS: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋8 – ＋119 (after drying, 0.25 g, ethanol (99.5), 50 mL, 100 mm). Purity (1) Chloride <1.03>—To 2.0 g of Danazol add 80 mL of water, shake well, and boil for 5 minutes. After cool-ing, add water to make 100 mL, and filter through a glass filter (G4). Discard the first 30 mL of the filtrate, take 40 mL of the subsequent filtrate, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solu- Amount (mg) of danazol…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

daunorubicin-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Daunorubicin Hydrochloride
  ja: ダウノルビシン塩酸塩
monograph id: JP18-daunorubicin-hydrochloride
publisher: JP
status: Official
version: 18
cas number: 23541-50-6
definition:
  en: Daunorubicin Hydrochloride is the hydrochloride of an anthracycline substance having antitumor activity produced by the growth of Streptomyces peucetius or Streptomyces coeruleorubidus. It contains not less than 940 mg (potency) and not more than 1050 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Daunorubicin Hydrochloride occurs as a red powder. It is soluble in water and in methanol, and slightly soluble in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Daunorubicin Hydrochloride in methanol (1 in 100,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of a solution of Daunorubi-cin Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Daunorubicin Hydrochloride as directed in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum or the spectrum of Daunorubicin Hydrochloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Daunorubicin Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> (2) for chloride. D Optical rotation <2.49> [a]20: ＋250 – ＋2759(15 mg calcu-lated on the dried basis, methanol, 10 mL, 100 mm). pH <2.54> Dissolve 0.15 g of Daunorubicin Hydrochloride in 30 mL of water: the pH of the solution is between 4.5 and 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 20 mg of Daunorubicin Hydrochloride in 10 mL of water: the solu-tion is clear and red. Heavy metals <1.07>—Proceed with 1.0 g of Daunorubicin Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Weigh accurately about 50 mg of Daunorubicin Hydrochloride, dissolve in diluted aceto-nitrile (43 in 100) to make exactly 50 mL, and use this solu-tion as the sample solution. Separately, weigh accurately about 50 mg of Daunorubicin Hydrochloride RS, and dis-solve in diluted acetonitrile (43 in 100) to make exactly 50 mL. Pipet 1 mL of this solution, add diluted acetonitrile (43 in 100) to make exactly 200 mL, and use this solution as the standard solution (1). Separately, weigh accurately about 5 mg of Doxorubicin Hydrochloride RS, and dissolve in diluted acetonitrile (43 in 100) to make exactly 100 mL. Pipet 1 mL of this solution, add diluted acetonitrile (43 in 100) to make exactly 10 mL, and use this solution as the standard solution (2). Perform the test with exactly 5 mL each of the sample solution and standard solutions (1) and (2) as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area by the automatic integration method, and calculate the amounts of related substances by the following equations: each amount of each peak, having a relative retention time of about 0.3, about 0.6, about 0.7, about 0.8, about 1.7 and about 2.0 to daunorubicin, is not more than 1.3z, not more than 1.0z, not more than 0.3z, not more than 0.5z, not more than 0.4z and not more than 0.5z, respectively, and the amount of doxorubicin is not more than 0.4z. Furthermore, the total amount of the peaks, other than daunorubicin and the peaks mentioned above, is not more than 0.4z. For the area of the peak, having a relative retention time of about 0.3 to daunorubicin, multiply the correct…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Daunorubicin Hy-drochloride and Daunorubicin Hydrochloride RS, equiva-lent to about 20 mg (potency), dissolve each in a suitable amount of the mobile phase, add exactly 4 mL of the in-ternal standard solution and the mobile phase to make 20 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of daunorubicin to that of the internal standard. Amount [ mg (potency)] of daunorubicin hydrochloride (C27H29NO10.HCl) ＝ MS × QT/QS × 1000 MS: Amount [mg (potency)] of Daunorubicin Hydrochlo-ride RS taken sample solution Amount (z) of doxorubicin ＝ M S2/MT × AT/AS2 × 5 Internal standard solution—A solution of 2-naphthalenesul-fonic acid in the mobile phase (1 in 100). Operating conditions— MS2: Amount (mg) of Doxorubicin Hydrochloride RS taken MT: Amount (mg) of Daunorubicin Hydrochloride taken AS2: Peak area of doxorubicin obtained from the standard solution (2) AT: Peak area of doxorubicin obtained from the sample solution Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 30 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Adjust the pH of a mixture of water and ‌JP XVIII Official Monographs / Deferoxamine Mesilate 831 acetonitrile (31:19) to 2.2 with phosphoric acid. Flow rate: Adjust so that the retention time of daunorubi-cin is about 9 minutes. System suitability— System performance: When the procedure is run with 5 mL of the standard solution under the above operating condi-tions, the internal standard and daunorubicin are eluted in this order with the resolution between the…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

deferoxamine-mesilate
type: ChemicalDrugMonograph
pref label:
  en: Deferoxamine Mesilate
  ja: デフェロキサミンメシル酸塩
monograph id: JP18-deferoxamine-mesilate
publisher: JP
status: Official
version: 18
molecular formula: C25H48N6O8.CH4O3S
molecular weight: 656.79
definition:
  en: Deferoxamine Mesilate contains not less than 98.
appearance:
  en: Deferoxamine Mesilate occurs as a white to pale yellow-white crystalline powder. It is freely soluble in water, and practically insoluble in ethanol (99.5), in 2-propanol and in diethyl ether. Melting point: about 1479C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mL of a solution of Deferoxamine Mesilate (1 in 500) add 1 drop of iron (III) chloride TS: a deep red color develops. A 50 mg portion of Deferoxamine Mesilate responds to Qualitative Tests <1.09> (1) for mesilate. Determine the infrared absorption spectrum of Deferoxamine Mesilate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Deferoxamine Mesilate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. pH <2.54> Dissolve 1.0 g of Deferoxamine Mesilate in 10 mL of water: the pH of this solution is between 3.5 and 5.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Deferoxamine Mesilate in 10 mL of water: the solution is clear and colorless to pale yellow. Chloride <1.03>—Perform the test with 1.0 g of Deferoxamine Mesilate. Prepare the control solution with 0.90 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.032z). Sulfate <1.14>—Perform the test with 0.6 g of Deferoxamine Mesilate. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.040z). Heavy metals <1.07>—Proceed with 2.0 g of Deferox- amine Mesilate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Deferoxamine Mesilate according to Method 3, and per-form the test. Use a solution of magnesium nitrate hexahy-drate in ethanol (95) (1 in 10) (not more than 2 ppm). Related substances—Dissolve 50 mg of Deferoxa-mine Mesilata in 50 mL of the mobile phase, and use this so-lution as the sample solution. Pipet 3 mL of the sample solu-tion, add the mobile phase to make exactly 50 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions. Determine each peak area of both solutions by the automatic integration method: the total area of peaks other than deferoxamine obtained from the sample solution is not larger than the peak area of deferoxamine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 230 nm). Column: A stainless steel column 4 mm in inside diameter and 20 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (10 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 1.32 g of diammonium hydrogen phosphate, 0.37 g of disodium dihydro…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 60 mg of Deferoxamine Mesilate and Deferoxamine Mesilate RS (previously deter-mine the water <2.48> in the same manner as Deferoxamine ‌832 ‌Mesilate), dissolve each in 20 mL of water, add exactly 10 mL of 0.05 mol/L sulfuric acid TS, and add water to make exactly 50 mL. Pipet 5 mL each of these solutions, add exactly 5 mL of 0.05 mol/L sulfuric acid TS and exactly 0.2 mL of iron (III) chloride TS, then add water to make exactly 50 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with these solutions as directed under Ultraviolet-visible Spectro-photometry <2.24>, using a solution prepared by adding 0.05 mol/L sulfuric acid TS to 0.2 mL of iron (III) chloride TS to make exactly 50 mL as the blank, and determine the absor-bances, AT and AS, of each solution from the sample solu-tion and the standard solution at 430 nm. Amount (mg) of deferoxamine mesilate (C25H48N6O8.CH4O3S) ＝ MS × AT/AS MS: Amount (mg) of Deferoxamine Mesilate RS taken, calculated on the anhydrous basis
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dehydrated-alcohol
type: ChemicalDrugMonograph
pref label:
  en: Dehydrated Alcohol
  ja: 無水エタノール
monograph id: JP18-dehydrated-alcohol
publisher: JP
status: Official
version: 18
appearance:
  en: Anhydrous Ethanol is a clear, colorless liquid. It is miscible with water. It is flammable and burns with a light blue flame on igni-tion. It is volatile. Boiling point: 78 – 799C◆
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Determine the infrared absorption spectrum of Anhydrous Ethanol as directed in the liquid film method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Specific gravity <2.56> d 15: 0.79422 – 0.79679
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Anhydrouse Ethanol is clear and colorless. To 1.0 mL of Anhydrous Ethanol add water to make 20 mL, and allow to stand for 5 minutes: the resulting liquid is clear. Control solution: water ‌966 Acidity or alkalinity—To 20 mL of Anhydrous Ethanol add 20 mL of freshly boiled and cooled water and 0.1 mL of a solution obtained by addition of 7.0 mL of ethanol (95) and 2.0 mL of water to 1.0 mL of phenolphthal-ein TS: no color develops. Add 1.0 mL of 0.01 mol/L so-dium hydroxide VS to this solution: pink color develops. Volatile impurities—Pipet 500 mL of Anhydrous Ethanol, add 150 mL of 4-methylpentan-2-ol, and use this so-lution as the sample solution. Separately, to 100 mL of anhy-drous methanol add Anhydrous Ethanol to make exactly 50 mL. Pipet 5 mL of this solution, add Anhydrous Ethanol to make exactly 50 mL, and use this solution as the standard solution (1). Separately, to 50 mL each of anhydrous metha-nol and acetaldehyde add Anhydrous Ethanol to make ex-actly 50 mL. To 100 mL of this solution add Anhydrous Ethanol to make exactly 10 mL, and use this solution as the standard solution (2). Separately, to 150 mL of acetal add Anhydrous Ethanol to make exactly 50 mL. To 100 mL of this solution add Anhydrous Ethanol to make exactly 10 mL, and use this solution as the standard solution (3). Sepa-rately, to 100 mL of benzene add Anhydrous Ethanol to make exactly 100 mL. To 100 mL of this solution add Anhy-drous Ethanol to make exactly 50 mL, and use this solution as the standard solution (4). Perform the test with exactly 1 mL each of Anhydrous Ethanol, the sample solution and standard solutions (1), (2), (3) and (4) as directed under Gas Chromatography <2.02> according to the following condi-tions, and determine the peak areas of acetaldehyde, AE, benzene, BE and acetal, CE obtained with Anhydrous Ethanol, and the peak area of methanol with the standard solution (1), the peak area of acetaldehyde, AT with the standard solution (2), th…
storage conditions:
  en: ◆Containers—Tight containers.◆ Storage—Without exposure to light.
type: PharmacopoeiaMonograph

dehydrocholic-acid
type: ChemicalDrugMonograph
pref label:
  en: Dehydrocholic Acid
  ja: デヒドロコール酸
monograph id: JP18-dehydrocholic-acid
publisher: JP
status: Official
version: 18
molecular formula: C24H34O5
molecular weight: 402.52
definition:
  en: Dehydrocholic Acid, when dried, contains not less lution is clear and colorless.
appearance:
  en: Dehydrocholic Acid occurs as a white crystal-line powder. It is odorless, and has a bitter taste. It is sparingly soluble in acetone, slightly soluble in ethanol (95), and practically insoluble in water. It dissolves in sodium hydroxide TS.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 5 mg of Dehydrocholic Acid in 1 mL of sulfuric acid and 1 drop of formaldehyde solution, and allow to stand for 5 minutes. Add 5 mL of water to the solution: the solution shows a yellow color and a blue-green fluorescence. (2) To 0.02 g of Dehydrocholic Acid add 1 mL of ethanol (95), shake, add 5 drops of 1,3-dinitrobenzene TS and 0.5 mL of a solution of sodium hydroxide (1 in 8), and allow to stand: a purple to red-purple color develops, and gradually changes to brown. D Optical rotation <2.49> [a]25: ＋20 – ＋269(after drying, 0.2 g, acetone, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Odor—To 2.0 g of Dehydrocholic Acid add 100 mL of water, and boil for 2 minutes: the solution is Each mL of 0.1 mol/L sodium hydroxide VS ＝ 40.25 mg of C24H34O5
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Dehydrocholic Acid, previously dried, add 40 mL of neutralized ethanol and 20 mL of water, and dissolve by warming. Add 2 drops of phenolphthalein TS, titrate <2.50> with 0.1 mol/L sodium hydroxide VS, adding 100 mL of freshly boiled and cooled water as the end point is approached, and continue the titra- than 98.5z of dehydrocholic acid (C24 H34 O5). tion. Description Dehydrocholic Acid occurs as a white crystal-line powder. It is odorless, and has a bitter taste. It is sparingly soluble in acetone, slightly soluble in ethanol (95), and practically insoluble in water. It dissolves in sodium hydroxide TS. Identification (1) Dissolve 5 mg of Dehydrocholic Acid in 1 mL of sulfuric acid and 1 drop of formaldehyde solution, and allow to stand for 5 minutes. Add 5 mL of water to the solution: the solution shows a yellow color and a blue-green fluorescence. (2) To 0.02 g of Dehydrocholic Acid add 1 mL of ethanol (95), shake, add 5 drops of 1,3-dinitrobenzene TS and 0.5 mL of a solution of sodium hydroxide (1 in 8), and allow to stand: a purple to red-purple color develops, and gradually changes to brown. D Optical rotation <2.49> [a]25: ＋20 – ＋269(after drying, 0.2 g, acetone, 10 mL, 100 mm). Melting point <2.60> 233 – 2429C Purity (1) Odor—To 2.0 g of Dehydrocholic Acid add 100 mL of water, and boil for 2 minutes: the solution is Each mL of 0.1 mol/L sodium hydroxide VS ＝ 40.25 mg of C24H34O5
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

demethylchlortetracycline-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Demethylchlortetracycline Hydrochloride
  ja: デメチルクロルテトラサイクリン塩酸塩
monograph id: JP18-demethylchlortetracycline-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C21H21ClN2O8.HCl
molecular weight: 501.31
cas number: 64-73-3
definition:
  en: Demethylchlortetracycline Hydrochloride is the hy-drochloride of a tetracycline substance having antibac-terial activity produced by the growth of the mutant of Streptomyces aureofaciens. It contains not less than 900 mg (potency) and not more than 1010 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Demethylchlortetracycline Hydrochloride oc-curs as a yellow crystalline powder. It is soluble in water, and slightly soluble in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 40 mg of Demethylchlortetra-cycline Hydrochloride in 250 mL of water. To 10 mL of this solution add 85 mL of water and 5 mL of a solution of so-dium hydroxide (1 in 5). Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum or the spectrum of a solution of Demethyl-chlortetracycline Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Demethylchlortetracycline Hydrochloride as directed in the potassium chloride disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum or the spectrum of Demethylchlortetracycline Hydrochloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Demethylchlortetracycline Hydrochlo-ride (1 in 100) responds to Qualitative Tests <1.09> (2) for chloride. D Optical rotation <2.49> [a]20: －248 – －2639(0.25 g calcu-lated on the dried basis, 0.1 mol/L hydrochloric acid TS, 25 mL, 100 mm). (2) Related substances—Dissolve 25 mg of Demethyl-chlortetracycline Hydrochloride in 50 mL of 0.01 mol/L hydrochloric acid TS, and use this solution as the sample solution. Pipet 5 mL of the sample solution, add 0.01 mol/L hydrochloric acid TS to make exactly 100 mL, and use this solution as the standard solution. Perform the test with ex-actly 20 mL each of the sample solution and standard solu-tion as directed under Liquid Chromatography <2.01> ac-cording to the following conditions. Determine each peak area by the automatic integration method: the area of the peak other than demethylchlortetracycline obtained from the sample solution is not larger than 1.2 times the peak area of demethylchlortetracycline from the standard solution, and the total area of the peaks other than demethylchlortetra-cy…
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Demethylchlortetracycline Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Demethylchlortetracycline Hydrochloride RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.1 mm in inside diame-ter and 25 cm in length, packed with styrene-divinylbenzene ‌JP XVIII Official Monographs / Deslanoside 835 copolymer for liquid chromatography (10 mm in particle di-ameter). Column temperature: A constant temperature of about 609C. Mobile phase: Dissolve 3.5 g of dipotassium hydrogen phosphate, 1.5 g of tetrabutylammonium hydrogensulfate and 0.4 g of disodium dihydrogen ethylenediamine tetra-acetate dihydrate in 300 mL of water, and adjust the pH to 8.5 with sodium hydroxide TS. To this solution add 75.0 g of t-butanol and water to make 1000 mL. Flow rate: Adjust so that the retention time of demethyl-chlortetracycline is about 8 minutes. System suitability— System performance: Heat 10 mL of the standard solution on a water bath for 60 minutes. When the procedure is run with 20 mL of this solution so obtained under the above operating conditions, 4-epidemethylchlortetracycline and demethylchlortetracycline are eluted in this order with the resolution between these peaks being not less than 3. The relative retention time of 4-epidemethylchlortetracycline to demethylchlortetracycline is about 0.7. ‌System repeatability: When the test is repeated 6 times with 20 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of demethylchlortetracycline is not more than 1.0z.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately an amount of Demethylchlortetra-cycline Hydrochloride and Demethylchlortetracycline Hy-drochloride RS, equivalent to about 25 mg (potency), dis-solve each in 0.01 mol/L hydrochloric acid TS to make exactly 50 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of demethylchlortetracycline in each solution. Amount [ mg (potency)] of demethylchlortetracycline hydrochloride (C H ClN O .HCl) 21 21 2 8 pH <2.54> Dissolve 1.0 g of Demethylchlortetracycline Hy- drochloride in 100 mL of water: the pH of the solution is be-tween 2.0 and 3.0. Purity (1) Heavy metals <1.07>—Proceed with 1.0 g of Demethylchlortetracycline Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Demethylchlortetracycline Hydrochloride RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.1 mm in inside diame-ter and 25 cm in length, packed with styrene-divinylbenzene ‌JP XVIII Official Monographs / Deslanoside 835 copolymer for liquid chromatography (10 mm in particle di-ameter). Column temperature: A constant temperature of about 609C. Mobile phase: Dissolve 3.5 g of dipotassium hydrogen phosphate, 1.5 g of tetrabutylammonium hydrogensulfate and 0.4 g of disodium dihydrogen ethylenediamine tetra-acetate dihydrate in 300 mL of water, and adjust the pH to 8.5 with sodium hydroxide TS. To this solution add 75.0 g of t-butanol and water to make 1000 mL. Flow rate: Adjust so that the retention time of demethyl-chlortetracycline is about 8 minutes. System suitability— System performance: Heat 10 mL of the standard s…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

dental-iodine-glycerin
type: ChemicalDrugMonograph
pref label:
  en: Dental Iodine Glycerin
  ja: 歯科用ヨード・グリセリン
monograph id: JP18-dental-iodine-glycerin
publisher: JP
status: Official
version: 18
definition:
  en: Dental Iodine Glycerin contains not less than 9.
appearance:
  en: Dental Iodine Glycerin is a dark red-brown liq-uid, having the odor of iodine.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) The colored solution obtained in the Assay (1) acquires a red color. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhibits a maximum be-tween 510 nm and 514 nm (iodine). The colored solution obtained in the Assay (2) acquires a red color. Determine the absorption spectrum of this solution as directed under Ultraviolet-visible Spectro-photometry <2.24>: it exhibits a maximum between 510 nm and 514 nm (potassium iodide). Put 1 mL of Dental Iodine Glycerin in a glass-stoppered, test tube, add 10 mL of ethanol (95), and mix. Then add 2 mL of sodium hydroxide TS, add 1 mL of a so-lution of copper (II) chloride dihydrate in ethanol (95) (1 in 10), and shake: a blue color develops (glycerin). The colored solution obtained in the Assay (3) acquires a red-purple to purple color. Determine the absorp-tion spectrum of this solution as directed under Ultraviolet-visible Spectrophotometry <2.24>: it exhibits a maximum be-tween 618 nm and 622 nm (zinc sulfate hydrate).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Iodine—Pipet 5 mL of Dental Iodine Glycerin, ‌JP XVIII Official Monographs / Iodine, Salicylic Acid and Phenol Spirit 1173 and add diluted ethanol (3 in 10) to make exactly 50 mL. Pipet 5 mL of this solution, add water to make exactly 200 mL, and use this solution as the sample solution. On the other hand, weigh accurately about 0.5 g of iodine for assay and about 0.4 g of potassium iodide for assay, previously dried at 1059C for 4 hours, and dissolve in diluted ethanol (3 in 10) to make exactly 50 mL. Pipet 5 mL of this solution, add water to make exactly 200 mL, and use this solution as the standard solution. Pipet 10 mL each of the sample solu-tion and standard solution, to each add exactly 20 mL of a mixture of chloroform and hexane (2:1), shake immediately, and separate the chloroform-hexane layer [use the water layer in (2)]. Filter through a pledget of cotton. Determine the absorbances, AT and AS, of the filtrates obtained from the sample solution and standard solution, respectively, at 512 nm as directed under Ultraviolet-visible Spectropho-tometry <2.24>, using a mixture of chloroform and hexane (2:1) as the blank. Amount (mg) of iodine (I) ＝ MS × AT/AS MS: Amount (mg) of iodine for assay taken Potassium iodide—Separate the water layers of the sample solution and standard solution obtained in (1), pipet 7 mL each of the water layers, and to each add exactly 1 mL of diluted hydrochloric acid (1 in 2), 1 mL of sodium nitrite TS and 10 mL of a mixture of chloroform and hexane (2:1), and shake immediately. Separate the chloroform-hexane layer, and filter through a pledget of cotton. Determine the absorbances, AT and AS, of the filtrates obtained from the sample solution and standard solution, respectively, at 512 nm as directed under Ultraviolet-visible Spectrophotometry, using a mixture of chloroform and hexane (2:1) as the blank. Amount (mg) of potassium iodide (KI) ＝ MS × AT/AS MS: Amount (mg) of potassium iodide for assay taken Zinc sulfate hydrate—Pipe…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

dental-paraformaldehyde-paste
type: ChemicalDrugMonograph
pref label:
  en: Dental Paraformaldehyde Paste
  ja: 歯科用パラホルムパスタ
monograph id: JP18-dental-paraformaldehyde-paste
publisher: JP
status: Official
version: 18
appearance:
  en: Dental Paraformaldehyde Paste is yellowish white in color. It has a characteristic odor.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 0.15 g of Dental Paraformaldehyde Paste add 20 mL of diethyl ether and 20 mL of 0.5 mol/L sodium hydroxide TS, shake well, separate the water layer, and dilute with water to make 100 mL. To 1 mL of this solu-tion add 10 mL of acetylacetone TS, and heat on a water bath for 10 minutes: a yellow color is produced (paraformal-dehyde). To the diethyl ether layer obtained in (1) add 5 mL of dilute hydrochloric acid and 20 mL of water, shake well, and separate the water layer: the solution responds to Qualitative Tests <1.09> for primary aromatic amines (procaine hydro-chloride). To 0.15 g of Dental Paraformaldehyde Paste add 25 mL of diethyl ether and 25 mL of water, shake, separate the water layer, filter, and use the filtrate as the sample solution. Separately, dissolve 0.01 g of procaine hydrochloride in 5 mL of water, and use this solution as standard solution. Per-form the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Devel-op the plate with a mixture of ethyl acetate, ethanol (99.5) and ammonia solution (28) (50:5:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): spots obtained from the sample solution and standard solution show the same Rf value.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dental-phenol-with-camphor
type: ChemicalDrugMonograph
pref label:
  en: Dental Phenol with Camphor
  ja: 歯科用フェノール・カンフル
monograph id: JP18-dental-phenol-with-camphor
publisher: JP
status: Official
version: 18
appearance:
  en: Dental Phenol with Camphor is a colorless or light red liquid. It has a characteristic odor.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

deslanoside
type: ChemicalDrugMonograph
pref label:
  en: Deslanoside
  ja: デスラノシド
monograph id: JP18-deslanoside
publisher: JP
status: Official
version: 18
molecular formula: C47H74O19
molecular weight: 943.08
definition:
  en: Deslanoside, when dried, contains not less than 90.
appearance:
  en: Deslanoside occurs as colorless or white crys-tals or a white, crystalline powder. It is odorless. It is freely soluble in dehydrated pyridine, sparingly solu-ble in methanol, slightly soluble in ethanol (95), and practi- MS: Amount (mg) of Deslanoside RS taken
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Transfer 1 mg of Deslanoside to a small test tube about 10 mm in inside diameter, dissolve in 1 mL of a solution of iron (III) chloride hexahydrate in acetic acid (100) (1 in 1000), and underlay gently with 1 mL of sulfuric acid: at the zone of contact of two liquids a brown ring is produced, and the color of the upper layer near to the con-tact zone changes gradually to blue through purple, and the entire acetic acid layer shows a blue-green color through a deep blue color.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 20 mg of Deslanoside in 10 mL of ethanol (95) and 3 mL of water by warming, cool, and dilute to 100 mL with water: the solu-tion is clear and colorless. (2) Related substances—Dissolve 10 mg of Deslanoside in exactly 5 mL of methanol, and use this solution as the sample solution. Dissolve 1.0 mg of Deslanoside RS in exactly 5 mL of methanol, and use this solution as the stand-ard solution. Perform the test with these solutions as di-rected under Thin-layer Chromatography <2.03>. Spot 20 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, methanol and water (84:15:1) to a distance of about 13 cm, and air-dry the plate. Spray evenly dilute sulfuric acid on the plate, and heat the plate at 1109C for 10 minutes: the spots other than the principal spot obtained from the sample solution are not larger and not more intense than the spot from the standard solution. D Optical rotation <2.49> [a]20: ＋6.5 – ＋8.59(after drying, 0.5 g, dehydrated pyridine, 25 mL, 100 mm). Loss on drying <2.41> Not more than 8.0z (0.5 g, in vacu-um, phosphorus (V) oxide, 609C, 4 hours). Residue on ignition <2.44> Not more than 0.5z (0.1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Dissolve about 12 mg each of Deslanoside and Des-lanoside RS, previously dried and accurately weighed, in 20 mL each of methanol, add water to make exactly 100 mL, and use these solutions as the sample solution and the stand-ard solution, respectively. Pipet 5 mL each of these solu-tions, transfer to light-resistant, 25-mL volumetric flasks, shake well with 5 mL each of 2,4,6-trinitrophenol TS and 0.5 mL each of a solution of sodium hydroxide (1 in 10), add diluted methanol (1 in 4) to make 25 mL, and allow to stand at a temperature between 189C and 229C for 25 minutes. De-termine the absorbances, AT and AS, of the subsequent solu-tions of the sample solution and the standard solution, re-spectively, at 485 nm as directed under Ultraviolet-visible Spectrophotometry <2.24>, using a solution prepared with 5 mL of diluted methanol (1 in 5) in the same manner as the blank. hexopyranosyl-(1→4)-2,6-dideoxy-b-D-ribo-hexopyranosyloxy]-12b,14-dihydroxy-5b,14b-card-20(22)- Amount (mg) of deslanoside (C 47H 74O 19) ＝ MS × AT/AS enolide [17598-65-1] Deslanoside, when dried, contains not less than 90.0z and not more than 102.0z of deslanoside (C47H74O19). Description Deslanoside occurs as colorless or white crys-tals or a white, crystalline powder. It is odorless. It is freely soluble in dehydrated pyridine, sparingly solu-ble in methanol, slightly soluble in ethanol (95), and practi- MS: Amount (mg) of Deslanoside RS taken
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dexamethasone
type: ChemicalDrugMonograph
pref label:
  en: Dexamethasone
  ja: デキサメタゾン
monograph id: JP18-dexamethasone
publisher: JP
status: Official
version: 18
molecular formula: C22H29FO5
molecular weight: 392.46
cas number: 50-02-2
definition:
  en: Dexamethasone, when dried, contains not less than 97.
appearance:
  en: Dexamethasone occurs as white to pale yellow, crystals or crystalline powder. It is sparingly soluble in methanol, in ethanol (95) and in acetone, slightly soluble in acetonitrile, and practically in-soluble in water. Melting point: about 2459C (with decomposition). It shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Place a volume of Deslanoside Injec-tion, equivalent to 2 mg of Deslanoside, in a separator, add sodium chloride in the ratio of 0.2 g to each mL of this solu-tion, and extract with three 10-mL portions of chloroform. Combine the chloroform extracts, mix uniformly, pipet 15 mL of this solution, and evaporate the chloroform under reduced pressure. Proceed with the residue as directed in the Identification under Deslanoside. (2) Evaporate the remaining chloroform extract obtained in (1) under reduced pressure, dissolve the residue in 5 mL of methanol, and use this solution as the sample solution. Sepa-rately, dissolve 1 mg of Deslanoside RS in 5 mL of metha-nol, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 20 mL each of these solutions on a plate of silica gel for thin-layer chromatography. De-velop the plate with a mixture of dichloromethane, methanol and water (84:15:1) to a distance of about 13 cm, and air-dry the plate. Spray evenly dilute sulfuric acid upon the plate, and heat the plate at 1109C for 10 minutes: the spots from the sample solution and standard solution show a black color and have the same Rf value. Bacterial endotoxins <4.01> Less than 500 EU/mg. Extractable volume <6.05> It meets the requirement. Foreign insoluble matter <6.06> Perform the test according to Method 1: it meets the requirement. Insoluble particulate matter <6.07> It meets the require-ment. Sterility <4.06> Perform the test according to the Mem-brane filtration method: it meets the requirement.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Dexamethasone according to Method 2, and perform the test. Prepare the control solution with 3.0 mL of Standard MS: Amount (mg) of Deslanoside RS taken
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Measure exactly a volume of Deslanoside Injection, equivalent to about 3 mg of deslanoside (C47H74O19). Add 5 mL of methanol and water to make exactly 25 mL. Use this solution as the sample solution, and proceed as directed in the Assay under Deslanoside. Description Dexamethasone occurs as white to pale yellow, crystals or crystalline powder. It is sparingly soluble in methanol, in ethanol (95) and in acetone, slightly soluble in acetonitrile, and practically in-soluble in water. Melting point: about 2459C (with decomposition). It shows crystal polymorphism. Identification (1) Proceed with 10 mg of Dexamethasone as directed under Oxygen Flask Combustion Method <1.06>, using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as the absorbing liquid: the solution obtained responds to Qualitative Tests <1.09> for fluoride. Dissolve 1 mg of Dexamethasone in 10 mL of ethanol (95). Mix 2 mL of the solution with 10 mL of phenyl-hydrazinium chloride TS, heat in a water bath at 609C for 20 minutes, and cool the solution. Determine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, using as the blank the solution prepared with 2 mL of ethanol (95) in the same manner as the former solution, and compare the spectrum with the Ref-erence Spectrum or the spectrum of a solution of Dexa-methasone RS prepared in the same manner as the former solution: both spectra exhibit similar intensities of absorp-tion at the same wavelengths. Determine the infrared absorption spectrum of Dexa-methasone, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum or the spectrum of previously dried Dexamethasone RS: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, dissolve Dexamethasone and Dexamethasone RS in acetone, respectively, then evapo…
storage conditions:
  en: Containers—Hermetic containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

dextrin
type: ChemicalDrugMonograph
pref label:
  en: Dextrin
  ja: デキストリン
monograph id: JP18-dextrin
publisher: JP
status: Official
version: 18
appearance:
  en: Dextrin occurs as a white or light yellow, amorphous powder or granules. It has a slight, characteristic odor and a sweet taste. It does not irritate the tongue. Dextrin is freely soluble in boiling water, soluble in water, and practically insoluble in ethanol (95) and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 0.1 g of Dextrin add 100 mL of water, shake, and filter if necessary. To 5 mL of the filtrate add 1 drop of iodine TS: a light red-brown or light red-purple color develops.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Take 2.0 g of Dextrin in a Nessler tube, add 40 mL of water, dissolve by heating, cool, and add water to make 50 mL: the solution is colorless or light yellow. It is clear, and even if turbid, the turbidity is not more than that of the following control solu-tion. Control solution: To 1.0 mL of 0.005 mol/L sulfuric acid VS add 1 mL of dilute hydrochloric acid, 46 mL of water and 2 mL of barium chloride TS, allow to stand for 10 minutes, and shake before use. Acidity—To 1.0 g of Dextrin add 5 mL of water, dis-solve by heating, cool, and add 1 drop of phenolphthalein TS and 0.50 mL of 0.1 mol/L sodium hydroxide VS: a red color develops. Chloride <1.03>—To 2.0 g of Dextrin add 80 mL of water, dissolve by heating, cool, add water to make 100 mL, and filter. Take 40 mL of the filtrate, and add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.013z). Sulfate <1.14>—To 45 mL of the filtrate obtained in (3) add 1 mL of dilute hydrochloric acid and water to make 50 mL, and perform the test using this solution as the test so-lution. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.019z). Oxalate—To 1.0 g of Dextrin add 20 mL of water, dissolve by heating, cool, add 1 mL of acetic acid (31), and filter. To 5 mL of the filtrate add 5 drops of calcium chloride TS: no turbidity is produced immediately. Calcium—To a 5-mL portion of the filtrate obtained in (5) add 5 drops of ammonium oxalate TS: no turbidity is immediately produced. Heavy metals <1.07>—Proceed with 0.5 g of Dextrin according to Method 2, and perform the test. Prepare the control solution with 2.5 mL of Standard Lead Solution (not more than 50 ppm). Loss on drying <2.41> Not more than 10z (0.5 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.5z (0.5 g).
storage conditions:
  en: Containers—Well-closed contain-ers.

dextromethorphan-hydrobromide-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Dextromethorphan Hydrobromide Hydrate
  ja: デキストロメトルファン臭化水素酸塩水和物
monograph id: JP18-dextromethorphan-hydrobromide-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C18H25NO.HBr.H2O
molecular weight: 370.32
cas number: 6700-34-1
appearance:
  en: Dextromethorphan Hydrobromide Hydrate occurs as white, crystals or crystalline powder. It is very soluble in methanol, freely soluble in ethanol (95) and in acetic acid (100), and sparingly soluble in water. Melting point: about 1269C (Insert the capillary tube into the bath preheated to 1169C, and continue the heating so that the temperature rises at a rate of about 39C per minute.)
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Dextromethorphan Hydrobromide Hydrate (1 in 10,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Dex-tromethorphan Hydrobromide Hydrate as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wave numbers. To 50 mL of a solution of Dextromethorphan Hydrobromide Hydrate (1 in 100) add 2 drops of phenol-phalein TS and sodium hydroxide TS until a red color de-velops. Add 50 mL of chloroform, shake, and add 5 mL of dilute nitric acid to 40 mL of the water layer. This solution responds to Qualitative Tests <1.09> for bromide. D Optical rotation <2.49> [a]20: ＋26 – ＋309(0.34 g calcu-lated on the anhydrous basis, water, 20 mL, 100 mm). pH <2.54> Dissolve 1.0 g of Dextromethorphan Hydro-bromide Hydrate in 100 mL of water: the pH of this solution is between 5.2 and 6.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.20 g of Dextromethorphan Hydrobromide Hydrate in 20 mL of water: the solution is clear and colorless. N,N-dimethylaniline—To 0.50 g of Dextromethor-phan Hydrobromide Hydrate add 20 mL of water, and dis-solve by heating on a water bath. After cooling, add 2 mL of dilute acetic acid, 1 mL of sodium nitrite TS and water to make 25 mL: the solution has no more color than the follow-ing control solution. Control solution: Dissolve 0.10 g of N,N-dimethylaniline in 400 mL of water by warming on a water bath, cool, and add water to make 500 mL. Pipet 5 mL of this solution, and add water to make 200 mL. To 1.0 mL of this solution add 2 mL of dilute acetic acid, 1 mL of sodium nitrite TS and water to make 25 mL. Heavy metals <1.07>—Proceed with 1.0 g of Dex- tromethorphan Hydrobromide Hydrate according to Method 4, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Phenolic compounds—Dissolve 5 mg of Dextro-methorphan Hydrobromide Hydrate in 1 drop of dilute hy-drochloric acid and 1 mL of water, add 2 drops of iron (III) chloride TS and 2 drops of potassium hexacyanoferrate (III) TS, shake, and allow to stand for 15 minutes: no blue-green color develops. Related substances—Dissolve 0.25 g of Dextro-methorphan Hydrobromide Hydrate in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chro-matography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of tolu- ene, ethyl acetate, methanol, dichloromethane and 13.5 mol/L ammonia TS (55:20:13:10:2) to a distance of about 15 cm, and air-dry the plate. Spray evenly bismuth potassium iodide TS on the plate, and then spray evenl…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Dextromethorphan Hydrobromide Hydrate, dissolve in 10 mL of acetic acid (100) and add 40 mL of acetic anhydride. Titrate <2.50> with mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination, and make any necessary correc-tion. Each mL of 0.1 mol/L perchloric acid VS ＝ 35.23 mg of C18H25NO.HBr
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

diastase
type: ChemicalDrugMonograph
pref label:
  en: Diastase
  ja: ジアスターゼ
monograph id: JP18-diastase
publisher: JP
status: Official
version: 18
definition:
  en: Diastase is an enzyme drug mainly prepared from malt. It has amylolytic activity. It contains not less than 440 starch saccharifying activity units per g.
appearance:
  en: Diastase occurs as a light yellow to light brown powder. It is hygroscopic.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Rancidity—Diastase has no unpleasant or rancid odor, and has no unpleasant or rancid taste. Loss on drying <2.41> Not more than 4.0z (1 g, 1059C, 5 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (i) Substrate solution—Use potato starch TS for amylolytic activity test. Sample solution—Weigh accurately about 0.1 g of Diastase, and dissolve in water to make exactly 100 mL. Procedure—Proceed as directed in 1.1. Measure-ment of starch saccharifying activity of 1. Assay for starch digestive activity under Digestion Test <4.03>.
storage conditions:
  en: Containers—Tight containers. Storage—Not exceeding 309C.

diazepam
type: ChemicalDrugMonograph
pref label:
  en: Diazepam
  ja: ジアゼパム
monograph id: JP18-diazepam
publisher: JP
status: Official
version: 18
molecular formula: C16H13ClN2O
molecular weight: 284.74
cas number: 439-14-5
definition:
  en: Diazepam, when dried, contains not less than 98.
appearance:
  en: Diazepam occurs as a white to light yellow crystalline powder. It is odorless, and has a slightly bitter taste. It is freely soluble in acetone, soluble in acetic anhydride and in ethanol (95), sparingly soluble in diethyl ether, slightly soluble in ethanol (99.5), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 10 mg of Diazepam in 3 mL of sulfuric acid, and observe under ultraviolet light (main wave-length: 365 nm): the solution shows a yellow-green fluores-cence. Dissolve 2 mg of Diazepam in 200 mL of a solution of sulfuric acid in ethanol (99.5) (3 in 1000). Determine the absorption spectrum of the solution as directed under Ultra-violet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dia-zepam, previously dried, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. Perform the test with Diazepam as directed under Flame Coloration Test <1.04> (2): a blue to blue-green color appears.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity of solution—Dissolve 0.10 g of Diaze-pam in 20 mL of ethanol (95): the solution is clear. Chloride <1.03>—To 1.0 g of Diazepam add 50 mL of water, allow to stand for 1 hour, with occasional shaking, and filter. To 25 mL of the filtrate add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.20 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.014z). Heavy metals <1.07>—Proceed with 1.0 g of Diaze- pam according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 1.0 g of Diazepam in 10 mL of acetone, and use this solution as the sample solu-tion. Pipept 1 mL of the sample solution, and add acetone to make exactly 100 mL. Pipet 1 mL of this solution, add ace-tone to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate and hexane (1:1) to a distance of about 12 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 2 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Diazepam, previ-ously dried, dissolve in 60 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. ‌844 Each mL of 0.1 mol/L perchloric acid VS ＝ 28.47 mg of C16H13ClN2O
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

dibekacin-sulfate
type: ChemicalDrugMonograph
pref label:
  en: Dibekacin Sulfate
  ja: ジベカシン硫酸塩
monograph id: JP18-dibekacin-sulfate
publisher: JP
status: Official
version: 18
cas number: 58580-55-5
definition:
  en: Dibekacin Sulfate is the sulfate of a derivative of bekanamycin. It contains not less than 640 mg (potency) and not more than 740 mg (potency) per mg, calculated on the dried basis.
appearance:
  en: Dibekacin Sulfate occurs as a white to yellow-white powder. It is very soluble in water, and practically insoluble in ethanol (99.5).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 20 mg each of Dibekacin Sul-fate and Dibekacin Sulfate RS in 1 mL of water, and use these solutions as the sample solution and standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ammonia solution (28) and methanol (1:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly 0.2z ninhydrin-water saturated 1-butanol TS, and heat at 1009C for 10 minutes: the principal spots obtained from the sample solution and the spot from the standard solution show a purple-brown color and the same Rf value. (2) To 5 mL of a solution of Dibekacin Sulfate (1 in 50) add 1 drop of barium chloride TS: a white precipitate is pro-duced. D Optical rotation <2.49> [a]20: ＋96 – ＋1069(0.25 g calcu-lated on the dried basis, water, 25 mL, 100 mm). pH <2.54> The pH of a solution obtained by dissolving 1.0 g of Dibekacin Sulfate in 20 mL of water is between 6.0 and 8.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 3.0 g of Dibekacin Sulfate in 10 mL of water: the solution is clear. Determine the absorbance of this solution at 400 nm as di-rected under Ultraviolet-visible Spectrophotometry <2.24>: not more than 0.15. Heavy metals <1.07>—Proceed with 1.0 g of Dibeka- cin Sulfate according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Perform the test according to the Cylinder-plate method as directed under Microbial Assay for Antibiotics <4.02> according to the following conditions. Test organism—Bacillus subtilis ATCC 6633 Culture medium—Use the medium i in 1) under (1) Agar media for seed and base layer having pH 6.5 to 6.6 after sterilization. Standard solutions—Weigh accurately an amount of Dibekacin Sulfate RS, previously dried, equivalent to about 20 mg (potency), dissolve in diluted phosphate buffer solu-tion (pH 6.0) (1 in 2) to make exactly 50 mL, and use this so-lution as the standard stock solution. Keep the standard stock solution at 5 to 159C and use within 30 days. Take exactly a suitable amount of the standard stock solution be-fore use, add 0.1 mol/L phosphate buffer solution (pH 8.0) to make solutions so that each mL contains 20 mg (potency) and 5 mg (potency), and use these solutions as the high con-centration standard solution and the low concentration standard solution, respectively. Sample solutions—Weigh accurately an amount of Dibekacin Sulfate, equivalent to about 20 mg (potency), and dissolve in water to make exactly 50 mL. Take exactly a suitable amount of this solution, add 0.1 mol/L phosphate buffer solution (pH 8.0) to make solutions so that each mL contains 20 mg (potency) and 5 mg (potency), and use these pressed as mass (potency) of dibekacin (C 451.52). 18H37N5O8: solutions as the high concentration sample solution and the low concentration sample solution, respectively. Description Dibekacin Sulfate occurs as a white to yellow-white powder. It is very soluble in water, and practically insoluble in ethanol (99.5). Identification (1) Dissolve 20 mg each of Dibekacin Sul-fate and Dibekacin Sulfate RS in 1 mL of water, and use these solutions as the sample solution and standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for th…
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

diethylcarbamazine-citrate
type: ChemicalDrugMonograph
pref label:
  en: Diethylcarbamazine Citrate
  ja: ジエチルカルバマジンクエン酸塩
monograph id: JP18-diethylcarbamazine-citrate
publisher: JP
status: Official
version: 18
molecular formula: C10H21N3O.C6H8O7
molecular weight: 391.42
cas number: 1642-54-2
definition:
  en: Diethylcarbamazine Citrate, when dried, contains not less than 98.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

difenidol-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Difenidol Hydrochloride
  ja: ジフェニドール塩酸塩
monograph id: JP18-difenidol-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: H27NO.HCl
molecular weight: 345.91
cas number: 3254-89-5
definition:
  en: Difenidol Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Difenidol Hydrochloride occurs as white, crys-tals or crystalline powder. It is odorless. It is freely soluble in methanol, soluble in ethanol (95), sparingly soluble in water and in acetic acid (100), and prac-tically insoluble in diethyl ether. Melting point: about 2179C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.01 g of Difenidol Hydro-chloride in 1 mL of sulfuric acid: an orange-red color de-velops. To this solution add carefully 3 drops of water: the solution becomes yellowish brown, and colorless on the ad-dition of 10 mL of water. To 5 mL of a solution of Difenidol Hydrochloride (1 in 100) add 2 mL of Reinecke salt TS: a light red precipitate is formed. To 10 mL of a solution of Difenidol Hydrochloride (1 in 100) add 2 mL of sodium hydroxide TS, and extract with two 15-mL portions of chloroform. Combine the ex-tracts, wash with three 10-mL portions of water, evaporate the chloroform on a water bath, and dry the residue in a desiccator (in vacuum, silica gel, 559C) for 5 hours: the residue melts <2.60> between 1039C and 1069C. A solution of Difenidol Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Difenidol Hydrochloride in 100 mL of freshly boiled and cooled water: the pH of this solu-tion is between 4.7 and 6.5. JP XVIII Official Monographs / Diflorasone Diacetate 851 ‌Purity (1) Clarity and color of solution—Dissolve 1.0 g of Difenidol Hydrochloride in 10 mL of methanol: the solu-tion is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Difenidol Hydrochloride according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 2.0 g of Difenidol Hydrochloride according to Method 3, and per-form the test (not more than 1 ppm). Related substances—Dissolve 0.10 g of Difenidol Hydrochloride in methanol to make exactly 10 mL, and use this solution as the sample solution. Separately, dissolve 10 mg of 1,1-diphenyl-4-piperidino-1-butene hydrochloride for thin-layer chromatography in methanol to make exactly 20 mL, pipet 1 mL of this solution, add methanol to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.35 g of Difenidol Hydro-chloride, previously dried, dissolve in 30 mL of acetic acid (100) by warming if necessary, cool, add 30 mL of acetic an-hydride, and titrate <2.50> with 0.05 mol/L perchloric acid VS (potentiometric titration). Perform a blank determina-tion in the same manner, and make any necessary correction. Each mL of 0.05 mol/L perchloric acid VS ＝ 17.30 mg of C21H27NO.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

diflorasone-diacetate
type: ChemicalDrugMonograph
pref label:
  en: Diflorasone Diacetate
  ja: ジフロラゾン酢酸エステル
monograph id: JP18-diflorasone-diacetate
publisher: JP
status: Official
version: 18
molecular formula: C26H32F2O7
molecular weight: 494.52
cas number: 33564-31-7
definition:
  en: Diflorasone Diacetate, when dried, contains not less than 97.
appearance:
  en: Diflorasone Diacetate occurs as a white to pale yellow, crystals or crystalline powder. It is soluble in acetonitrile, slightly soluble in ethanol (99.5), and practically insoluble in water. Melting point: about 2229C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec-trum of Diflorasone Diacetate, previously dried, as directed in the potassium bromide disk method under Infrared Spec-trophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of previously dried Diflorasone Diacetate RS: both spectra exhibit similar inten-sities of absorption at the same wave numbers. (2) Prepare the test solution with 10 mg of Diflorasone Diacetate as directed under Oxygen Flask Combustion Method <1.06>, using 20 mL of diluted 0.01 mol/L sodium hydroxide VS (1 in 40) as the absorbing liquid: the test solu-tion responds to Qualitative Tests <1.09> for fluoride. D Optical rotation <2.49> [a]20: ＋ 88 – ＋ 939(after drying, 0.1 g, acetonitrile, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Diflorasone Diacetate according to Method 2, and perform the test. Prepare the control solution with 1.0 mL of Stand-ard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 20 mg of Diflorasone Diacetate in 20 mL of acetonitrile, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add acetonitrile to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method: the areas of the peaks, having a relative retention time of about 0.5, about 0.7, about 0.9 and about 1.1 to diflorasone diacetate, obtained from the sample solution are respectively not larger than 1/4 times, 1/4 times, 1/2 times and 3/4 times the peak area of diflorasone dia-cetate from the standard solution, and the total area of the peaks other than diflorasone diacetate and the peaks men-tioned above from the sample solutions is not larger than 1/5 times the peak area of diflorasone diacetate from the stand-ard solution. Furthermore, the total area of the peaks other than diflorasone diacetate from the sample solution is not larger than 1.5 times the peak area of diflorasone diacetate from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 1.4 times as long as the retention time of diflorasone diacetate, beginning after the solvent peak. System suitability— System performance: Proceed as directed in the system suitability in the Assay. Test for required detectability: Pipet 2 mL of the standard solution, and add acetonitrile to make exactly 20 mL. Con-firm that the peak area of diflorasone diacetate obtained with 10 mL of …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 20 mg each of Diflorasone Diacetate and Diflorasone Diacetate RS, both previously dried, dissolve in exactly 4 mL each of the internal standard solution, add acetonitrile to make them 20 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following condi-tions, and calculate the ratios, QT and QS, of the peak area of diflorasone diacetate to that of the internal standard. Amount (mg) of diflorasone diacetate (C26H23F2O7) ＝ MS × QT/QS MS: Amount (mg) of Diflorasone Diacetate RS taken Internal standard solution—A solution of methyl parahy-droxybenzoate in acetonitrile (1 in 1000). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 6 mm in inside diameter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Dissolve 6.8 g of potassium dihydrogen phosphate in 1000 mL of water, and adjust to pH 4.0 with diluted phosphoric acid (1 in 200). To 550 mL of this solu-tion add 400 mL of acetonitrile and 100 mL of tetrahydrofu-ran. Flow rate: Adjust so that the retention time of diflorasone diacetate is about 15 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the internal standard and diflorasone diacetate are eluted in this order with the resolution between these peaks being not less than 9. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratio of the peak area of diflorasone diacetate to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

diflucortolone-valerate
type: ChemicalDrugMonograph
pref label:
  en: Diflucortolone Valerate
  ja: ジフルコルトロン吉草酸エステル
monograph id: JP18-diflucortolone-valerate
publisher: JP
status: Official
version: 18
molecular formula: C27H36F2O5
molecular weight: 478.57
cas number: 59198-70-8
definition:
  en: Diflucortolone Valerate contains not less than 98.
appearance:
  en: Diflucortolone Valerate occurs as white, crys-tals or crystalline powder. It is sparingly soluble in methanol and in ethanol (99.5), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Prepare the test solution by proceeding with 10 mg of Diflucortolone Valerate according to Oxygen Flask Combustion Method <1.06>, using a mixture of 0.5 mL of 0.01 mol/L sodium hydroxide TS and 20 mL of water as the absorbing liquid: the test solution responds to Qualita-tive Tests <1.09> for fluoride. Determine the absorption spectrum of a solution of Diflucortolone Valerate in methanol (3 in 200,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Diflucortolone Valerate RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Diflucortolone Valerate as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Diflucortolone Valerate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋110 – ＋1159(0.1 g calcu-lated on the dried basis, ethanol (99.5), 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Diflucortolone Valerate in a platinum crucible according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Carbonize and incinerate as directed under Residue on Ignition <2.44>. (2) Related substances—Use the sample solution ob-tained in the Assay as the sample solution. Perform the test with 10 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the following condi-tions. Determine each peak area of sample solution by the automatic integration method, and calculate the amounts of these peaks by the area percentage method: the amount of each peak of flucortolone valerate, 12a diflucortolone valer-ate and D4 diflucortolone valerate, having the relative reten-tion times of about 0.97, 1.03 and 1.05 to diflucortolone valerate, respectively, is not more than 0.6z, respectively; the amount of the peak of clocortolone valerate, having the relative retention time of about 1.09, is not more than 0.3z; and the amount of each peak other than those mentioned above is not more than 0.1z. Furthermore, the total amount of the peaks other than diflucortolone valerate is not more than 2.0z. Operating conditions— Detector, column, column temperature, mobile phase and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 1.4 times as long as the retention time of diflucortolone valerate, beginning after the solvent peak. System suitability— System performance and system repeatability: Proceed as directed in the system suitability in the Assay. Test for required detectability: To 0.1 mL of the sample ‌JP XVIII Official Monographs / Digoxin 853 solution, add a mixture of water and acetonitrile (1:1) to make 10 mL, and use this solution as the solution for system suitability test. Pipet 1 mL of the solution for system suita-bility test, and add a mixture of water and acetonitrile (1:…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 5 mg each of Diflucortolone Valerate and Diflucortolone Valerate RS (separately, deter-mine the loss on drying <2.41> under the same conditions as Diflucortolone Valerate), dissolve each in a mixture of water and acetonitrile (1:1) to make exactly 10 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 10 mL each of the Digoxin
type: PharmacopoeiaMonograph

digenea
type: ChemicalDrugMonograph
pref label:
  en: Digenea
  ja: マクリ
monograph id: JP18-digenea
publisher: JP
status: Official
version: 18
appearance:
  en: Rounded, string-like algae, 2 – 3 mm in diame-ter; externally, dark red-purple to dark grayish red or grayish brown; a few branched rods irregularly forked, covered with short hairy twigs; calcified weeds and other small algae often attached. Odor, seaweed-like; taste, disagreeable and slightly salty.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: To 2 g of pulverized Digenea add 10 mL of dilute ethanol, shake for 15 minutes, filter, and use the fil-trate as the sample solution. Separately, dissolve 5 mg of kainic acid in 10 mL of dilute ethanol, and use this solution as the standard solution. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. De-velop the plate with a mixture of ethyl formate, water and formic acid (5:1:1) to a distance of about 7 cm, and air-dry the plate. Spray evenly ninhydrin-ethanol TS for spraying on the plate, and heat the plate at 1059C for 5 minutes: one of the several spots obtained from the sample solution has the same color tone and Rf value with the spot from the stand-ard solution.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Foreign matter <5.01>—The amount of other algae in Digenea does not exceed 20.0z. Loss on drying <5.01> Not more than 22.0z. Amount (mg) of paeoniflorin (C23H28O11) ＝ MS × AT/AS × 5/8 MS: Amount (mg) of Paeoniflorin RS taken, calculated on the anhydrous basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 232 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 209C. Mobile phase: A mixture of water, acetonitrile and phos- Acid-insoluble ash <5.01> Not more than 8.0z.
storage conditions:
  en: Containers—Well-closed contain-ers.

digoxin
type: ChemicalDrugMonograph
pref label:
  en: Digoxin
  ja: ジゴキシン
monograph id: JP18-digoxin
publisher: JP
status: Official
version: 18
definition:
  en: Digoxin, when dried, contains not less than 96.
appearance:
  en: Digoxin occurs as colorless or white crystals or a white crystalline powder. It is freely soluble in pyridine, slightly soluble in ethanol (95), very slightly soluble in acetic acid (100), and practically insoluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Transfer 1 mg of Digoxin to a small test tube about 10 mm in inside diameter, dissolve in 1 mL of a solution of iron (III) chloride hexahydrate in acetic acid (100) (1 in 10,000), and underlay gently with 1 mL of sulfuric acid: at the zone of contact of the two liquids a brown ring free from a reddish color is produced, and the color of the upper layer near the contact zone changes to green through purple. Finally the entire acetic acid layer shows a green color through a deep blue color. (2) Determine the infrared absorption spectrum of Digoxin, previously dried, as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋10.0 – ＋13.09(after dry-ing, 0.20 g, dehydratead pyridine, 10 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.10 g of Digoxin in 15 mL of diluted ethanol (95) (4 in 5) by warm-ing at 709C: the solution is clear and colorless. (2) Related substances—Dissolve 25.0 mg of Digoxin in 50 mL of warm ethanol (95), cool, and add ethanol (95) to make exactly 100 mL. Pipet 10 mL of this solution, add 10 mL of water and dilute ethanol to make exactly 50 mL, and use this solution as the sample solution. Separately, dissolve exactly 5.0 mg of Gitoxin for Purity RS, previously dried under reduced pressure at 1059C for 1 hour, in a mixture of acetonitrile and water (7:3) to make exactly 200 mL. Pipet 2 mL of this solution, add dilute ethanol to make exactly 50 mL, and use this solution as the standard solution. Perform ‌the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of gitoxin: AT is not larger than AS, and the total area of the peaks other than digoxin and gitoxin from the sample solution, obtained by the area per-centage method, is not more than 3z. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 4 times as long as the retention time of digoxin, beginning after the solvent peak. System suitability— Test for required detectability: Dissolve 25 mg of Digoxin in 50 mL of warm ethanol (95), cool, and add ethanol (95) to make 100 mL. To 10 mL of this solution add 10 mL of water and dilute ethanol to make 50 mL, and use this solution as the solution for system suitability test. Pipet 2 mL of the so-lution for system suitability test, and add dilute ethanol to make exactly 100 mL. Pipet 5 mL of this solution, and add dilute ethanol to make exactly 100 mL. Confirm that the peak area of digoxin obtained with 10 mL of this solution is equivalent to 0.07 to 0.13z of …
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 25 mg each of Digoxin and Digoxin RS, previously dried, dissolve in 50 mL of warm ethanol (95), cool, and add ethanol (95) to make exactly 100 mL. Pipet 10 mL of these solutions, add exactly 5 mL of the internal standard solution, 10 mL of water and dilute ethanol to make 50 mL, and use these solutions as the sample solution and standard solution. Perform the test with 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of digoxin to that of the internal stand-ard. 309C. Mobile phase: A mixture of water and acetonitrile (7:3). Flow rate: Adjust so that the retention time of digoxin is about 10 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, digoxin and the internal standard are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the ratio of the peak area of digoxin to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dihydrocodeine-phosphate
type: ChemicalDrugMonograph
pref label:
  en: Dihydrocodeine Phosphate
  ja: ジヒドロコデインリン酸塩
monograph id: JP18-dihydrocodeine-phosphate
publisher: JP
status: Official
version: 18
molecular formula: C18H23NO3.H3PO4
molecular weight: 399.38
cas number: 24204-13-5
definition:
  en: Dihydrocodeine Phosphate contains not less than 98.
appearance:
  en: Dihydrocodeine Phosphate occurs as a white to yellowish white crystalline powder. It is freely soluble in water and in acetic acid (100), slightly soluble in ethanol (95), and practically insoluble in diethyl ether. The pH of a solution of 1.0 g of Dihydrocodeine Phos-phate in 10 mL of water is between 3.0 and 5.0. It is affected by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Dihydrocodeine Phosphate (1 in 10,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared spectrum of Dihydrocodeine Phosphate, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Dihydrocodeine Phosphate (1 in 20) responds to Qualitative Tests <1.09> (1) for phosphate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Perform the test with 0.5 g of Dihydrocodeine Phosphate. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.021z). Sulfate <1.14>—Perform the test with 0.20 g of Dihy- drocodeine Phosphate. Prepare the control solution with 1.0 mL of 0.005 mol/L sulfuric acid VS (not more than 0.240z). Related substances—Dissolve 0.20 g of Dihydro-codeine Phosphate in 10 mL of diluted ethanol (1 in 2), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add diluted ethanol (1 in 2) to make exactly 50 mL, and use this solution as the standard solution. Per-form the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-chromatography. Develop the plate with a mixture of ethanol (99.5), toluene, acetone and ammonia solution (28) (14:14:7:1) to a distance of about 15 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the princi-pal spot obtained from the sample solution are not more in-tense than the spot from the standard solution. Loss on drying <2.41> Not more than 1.0z (0.5 g, 1059C, 4 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Dihydrocodeine Phosphate, dissolve in 70 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS until the color of the solution changes from purple through blue to greenish blue (indicator: 3 drops of crystal violet TS). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 39.94 mg of C18H23NO3.H3PO4
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

dihydroergotamine-mesilate
type: ChemicalDrugMonograph
pref label:
  en: Dihydroergotamine Mesilate
  ja: ジヒドロエルゴタミンメシル酸塩
monograph id: JP18-dihydroergotamine-mesilate
publisher: JP
status: Official
version: 18
molecular formula: C33H37N5O5.CH4O3S
molecular weight: 679.78
definition:
  en: Dihydroergotamine Mesilate contains not less than 97.
appearance:
  en: Dihydroergotamine Mesilate occurs as a white to yellowish white or grayish white to reddish white powder. It is freely soluble in acetic acid (100), sparingly soluble in methanol and in chloroform, slightly soluble in water and in ethanol (95), and practically insoluble in acetic anhydride and in diethyl ether. It is gradually colored by light. Melting point: about 2149C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 1 mg of Dihydroergotamine Mesilate in 5 mL of a solution of L-tartaric acid (1 in 100). To 1 mL of this solution add 2 mL of 4-dimethylaminoben-zaldehyde-ferric chloride TS, and shake: a blue color de-velops. To 0.1 g of Dihydroergotamine Mesilate add 0.4 g of sodium hydroxide, stir well, and incinerate by gradual igni-tion. After cooling, add 10 mL of water to the residue, heat to boiling, cool, and filter. To the filtrate add 0.5 mL of hy-drochloric acid: the solution responds to Qualitative Tests <1.09> for sulfate. Separately, to 0.1 g of Dihydroergotamine Mesilate add 5 mL of dilute hydrochloric acid, shake for 5 minutes, filter, and to the filtrate add 1 mL of barium chlo-ride TS: the solution is clear. Determine the absorption spectrum of a solution of Dihydroergotamine Mesilate in methanol (1 in 20,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Di-hydroergotamine Mesilate, previously dried, as directed in the potassium bromide disk method under Infrared Spectro-photometry <2.25>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: －16.7 – －22.79[0.5 g, calcu-lated on the dried basis, a mixture of ethanol (99.5), chlo-roform and ammonia solution (28) (10:10:1), 20 mL, 100 mm]. pH <2.54> Dissolve 0.05 g of Dihydroergotamine Mesilate in 50 mL of water: the pH of this solution is between 4.4 and 5.4.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.10 g of Dihydroergotamine Mesilate in 0.1 mL of a solution of ‌860 methanesulfonic acid (7 in 100) and 50 mL of water: the solution is clear, and has no more color than the following control solutions [1] or [2]. Control solution [1]: Pipet 0.6 mL of Iron (III) Chloride CS and 0.15 mL of Cobalt (II) Chloride CS, mix, and add diluted hydrochloric acid (1 in 40) to make exactly 100 mL. Control solution [2]: Pipet 0.6 mL of Iron (III) Chloride CS, 0.25 mL of Cobalt (II) Chloride CS and 0.1 mL of Cop-per (II) Sulfate CS, mix, and add diluted hydrochloric acid (1 in 40) to make exactly 100 mL. Related substances—Conduct this procedure without exposure to light, using light-resistant vessels. Dissolve 0.10 g of Dihydroergotamine Mesilate in 5 mL of a mixture of chloroform and methanol (9:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of chloroform and methanol (9:1) to make exactly 200 mL, and use this solution as the standard solution (1). Pipet 10 mL of the standard solution (1), add a mixture of chloroform and methanol (9:1) to make exactly 25 mL, and use this solution as the standard solution (2). Perform the test with these solutions as directed under Thin-layer Chro-matography <2.03>. Spot 5 mL each of the sample solution and standard solutions (1) and (2) on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of dichloromethane, ethyl acetate, methanol and ammonia solution (28) (50:50:6:1) to a distance of about 15 cm, and dry the plate with cold wind within 1 minute. Develop the plate again immediately with a freshly prepared mixture of dichloromethane, ethyl acetate, methanol and ammonia so-lution (28) (50:50:6:1) to a distance of about 15 cm, and air-dry the plate. Spray evenly 4-dimethylaminobenzaldehyde TS for spraying on the plate, and dry the plate with warm wind: the spots other than the principal spot obtained from the sample s…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Dihydroergotamine Mesilate, dissolve in 170 mL of a mixture of acetic anhydride and acetic acid (100) (10:1), and titrate <2.50> with 0.02 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.02 mol/L perchloric acid VS ＝ 13.60 mg of C33H37N5O5.CH4O3S
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

dilazep-hydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: ‌Dilazep Hydrochloride Hydrate
  ja: ジラゼプ塩酸塩水和物
monograph id: JP18-dilazep-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C31H44N2O10.2HCl.H2O
molecular weight: 695.63
appearance:
  en: Dilazep Hydrochloride Hydrate occurs as a white crystalline powder. It is odorless. It is freely soluble in acetic acid (100) and in chloroform, soluble in water, slightly soluble in ethanol (95) and in acetic anhydride, and practically insoluble in diethyl ether. Melting point: 200 – 2049C Immerse the sample in a bath of 1109C, and raise the temperature at the rate of about 39C per minute from 1409C to 1509C, about 109C per minute from 1609C to 1959C and about 19C per minute from 1959C. trum: both spectra exhibit similar intensities of absorption at the same wave numbers. pH <2.54> Dissolve 1.0 g of Dilazep Hydrochloride Hy-drate in 100 mL of water: the pH of this solution is between 3.0 and 4.0.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of a solution of Dilazep Hy-drochloride Hydrate (1 in 100) add 0.1 mL of a solution of hydroxylammonium chloride (1 in 10) and 0.1 mL of 8 mol/L potassium hydroxide TS, and warm in a water bath of 709C for 10 minutes. After cooling, add 0.5 mL of dilute hydrochloric acid and 0.1 mL of iron (III) chloride TS: a purple color develops.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Dilazep Hydrochloride Hydrate in 20 mL of water: the solution is clear and colorless. Sulfate <1.14>—Perform the test with 0.5 g of Dilazep Hydrochloride Hydrate. Prepare the control solu-tion with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.048z). Heavy metals <1.07>—Proceed with 2.0 g of Dilazep Hydrochloride Hydrate according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Dilazep Hydrochloride Hydrate according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.40 g of Dilazep Hy-drochloride Hydrate in 10 mL of chloroform, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add chloroform to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatogra-phy <2.03>. Spot 5 mL each of the sample solution and stand-ard solution on a plate of silica gel for thin-layer chroma-tography. Develop the plate with a mixture of methanol, ethyl acetate, dichloromethane and hydrochloric acid (500:200:100:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly Dragendorff's TS for spraying on the plate: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> 2.0 – 3.0z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.3 g of Dilazep Hydrochlo-ride Hydrate, dissolve in 40 mL of a mixture of acetic anhy-dride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 33.88 mg of C H N O .2HCl 31 44 2 10 Identification (1) To 1 mL of a solution of Dilazep Hy-drochloride Hydrate (1 in 100) add 0.1 mL of a solution of hydroxylammonium chloride (1 in 10) and 0.1 mL of 8 mol/L potassium hydroxide TS, and warm in a water bath of 709C for 10 minutes. After cooling, add 0.5 mL of dilute hydrochloric acid and 0.1 mL of iron (III) chloride TS: a purple color develops.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

diltiazem-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Diltiazem Hydrochloride
  ja: ジルチアゼム塩酸塩
monograph id: JP18-diltiazem-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C22H26N2O4S.HCl
molecular weight: 450.98
appearance:
  en: Diltiazem Hydrochloride occurs as white, crys-tals or crystalline powder. It is odorless. It is very soluble in formic acid, freely soluble in water, in methanol and in chloroform, sparingly soluble in aceto-nitrile, slightly soluble in acetic anhydride and in ethanol (99.5), and practically insoluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.05 g of Diltiazem Hydro-chloride in 1 mL of 1 mol/L hydrochloric acid TS, add 2 mL of ammonium thiocyanate-cobalt (II) nitrate TS and 5 mL of chloroform, shake well, and allow to stand: a blue color de-velops in the chloroform layer. Proceed as directed under Oxygen Flask Combustion Method <1.06> with 0.03 g of Diltiazem Hydrochloride, using 20 mL of water as the absorbing liquid, and prepare the test solution: the test solution responds to Qualitative Tests <1.09> (1) for sulfate. Dissolve 0.01 g of Diltiazem Hydrchloride in 0.01 mol/L hydrochloric acid TS to make 100 mL. To 2 mL of the solution add 0.01 mol/L hydrochloric acid TS to make 20 mL. Determine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dil-tiazem Hydrochloride, previously dried, as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>: it exhibits absorption at the wave numbers of about 1741 cm－1, 1678 cm－1, 1252 cm－1 and 1025 cm－1. A solution of Diltiazem Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> (2) for chloride. D Optical rotation <2.49> [a]20: ＋115 – ＋1209(after drying, 0.20 g, water, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Diltiazem Hydrochloride in 20 mL of water: the solution is clear and colorless. Sulfate <1.14>—Perform the test with 1.0 g of Diltia-zem Hydrochloride. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.024z). Heavy metals <1.07>—Proceed with 2.0 g of Diltia- zem Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Place 1.0 g of Diltiazem Hydrochlo- ride in a decomposition flask, add 5 mL of nitric acid and 2 mL of sulfuric acid, put a small funnel on the neck of the flask, and heat cautiously until white fumes are evolved. After cooling, add 2 mL of nitric acid, heat, and repeat this procedure twice, add several 2-mL portions of hydrogen peroxide (30), and heat until the solution becomes colorless to pale yellow. After cooling, add 2 mL of saturated solution of ammonium oxalate monohydrate, and heat again until white fumes are evolved. After cooling, add water to make 5 mL, use this solution as the test solution, and perform the test: the test solution has no more color than the following control solution (not more than 2 ppm). Control solution: Proceed in the same manner as the test solution without Diltiazem Hydrochloride, add 2.0 mL of Standard Arsenic Solution and water to make 5 mL, and proceed in the same manner as the test solution. Related substances—Dissolve 50 mg of Diltiazem Hy-drochloride in 50 mL of diluted ethanol (4 in 5), and use this solution as the sample solution. Measure exactly 1 mL of the sample solution, add diluted ethanol (4 in 5) to make exactly 200 mL, and use this solution as the standard solution. Per-form the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatog-raphy <2.01> according to the following conditions. Deter-mine each peak area of both solutions by automatic integra-tio…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.7 g of Diltiazem Hydro-chloride, previously dried, dissolve in 2.0 mL of formic acid, add 60 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 45.10 mg of C22H26N2O4S.HCl
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

dilute-hydrochloric-acid
type: ChemicalDrugMonograph
pref label:
  en: Dilute Hydrochloric Acid
  ja: 希塩酸
monograph id: JP18-dilute-hydrochloric-acid
publisher: JP
status: Official
version: 18
definition:
  en: Dilute Hydrochloric Acid contains not less than 9.
appearance:
  en: Dilute Hydrochloric Acid is a colorless liquid. It is odorless and has a strong acid taste. Specific gravity d 20: about 1.05.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: A solution of Dilute Hydrochloric Acid (1 in 30) changes blue litmus paper to red and responds to Quali-tative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Sulfate—To 3.0 mL of Dilute Hydrochloric Acid add 5 mL of water and 5 drops of barium chloride TS, and allow to stand for 1 hour: no turbidity is produced. Sulfite—To 3.0 mL of Dilute Hydrochloric Acid add 5 mL of water and 1 drop of iodine TS: the color of iodine TS does not disappear. Bromide or iodide—Place 10 mL of Dilute Hydro-chloric Acid in a glass-stoppered test tube, add 1 mL of chlo- ‌1112‌ roform and 1 drop of 0.002 mol/L potassium permanganate VS, and shake well: the chloroform layer remains colorless. Bromine or chlorine—Place 10 mL of Dilute Hydro-chloric Acid in a glass-stoppered test tube, add 5 drops of potassium iodide TS and 1 mL of chloroform, and shake for 1 minute: the chloroform layer remains free from a purple color. Heavy metals <1.07>—Evaporate 9.5 mL of Dilute Hydrochloric Acid on a water bath to dryness, add 2 mL of dilute acetic acid and water to make 50 mL, and perform the test using this solution as the test solution. Prepare the con-trol solution as follows: to 3.0 mL of Standard Lead Solu-tion add 2 mL of dilute acetic acid and water to make 50 mL (not more than 3 ppm). Arsenic <1.11>—Prepare the test solution with 4.0 mL of Dilute Hydrochloric Acid according to Method 1, and perform the test (not more than 0.5 ppm). Mercury—Dilute 80 mL of Dilute Hydrochloric Acid with water to make exactly 100 mL, and use this solution as the sample solution. Perform the test with the sample solu-tion as directed under Atomic Absorption Spectrophotome-try <2.23> (cold vapor type). Place the sample solution in a sample bottle of the atomic absorption spectrophotometer, add 10 mL of tin (II) chloride-sulfuric acid TS, connect the bottle immediately to the spectrophotometer, circulate air, and determine the absorbance AT of the sample solution after the recorder reading has risen rapidly and become con-stant at a wavelength of 253.7 nm. On the other hand, to 8 mL of Standard Mercury Solution add water to make exactly 100 mL, and determine the abso…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Measure exactly 10 mL of Dilute Hydrochloric Acid, and dilute with 20 mL of water. Titrate <2.50> with 1 mol/L sodium hydroxide VS (indicator: 2 to 3 drops of methyl red TS). Each mL of 1 mol/L sodium hydroxide VS ＝ 36.46 mg of HCl
storage conditions:
  en: Containers—Tight containers.

dilute-iodine-tincture
type: ChemicalDrugMonograph
pref label:
  en: Dilute Iodine Tincture
  ja: 希ヨードチンキ
monograph id: JP18-dilute-iodine-tincture
publisher: JP
status: Official
version: 18
definition:
  en: Dilute Iodine Tincture contains not less than 2.
appearance:
  en: Dilute Iodine Tincture is a dark red-brown liq-uid, and has a characteristic odor. Specific gravity d 20: about 0.93
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To a mixture of 1 mL of starch TS and 9 mL of water add 1 drop of Dilute Iodine Tincture: a dark blue-purple color develops. (2) Evaporate 3 mL of Diluted Iodine Tincture to dry-ness on a water bath, and heat gently over a free flame: a white residue is formed which responds to the Qualitative Tests <1.09> for potassium salt and iodide. Alcohol number <1.01> Not less than 6.7 (Method 2). Per-form the pretreatment (ii) in the Method 1.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Iodine—Pipet exactly 10 mL of Dilute Iodine Tincture, add 0.5 g of potassium iodide, 20 mL of water and 1 mL of dilute hydrochloric acid, and titrate <2.50> with 0.1 mol/L sodium thiosulfate VS (indicator: 2 mL of starch TS). Each mL of 0.1 mol/L sodium thiosulfate VS ＝ 12.69 mg of I (2) Potassium iodide—Pipet 10 mL of Dilute Iodine Tincture into an iodine flask, add 20 mL of water, 50 mL of hydrochloric acid and 5 mL of chloroform. Cool to room temperature, and titrate <2.50> with 0.05 mol/L potassium iodate VS until the red-purple color in the chloroform layer disappears while agitating vigorously and continuously. After the chloroform layer has been decolorized, allow the mixture to stand for 5 minutes. If the color reappears, the mixture should be titrated <2.50> further with 0.05 mol/L potassium iodate VS. Calculate the amount (mg) of potas-sium iodide from the volume (a mL) of 0.05 mol/L potas-sium iodate VS consumed as above and the volume ( b mL) of 0.1 mol/L sodium thiosulfate VS consumed in the titra-tion under Assay (1). Amount (mg) of potassium iodide (KI) ＝ 16.60 ×{a － (b/2)}
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dimemorfan-phosphate
type: ChemicalDrugMonograph
pref label:
  en: Dimemorfan Phosphate
  ja: ジメモルファンリン酸塩
monograph id: JP18-dimemorfan-phosphate
publisher: JP
status: Official
version: 18
molecular formula: C18H25N.H3PO4
molecular weight: 353.39
definition:
  en: Dimemorfan Phosphate, when dried, contains not less than 98.
appearance:
  en: Dimemorfan Phosphate occurs as white to pale yellow-white, crystals or crystalline powder. It is freely soluble in acetic acid (100), sparingly soluble in water and in methanol, slightly soluble in ethanol (95), and practically insoluble in diethyl ether. Melting point: about 2659C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Dimemorfan Phosphate (1 in 5000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dimemorfan Phosphate, previously dried, as directed in the potassium bromide disk method under Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibits similar intensities of absorption at the same wave numbers. To 2 mL of a solution of Dimemorfan Phosphate (1 in 100) add 2 to 3 drops of silver nitrate TS: a yellow precipi-tate is formed, and it dissolves on the addition of dilute nitric acid. D Optical rotation <2.49> [a]20: ＋25 – ＋279(after drying, 1 g, methanol, 100 mL, 100 mm). pH <2.54> Dissolve 1.0 g of Dimemorfan Phosphate in 100 mL of water: the pH of this solution is between 4.0 and 5.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Dimemorfan Phosphate according to Method 1, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Dimemorfan Phosphate according to Method 3, and per-form the test. Use 10 mL of a solution of magnesium nitrate hexahydrate in ethanol (95) (1 in 10) (not more than 2 ppm). Related substances—Dissolve 0.10 g of Dimemorfan Phosphate in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of methanol, chloroform and am-monia solution (28) (150:150:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly the plate with Dragen-dorff's TS for spraying: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Dimemorfan Phos-phate, previously dried, dissolve in 100 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 35.34 mg of C18H25N.H3PO4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dimenhydrinate
type: ChemicalDrugMonograph
pref label:
  en: Dimenhydrinate
  ja: ジメンヒドリナート
monograph id: JP18-dimenhydrinate
publisher: JP
status: Official
version: 18
molecular formula: NO
molecular weight: 255.36
definition:
  en: Dimenhydrinate, when dried, contains not less than 53.
appearance:
  en: Dimenhydrinate occurs as a white crystalline powder. It is odorless, and has a bitter taste. It is very soluble in chloroform, freely soluble in ethanol (95), and slightly soluble in water and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 0.5 g of Dimenhydrinate in 30 mL of dilute ethanol, add 30 mL of water, and use this solu-tion as the sample solution. Transfer 30 mL of the sample solution to a separator, and add 2 mL of ammonia solution (28). Extract with two 10-mL portions of diethyl ether, com-bine the diethyl ether extracts, wash the combined extracts with 5 mL of water, and then extract the combined extracts with 15 mL of diluted hydrochloric acid (1 in 100). With this acid extract perform the following tests. To 5 mL of this acid extract add 5 drops of Reinecke salt TS: a light red precipitate is produced. To 10 mL of this acid extract add 10 mL of 2,4,6-trinitrophenol TS dropwise, and allow to stand for 30 minutes. Collect the precipitate by filtrating, recrystallize from dilute ethanol, and dry at 1059C for 30 minutes: the crystals melt <2.60> between 1289C and 1339C. To 30 mL of the sample solution obtained in (1) add 2 mL of dilute sulfuric acid, and cool for 30 minutes. Scratch the inside wall of the container frequently to facilitate crystallization. Filter, and wash the white crystals with a small amount of ice-cooled water. Dry the crystals for 1 hour at 1059C: the crystals melt <2.60> between 3009C and 3059C with decomposition. To 0.01 g of the crystals obtained in (2) add 10 drops of hydrogen peroxide TS and 1 drop of hydrochloric acid, and evaporate on a water bath to dryness: the residue shows a yellow-red color. When the dish containing the residue is held over a vessel containing 2 to 3 drops of ammonia TS, the color changes to red-purple, which is discharged on the addition of 2 to 3 drops of sodium hydroxide TS. Mix well 0.05 g of the crystals obtained in (2) with 0.5 g of sodium peroxide in a nickel crucible, and heat until the mass melts. Cool, dissolve the melted mass in 20 mL of water, and acidify with dilute nitric acid: the solution re-sponds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Chloride <1.03>—Transfer 50 mL of the fil-trate obtained in the Assay (2) to a Nessler tube, add 1 mL of nitric acid, and allow to stand for 5 minutes: the turbidity of the solution is not greater than that of the following control ether extracts, and wash the combined diethyl ether extracts with three 50-mL portions of water. To the diethyl ether ex-tracts add exactly 25 mL of 0.05 mol/L sulfuric acid VS, and add 25 mL of water. Shake thoroughly, and evaporate the diethyl ether gently. Cool, and titrate the excess sulfuric acid with 0.1 mol/L sodium hydroxide VS (indicator: 3 drops of methyl red TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.05 mol/L sulfuric acid VS ＝ 25.54 mg C17H21NO (2) 8-Chlorotheophylline—Weigh accurately about 0.8 g of Dimenhydrinate, previously dried, transfer to a 200-mL volumetric flask, add 50 mL of water, 3 mL of ammonia TS and 6 mL of a solution of ammonium nitrate (1 in 10), and heat on a water bath for 5 minutes. Add exactly 25 mL of 0.1 mol/L silver nitrate VS, heat on a water bath for 15 minutes with occasional shaking, cool, and add water to make exactly 200 mL. Allow to stand overnight to settle the precipitate, and filter through a dry filter paper, discarding the first 20 mL of the filtrate. Measure exactly 100 mL of the subsequent filtrate, acidify with nitric acid, add 3 mL of nitric acid, and titrate the excess silver nitrate with 0.1 mol/L ammonium thiocyanate VS (indicator: 2 mL of ammonium iron (III) sulfate TS). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L silver nitrate VS ＝ 21.46 mg of C7H7ClN4O2
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: (1) Diphenhydramine—Weigh accurately about 0.5 g of Dimenhydrinate, previously dried, transfer to a 250-mL separator, and add 50 mL of water, 3 mL of ammo- mine (C 17H21 NO: 255.36), and not less than 44.0z nia TS and 10 g of sodium chloride. Extract with six 15-mL portions of diethyl ether with shaking, combine the diethyl and not more than 47.0z of 8-chlorotheophylline (C7H7ClN4O2: 214.61). Description Dimenhydrinate occurs as a white crystalline powder. It is odorless, and has a bitter taste. It is very soluble in chloroform, freely soluble in ethanol (95), and slightly soluble in water and in diethyl ether. Identification (1) Dissolve 0.5 g of Dimenhydrinate in 30 mL of dilute ethanol, add 30 mL of water, and use this solu-tion as the sample solution. Transfer 30 mL of the sample solution to a separator, and add 2 mL of ammonia solution (28). Extract with two 10-mL portions of diethyl ether, com-bine the diethyl ether extracts, wash the combined extracts with 5 mL of water, and then extract the combined extracts with 15 mL of diluted hydrochloric acid (1 in 100). With this acid extract perform the following tests. To 5 mL of this acid extract add 5 drops of Reinecke salt TS: a light red precipitate is produced. To 10 mL of this acid extract add 10 mL of 2,4,6-trinitrophenol TS dropwise, and allow to stand for 30 minutes. Collect the precipitate by filtrating, recrystallize from dilute ethanol, and dry at 1059C for 30 minutes: the crystals melt <2.60> between 1289C and 1339C. To 30 mL of the sample solution obtained in (1) add 2 mL of dilute sulfuric acid, and cool for 30 minutes. Scratch the inside wall of the container frequently to facilitate crystallization. Filter, and wash the white crystals with a small amount of ice-cooled water. Dry the crystals for 1 hour at 1059C: the crystals melt <2.60> between 3009C and 3059C with decomposition. To 0.01 g of the crystals obtained in (2) add 10 drops of hydrogen peroxide TS and 1 drop of hydrochloric acid, and evapor…
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

dimercaprol
type: ChemicalDrugMonograph
pref label:
  en: Dimercaprol
  ja: ジメルカプロール
monograph id: JP18-dimercaprol
publisher: JP
status: Official
version: 18
molecular formula: C3H8OS2
molecular weight: 124.23
definition:
  en: Dimercaprol contains not less than 98.
appearance:
  en: Dimercaprol is a colorless or pale yellow liq-uid. It has a mercaptan-like, disagreeable odor. It is miscible with methanol and with ethanol (99.5) It is soluble in peanut oil, and sparingly soluble in water. It shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Add 1 drop of Dimercaprol to a mix-ture of 1 drop of a solution of cobalt (II) chloride hexahy-drate (1 in 200) and 5 mL of water: a yellow-brown color de-velops. (2) Determine the infrared absorption spectrum of Dimercaprol as directed in the liquid film method under In-frared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wave numbers. D Refractive index <2.45> n20: 1.570 – 1.575 Specific gravity <2.56> d 20: 1.238 – 1.248
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 mL of Dimercaprol in 20 mL of peanut oil: the solution is clear and colorless to pale yellow. Bromide—To 2.0 g of Dimercaprol add 25 mL of dilute potassium hydroxide-ethanol TS, and heat in a water bath under a reflux condenser for 2 hours. Evaporate the ethanol in a current of warm air, add 20 mL of water, and cool. Add a mixture of 10 mL of hydrogen peroxide (30) and 17 21 7 7 4 2 40 mL of water, boil gently under a reflux condenser for 10 ethanol (95), and heat with swirling on a water bath until the solution just boils. Continue to heat for 30 seconds, and filter through a glass filter (G4). Wash the filter with warm ethanol (95), transfer the filtrate and washings to a flask, and evaporate the ethanol on a water bath to make 5 mL. Add 50 mL of water, 3 mL of ammonia TS and 6 mL of a solution of ammonium nitrate (1 in 10), heat the mixture on a water bath for 5 minutes, add exactly 25 mL of 0.1 mol/L silver nitrate VS, and heat on a water bath for 15 minutes with occasional shaking. Transfer the mixture to a 200-mL volumetric flask, using water to rinse the flask, cool, add water to make exactly 200 mL, and proceed as directed in the Assay (2) under Dimenhydrinate. Each mL of 0.1 mol/L silver nitrate VS ＝ 47.00 mg of C17H21NO.C7H7ClN4O2
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.15 g of Dimercaprol into a glass-stoppered flask, dissolve in 10 mL of methanol, and titrate <2.50> immediately with 0.05 mol/L iodine VS until a pale yellow color is produced. Perform a blank determina-tion in the same manner, and make any necessary correction. Each mL of 0.05 mol/L iodine VS ＝ 6.212 mg of C3H8OS2
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

dimorpholamine
type: ChemicalDrugMonograph
pref label:
  en: Dimorpholamine
  ja: ジモルホラミン
monograph id: JP18-dimorpholamine
publisher: JP
status: Official
version: 18
molecular formula: C20H38N4O4
molecular weight: 398.54
cas number: 119-48-2
definition:
  en: Dimorpholamine, when dried, contains not less than 98.
appearance:
  en: Dimorpholamine is a white to light yellow, crystalline powder, masses or syrupy liquid. It is very soluble in ethanol (99.5) and in acetic anhydride, and soluble in water. The pH of a solution prepared by dissolving 1.0 g of Dimorpholamine in 10 mL of water is between 6.0 and 7.0. It is hygroscopic.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Dimorpholamine (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave-lengths. (2) Determine the infrared absorption spectrum of Dimorpholamine, previously dried, as directed in the potas-sium bromide disk method under the Infrared Spectropho-tometry <2.25>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Dimorpholamine in 50 mL of water: the solution is clear and colorless to pale yellow. Chloride <1.03>—To 20 mL of the solution obtained in (1) add 6 mL of dilute nitric acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution with 0.40 mL of 0.01 mol/L hy-drochloric acid VS (not more than 0.036z). Sulfate <1.14>—To 10 mL of the solution obtained in add 1 mL of dilute hydrochloric acid and water to make 50 mL. Perform the test using this solution as the test solu-tion. Prepare the control solution with 0.40 mL of 0.005 mol/L sulfuric acid VS (not more than 0.096z). Heavy metals <1.07>—Proceed with 2.0 g of Dimor- pholamine according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 0.20 g of Dimorphola-mine in 10 mL of ethanol (99.5), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add ethanol (99.5) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solu-tion on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of ethanol (99.5) and water (4:1) to a distance of about 10 cm, and air-dry the plate. Allow the plate to stand in iodine vapor for 10 minutes: the spot other than the principal spot obtained from the sample solution is not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, in vacu-um, phosphorus (V) oxide, 8 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Dimorpholamine, previously dried, dissolve in 50 mL of acetic anhydride, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 39.85 mg of C20H38N4O4
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

dinoprost
type: ChemicalDrugMonograph
pref label:
  en: Dinoprost
  ja: ジノプロスト
monograph id: JP18-dinoprost
publisher: JP
status: Official
version: 18
molecular formula: C20H34O5
molecular weight: 354.48
definition:
  en: Dinoprost contains not less than 98.
appearance:
  en: Dinoprost occurs as white, waxy masses or powder, or a clear, colorless to light yellow and viscous liquid. It is odorless. It is very soluble in N,N-dimethylformamide, freely solu-ble in methanol, in ethanol (99.5) and in diethyl ether, and very slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 5 mg of Dinoprost add 2 mL of sul-furic acid, and dissolve by shaking for 5 minutes: a dark red color develops. To this solution add 30 mL of sulfuric acid: an orange color develops with a green fluorescence. Dissolve 1 mg of Dinoprost in 50 mL of diluted sulfu-ric acid (7 in 10), and warm in a water bath warmed at 509C for 40 minutes. After cooling, determine the absorption spectrum of the solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi-ties of absorption at the same wavelengths. Amount (mg) of dimorpholamine (C ＝ MS × QT/QS × 1/5 20H38N4O4) Warm Dinoprost at 409C to effect a liquid, and de-termine the infrared absorption spectrum of the liquid as directed in the liquid film method under Infrared Spectro- MS: Amount (mg) of dimorpholamine for assay taken Internal standard solution—A solution of butyl parahy-droxybenzoate in acetonitrile (1 in 25,000). Operating conditions— photometry <2.25>, and compare the spectrum with the Ref- erence Spectrum: both spectra exhibits similar intensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋24 – ＋319(0.2 g, ethanol Detector: An ultraviolet absorption photometer (wave- (99.5), 10 mL, 100 mm). ‌870
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.20 g of Dinoprost in 5 mL of ethanol (99.5): the solution is clear and colorless to pale yellow. (2) Related substances—Dissolve 10 mg of Dinoprost in 2 mL of methanol, add water to make 10 mL, and use this solution as the sample solution. Pipet 3 mL of the sample so-lution, add diluted methanol (1 in 5) to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of these solutions by the automatic integration method: the total area of the peaks other than dinoprost ob-tained from the sample solution is not larger than the peak area of dinoprost from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 205 nm). Column: A stainless steel column about 5 mm in inside di-ameter and about 15 cm in length, packed with octadecyl-silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of 0.02 mol/L potassium dihy-drogenphosphate TS and acetonitrile (5:2). Flow rate: Adjust so that the retention time of dinoprost is about 20 minutes. Selection of column: Dissolve 0.01 g each of isopropyl parahydroxybenzoate and propyl parahydroxybenzoate in 2 mL of methanol, and add water to make 10 mL. To 1 mL of this solution add diluted methanol (1 in 5) to make 30 mL, proceed with 10 mL of this solution under the above operat-ing conditions, and calculate the resolution. Use a column giving elution of isopropyl parahydroxybenzoate and propyl parahydroxybenzoate in this order with the resolution be-tween these peaks being not less than 2.5. Detection sensitivity: Adjust the detection sensitivity so that the peak height of dinoprost from the standard solution composes 5z to 15z of the fu…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 50 mg of Dinoprost, dis-solve in 30 mL of N,N-dimethylformamide, and titrate <2.50> with 0.02 mol/L tetramethylammonium hydroxide VS under a stream of nitrogen (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.02 mol/L tetramethylammonium hydroxide VS Diphenhydramine
type: PharmacopoeiaMonograph

diphenhydramine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Diphenhydramine Hydrochloride
  ja: ジフェンヒドラミン塩酸塩
monograph id: JP18-diphenhydramine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C17H21NO.HCl
molecular weight: 291.82
cas number: 147-24-0
appearance:
  en: Diphenhydramine Hydrochloride occurs as white, crystals or crystalline powder. It is odorless, and has a bitter taste, followed by a sensation of numbness on the ton-gue. It is very soluble in methanol and in acetic acid (100), freely soluble in water and in ethanol (95), sparingly soluble in acetic anhydride, and practically insoluble in diethyl ether. It is gradually affected by light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Diphenhydramine Hydrochloride in methanol (1 in 2000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Dipenhydramine Hydrochloride as directed in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Diphenhydramine Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Diphenhydramine Hydrochlo-ride in 10 mL of water: the pH of this solution is between 4.0 and 5.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Diphenhydramine Hydrochloride in 10 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of Diphen- hydramine Hydrochloride according to Method 4, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances—Dissolve 0.20 g of Diphenhydra-mine Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample so-lution, add methanol to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Diphenhydramine Hydrochloride, previously dried, dissolve in 50 mL of a mix-ture of acetic anhydride and acetic acid (100) (7:3). Titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS [147-24-0] ＝ 29.18 mg of C 17H 21NO.HCl Diphenhydramine Hydrochloride, when dried, contains not less than 98.0z of diphenhydramine hydrochloride (C17H21NO.HCl). Description Diphenhydramine Hydrochloride occurs as white, crystals or crystalline powder. It is odorless, and has a bitter taste, followed by a sensation of numbness on the ton-gue. It is very soluble in methanol and in acetic acid (100), freely soluble in water and in ethanol (95), sparingly soluble in acetic anhydride, and practically insoluble in diethyl ether. It is gradually affected by light. Identification (1) Determine the absorption spectrum of a solution of Diphenhydramine Hydrochloride in methanol (1 in 2000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab-sorption at the same wavelengths. Determine the infrared absorption spectrum of Dipenhydramine Hydrochloride as directed in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Diphenhydramine Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Diphenhydramine Hydrochlo-ride in 10 mL of water: the pH of this solution is between 4.0 and 5.0. Melting point <2.60> 166 – 1709C Purity (1) Clarity and color of solution—Dissolve 1.0 g of Diphenhydramine Hydrochloride in 10 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 1…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

diphenhydramine-tannate
type: ChemicalDrugMonograph
pref label:
  en: Diphenhydramine Tannate
  ja: タンニン酸ジフェンヒドラミン
monograph id: JP18-diphenhydramine-tannate
publisher: JP
status: Official
version: 18
appearance:
  en: Diphenhydramine Tannate occurs as a grayish white to light brown powder. It is odorless or has a slight, characteristic odor. It is tasteless. It is slightly soluble in ethanol (95), and practically insolu-ble in water and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 g of Diphenhydramine Tannate add 15 mL of water and 0.3 mL of dilute hydrochloric acid, shake thoroughly for 1 minute, filter, and use this filtrate as the sample solution. Transfer 10 mL of the sample solution to a separator, extract with two 20-mL portions of chlo-roform, combine the chloroform extracts, and evaporate on a water bath to dryness. To 5 mL of a solution of the residue (1 in 100) add 5 drops of Reinecke salt TS: a light red pre-cipitate is produced. To 10 mL of a solution of the residue obtained in (1) (1 in 100) add 10 mL of 2,4,6-trinitrophenol TS dropwise, and allow to stand for 30 minutes. Collect the precipitate by filtration, recrystallize from dilute ethanol, and dry at 1059C for 30 minutes: the crystals melt <2.60> between 1289C and 1339C. To 1 mL of the sample solution obtained in (1) add 1 drop of iron (III) chloride TS: a dark blue-purple color de-velops.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: Heavy metals <1.07>—Proceed with 1.0 g of Diphenhydramine Tannate according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Loss on drying <2.41> Not more than 7.0z (1 g, 1059C, 5 hours). Residue on ignition <2.44> Not more than 1.0z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Transfer about 1.7 g of Diphenhydramine Tannate, accurately weighed, to a separator, dissolve in 20 mL of water and 3.0 mL of dilute hydrochloric acid with thorough shaking, add 20 mL of a solution of sodium hydroxide (1 in 10) and exactly 25 mL of isooctane, shake vigorously for 5 minutes, dissolve 2 g of sodium chloride with shaking, and allow to stand. To 20 mL of the isooctane layer add exactly 80 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same manner, and make any nec-essary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 25.54 mg of C17H21NO
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.

diphenhydramine
type: ChemicalDrugMonograph
pref label:
  en: Diphenhydramine
  ja: ジフェンヒドラミン
monograph id: JP18-diphenhydramine
publisher: JP
status: Official
version: 18
molecular formula: C17H21NO
molecular weight: 255.35
definition:
  en: Diphenhydramine contains not less than 96.
appearance:
  en: Diphenhydramine is a clear, light yellow to yellow liquid. It has a characteristic odor, and has a burning taste at first, followed by a slight sensation of numbness on the tongue. It is miscible with acetic anhydride, with acetic acid (100), with ethanol (95) and with diethyl ether. D It is very slightly soluble in water. It is gradually affected by light. Refractive index n20: about 1.55 Boiling point: about 1629C (in vacuum, 0.67 kPa).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 50 mg of Diphenhydramine add 2 mL of sulfuric acid: an orange-red precipitate is produced immediately, and its color changes to red-brown on stand-ing. Add carefully 2 mL of water to this solution: the inten-sity of the color changes, but the color tone does not change. (2) Dissolve 0.1 g of Diphenhydramine in 10 mL of dilute ethanol, add an excess of a saturated solution of 2,4,6-trinitrophenol in dilute ethanol with stirring, and cool in ice. Collect the produced crystals, recrystallize from dilute ethanol, and dry at 1059C for 30 minutes: the crystals melt <2.60> between 1289C and 1339C. Specific gravity <2.56> d 20: 1.013 – 1.020
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) b-Dimethylaminoethanol—Dissolve 1.0 g of Diphenhydramine in 20 mL of diethyl ether, and extract with two 10-mL portions of water with thorough shaking. Com-bine the water extracts, and add 2 drops of phenolphthalein TS and 1.0 mL of 0.05 mol/L sulfuric acid VS: no red color develops. Benzohydrol—Transfer 1.0 g of Diphenhydramine to a separator, dissolve in 20 mL of diethyl ether, and extract with two 25-mL portions of diluted hydrochloric acid (1 in 15) with thorough shaking. Separate the diethyl ether layer, evaporate slowly on a water bath, and dry in a desiccator (in vacuum, silica gel) for 2 hours: the mass of the residue is not more than 20 mg. ＝ 7.090 mg of C 20H 34O5 Heavy metals <1.07>—Proceed with 1.0 g of Diphen- hydramine according to Method 2, and perform the test.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Diphenhydramine, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. ‌JP XVIII Official Monographs / Diphenhydramine and Bromovalerylurea Powder 871‌ Each mL of 0.1 mol/L perchloric acid VS ＝ 25.54 mg of C17H21NO
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant, and in a place not exceeding
type: PharmacopoeiaMonograph

diphtheria-toxoid
type: ChemicalDrugMonograph
pref label:
  en: Diphtheria Toxoid
  ja: ジフテリアトキソイド
monograph id: JP18-diphtheria-toxoid
publisher: JP
status: Official
version: 18
appearance:
  en: Diphtheria Toxoid is a clear, colorless to light yellow-brown liquid. Adsorbed Diphtheria Toxoid for Adult Use

dipyridamole
type: ChemicalDrugMonograph
pref label:
  en: Dipyridamole
  ja: ジピリダモール
monograph id: JP18-dipyridamole
publisher: JP
status: Official
version: 18
molecular formula: C24H40N8O4
molecular weight: 504.63
definition:
  en: Dipyridamole, when dried, contains not less than 98.
appearance:
  en: Dipyridamole occurs as yellow, crystals or crystalline powder. It is odorless, and has a slightly bitter taste. It is freely soluble in chloroform, sparingly soluble in methanol and in ethanol (99.5), and practically insoluble in water and in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Dissolve 5 mg of Dipyridamole in 2 mL of sulfuric acid, add 2 drops of nitric acid, and shake: a deep purple color develops. Determine the absorption spectrum of a solution of Dipyridamole in a mixture of methanol and hydrochloric acid (99:1) (1 in 100,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi-ties of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dipyridamole, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Dipyridamole in 10 mL of chloroform: the solution is clear, and shows a yellow color. Heavy metals <1.07>—Proceed with 2.0 g of Dipyridamole according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Dipyridamole according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 50 mg of Dipyridamole in 50 mL of the mobile phase, and use this solution as the sample solution. Pipet 0.5 mL of the sample solution, add the mobile phase to make exactly 100 mL, and use this solu-tion as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the total area of the peaks other than dipyridamole obtained from the sample solution is not larger than the peak area of dipyridamole from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column 4 mm in inside diameter and 15 cm in length, packed with octylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 0.2 g of potassium dihydrogen phosphate in 200 mL of water, and add 800 mL of metha-nol. Flow rate: Adjust so that the retention time of dipyrida-mole is about 4 minutes. Time span of measurement: About 5 times as long as the retention time of dipyridamole. System suitability— Test for required detectability: To exactly 5 mL of the standard solution add the mobile phase to make exactly 25 mL. Confirm that the peak area of dipyridamole obtained with 20 mL of this solution is equivalent to 15 to 25z of that with 20 mL of the stand…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.6 g of Dipyridamole, pre-viously dried, dissolve in 70 mL of methanol, and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Perform a blank determination in the same man-ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 50.46 mg of C24H40N8O4
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

disopyramide
type: ChemicalDrugMonograph
pref label:
  en: Disopyramide
  ja: ジソピラミド
monograph id: JP18-disopyramide
publisher: JP
status: Official
version: 18
molecular formula: C21H29N3O
molecular weight: 339.47
cas number: 3737-09-5
definition:
  en: Disopyramide contains not less than 98.
appearance:
  en: Disopyramide occurs as white, crystals or crys-talline powder. It is very soluble in methanol and in ethanol (95), freely soluble in acetic anhydride, in acetic acid (100) and in diethyl ether, and slightly soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) To 1 mL of a solution of Disopyramide in ethanol (95) (1 in 20) add 10 mL of 2,4,6-trinitrophenol TS, and warm: a yellow precipitate is formed. Filter this pre-cipitate, wash with water, and dry at 1059C for 1 hour: the residue melts <2.60> between 1729C and 1769C. Determine the absorption spectrum of a solution of Disopyramide in 0.05 mol/L sulfuric acid-methanol TS (1 in 25,000) as directed under Ultraviolet-visible Spectropho-tometry <2.24>, and compare the spectrum with the Refer-ence Spectrum: both spectra exhibit similar intensities of ab- pal spot obtained from the sample solution are not more in-tense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (0.5 g, in vacu-um, 809C, 2 hours). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of Disopyramide, dis-solve in 30 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 16.97 mg of C21H29N3O
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

distigmine-bromide
type: ChemicalDrugMonograph
pref label:
  en: Distigmine Bromide
  ja: ジスチグミン臭化物
monograph id: JP18-distigmine-bromide
publisher: JP
status: Official
version: 18
molecular formula: C22H32Br2N4O4
molecular weight: 576.32
cas number: 15876-67-2
definition:
  en: Distigmine Bromide contains not less than 98.
appearance:
  en: Distigmine Bromide occurs as a white crystal-line powder. It is very soluble in water, freely soluble in methanol, in ethanol (95) and in acetic acid (100), and slightly soluble in acetic anhydride. The pH of a solution of Distigmine Bromide (1 in 100) is between 5.0 and 5.5. It is slightly hygroscopic. It is gradually colored by light. Melting point: about 1509C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Distigmine Bromide (1 in 25,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dis-tigmine Bromide as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. To 5 mL of a solution of Distigmine Bromide (1 in 10) add 2 mL of dilute nitric acid: the solution responds to Qualitative Tests <1.09> (1) for bromide.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Dissolve 1.0 g of Dis-opyramide in 10 mL of ethanol (95), and add 2 mL of dilute acetic acid and water to make 50 mL. Perform the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of Standard Lead Solution add 10 mL of ethanol (95), 2 mL of dilute acetic acid and water to make 50 mL (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Disopyramide according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.40 g of Disopyramide in 10 mL of methanol, and use this solution as the sample so-lution. Pipet 1 mL of the sample solution, add methanol to make exactly 400 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatog-raphy. Develop the plate with a mixture of 1-butanol, water and ammonia solution (28) (45:4:1) to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spots other than the princi- Description Distigmine Bromide occurs as a white crystal-line powder. It is very soluble in water, freely soluble in methanol, in ethanol (95) and in acetic acid (100), and slightly soluble in acetic anhydride. The pH of a solution of Distigmine Bromide (1 in 100) is between 5.0 and 5.5. It is slightly hygroscopic. It is gradually colored by light. Melting point: about 1509C (with decomposition). Identification (1) Determine the absorption spectrum of a solution of Distigmine Bromide (1 in 25,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dis-tigmine Bromide as directe…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of Distigmine Bromide, dissolve in 60 mL of a mixture of acetic anhydride and acetic acid (100) (8:1), and titrate <2.50> with 0.1 mol/L ＝ MS × (AT2 － AT1)/(AS2 － AS1) × V?/V × 1/20 MS: Amount (mg) of distigmine bromide for assay taken, calculated on the anhydrous basis Dissolution <6.10> When the test is performed at 75 revolu-tions per minute according to the Paddle method, using 500 mL of water as the dissolution medium, the dissolution rate in 30 minutes of Distigmine Bromide Tablets is not less than 80z. Start the test with 1 tablet of Distigmine Bromide Tablets, withdraw not less than 20 mL of the medium at the specified minute after starting the test, and filter through a membrane filter with a pore size not exceeding 0.8 mm. Discard not less than 10 mL of the first filtrate, pipet V mL of the subsequent filtrate, add water to make exactly V? mL so that each mL contains about 10 mg of distigmine bromide (C22H32Br2N4O 4), and use this solution as the sample solution. Separately, weigh accurately about 50 mg of distigmine bromide for assay (separately determine the water <2.48> in the same manner as Distigmine Bromide), and dissolve in water to make exactly 100 mL. Pipet 10 mL of this solution, add water to make exactly 500 mL, and use this solution as the standard solution. Perform the test with the sample solution and standard solution as directed under Ultraviolet-visible Spectrophotometry <2.24>, and determine the absorbances, AT1 and AS1, at 270 nm, and AT2 and AS2, at 350 nm. Dissolution rate (z) with respect to the labeled amount perchloric acid VS (potentiometric titration with platinum electrode). Perform a blank determination in the same man- of distigmine bromide (C22H32 Br2N4O4) ner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ MS × (AT1 － AT2)/(AS1 － AS2) × V?/V × 1/C × 10 MS: Amount (mg) of distigmine bromide for assay taken, ＝ 28.82 mg of C22H32 Br2N4O4 calculated on the anhydrous basis…
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

disulfiram
type: ChemicalDrugMonograph
pref label:
  en: ‌Disulfiram
  ja: ジスルフィラム
monograph id: JP18-disulfiram
publisher: JP
status: Official
version: 18
molecular formula: C10H20N2S4
molecular weight: 296.54
appearance:
  en: Disulfiram occurs as white to yellowish white, crystals or crystalline powder. It is freely soluble in acetone and in toluene, sparingly soluble in methanol and in ethanol (95), and practically in-soluble in water.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Disulfiram in ethanol (95) (1 in 100,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Disul-firam, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Disulfiram according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Disulfiram according to Method 4, and perform the test (not more than 2 ppm). Diethyldithiocarbamic acid—Dissolve 0.10 g of Dis-ulfiram in 10 mL of toluene, and shake with 10 mL of diluted sodium carbonate TS (1 in 20). Discard the toluene layer, wash the water layer with 10 mL of toluene, shake with 5 drops of a solution of cupric sulfate (1 in 250) and 2 mL of toluene, and allow to stand: no light yellow color de-velops in the toluene layer. Related substances—Dissolve 50 mg of Disulfiram in 40 mL of methanol, add water to make 50 mL, and use this solution as the sample solution. Pipet 1 mL of the sample so-lution, add the mobile phase to make exactly 200 mL, and use this solution as the standard solution. Perform the test with exactly 10 mL each of the sample solution and the stand-ard solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area of both solutions by the automatic integration method: the total area of the peaks other than disulfiram ob-tained from the sample solution is not larger than the peak area of disulfiram from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 210 nm). Column: A stainless steel column about 5 mm in inside di-ameter and about 15 cm in length, packed with octadecyl- silanized silica gel for liquid chromatography (5 mm in parti-cle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of methanol and water (7:3). Flow rate: Adjust so that the retention time of disulfiram is about 8 minutes. Selection of column: Dissolve 50 mg of Disulfiram and 50 mg of benzophenone in 40 mL of methanol, and add water to make 50 mL. To 1 mL of this s…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Disulfiram, previ-ously dried, in an iodine bottle, dissolve in 20 mL of ace-tone, add 1.5 mL of water and 1.0 g of potassium iodide, and dissolve by shaking thoroughly. To this solution add 3.0 mL of hydrochloric acid, stopper the bottle tightly, shake, and allow to stand in a dark place for 3 minutes. Add 70 mL of water, and titrate <2.50> with 0.1 mol/L sodium thiosul-fate VS (potentiometric titration). Perform a blank determi-nation in the same manner, and make any necessary correc-tion. Each mL of 0.1 mol/L sodium thiosulfate VS ＝ 14.83 mg of C10H20N2S4
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

dl-camphor
type: ChemicalDrugMonograph
pref label:
  en: dl-Camphor
  ja: dl-カンフル
monograph id: JP18-dl-camphor
publisher: JP
status: Official
version: 18
molecular formula: H16O
molecular weight: 152.23
definition:
  en: dl-Camphor contains not less than 96.
appearance:
  en: dl-Camphor occurs as colorless or white, translucent crystals, crystalline powder or masses. It has a characteristic, agreeable odor, and has a slightly bitter taste followed by a pleasant, cooling sensation. It is freely soluble in ethanol (95), in diethyl ether and in carbon disulfide, and slightly soluble in water. It slowly volatilizes at room temperature.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: Dissolve 0.1 g of dl-Camphor in 2 mL of methanol, add 1 mL of 2,4-dinitrophenylhydradine TS, and heat for 5 minutes on a water bath: an orange-red precipitate is formed. D Optical rotation <2.49> [a]20: －1.5 – ＋1.59(5 g, ethanol System repeatability: When the test is repeated 6 times with 2 mL of the standard solution under the above operating conditions, the relative standard deviation of the ratios of the peak area of dl-camphor to that of the internal standard is not more than 1.0z.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Water—Shake 1.0 g of d-Camphor with 10 mL of carbon disulfide: the solution is clear. (2) Chlorinated compounds—Mix 0.20 g of finely pow- C10 H16O: 152.23 dered d-Camphor with 0.4 g of sodium peroxide in a dried porcelain crucible. Heat the crucible gently by the open flame until the incineration is complete. Dissolve the residue in 20 mL of warm water, acidify with 12 mL of dilute nitric acid, and filter the solution into a Nessler tube. Wash the (1RS,4RS )-1,7,7-Trimethylbicyclo[2.2.1]heptan-2-one [76-22-2] dl-Camphor contains not less than 96.0z of dl-cam-phor (C10H16O). ‌612 Description dl-Camphor occurs as colorless or white, translucent crystals, crystalline powder or masses. It has a characteristic, agreeable odor, and has a slightly bitter taste followed by a pleasant, cooling sensation. It is freely soluble in ethanol (95), in diethyl ether and in carbon disulfide, and slightly soluble in water. It slowly volatilizes at room temperature. Identification Dissolve 0.1 g of dl-Camphor in 2 mL of methanol, add 1 mL of 2,4-dinitrophenylhydradine TS, and heat for 5 minutes on a water bath: an orange-red precipitate is formed. D Optical rotation <2.49> [a]20: －1.5 – ＋1.59(5 g, ethanol System repeatability: When the test is repeated 6 times with 2 mL of the standard solution under the above operating conditions, the relative standard deviation of the ratios of the peak area of dl-camphor to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.

dl-menthol
type: ChemicalDrugMonograph
pref label:
  en: dl-Menthol
  ja: dl-メントール
monograph id: JP18-dl-menthol
publisher: JP
status: Official
version: 18
molecular formula: C10H20O
molecular weight: 156.27
definition:
  en: dl-Menthol contains not less than 98.
appearance:
  en: dl-Menthol occurs as colorless crystals. It has a characteristic and refreshing odor and a burning taste, fol-lowed by a cool taste. It is very soluble in ethanol (95) and in diethyl ether, and very slightly soluble in water. It sublimes gradually at room temperature.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Triturate dl-Menthol with an equal amount of camphor, chloral hydrate or thymol: the mixture liquefies. (2) Shake 1 g of dl-Menthol with 20 mL of sulfuric acid: the mixture becomes turbid with a yellow-red color. Allow to stand for 3 hours: a clear, oily layer possesses no aroma of menthol is separated. Congealing point <2.42> 27 – 289C D Optical rotation <2.49> [a]20: －2.0 – ＋2.09(2.5 g, ethanol (95), 25 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Non-volatile residue—Volatilize 2.0 g of dl-Menthol on a water bath, and dry the residue at 1059C for 2 hours: the residue weighs not more than 1.0 mg. Thymol—Add 0.20 g of dl-Menthol to a cold mixture of 2 mL of acetic acid (100), 6 drops of sulfuric acid and 2 drops of nitric acid: no green to blue-green color immedi-ately develops. Nitromethane or nitroethane—To 0.5 g of dl-Men-thol placed in a flask add 2 mL of a solution of sodium hy-droxide (1 in 2) and 1 mL of hydrogen peroxide (30), connect a reflux condenser to the flask, and boil the mixture gently for 10 minutes. After cooling, add water to make exactly 20 mL, and filter. Take 1 mL of the filtrate in a Nessler tube, add water to make 10 mL, neutralize with dilute hydrochlo-ric acid, then add 1 mL of dilute hydrochloric acid, and cool. To the mixture add 1 mL of a solution of sulfanilic acid (1 in 100), allow to stand for 2 minutes, and then add 1 mL of a solution of N,N-diethyl-N?-1-naphthylethylenedia-mine oxalate (1 in 1000) and water to make 25 mL: no red-purple color immediately develops.
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 2 g of dl-Menthol, add ex-actly 20 mL of a mixture of dehydrated pyridine and acetic anhydride (8:1), connect a reflux condenser, and heat on a water bath for 2 hours. Wash down the condenser with 20 mL of water, and titrate <2.50> with 1 mol/L sodium hy-droxide VS (indicator: 5 drops of phenolphthalein TS). Per-form a blank determination in the same manner. Each mL of 1 mol/L sodium hydroxide VS ＝ 156.3 mg of C10H20O
storage conditions:
  en: Containers—Tight containers. Storage—In a cold place.
type: PharmacopoeiaMonograph

dl-methylephedrine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: ‌dl-Methylephedrine Hydrochloride
  ja: dl-メチルエフェドリン塩酸塩
monograph id: JP18-dl-methylephedrine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C11H17NO.HCl
molecular weight: 215.72
cas number: 18760-80-0
appearance:
  en: dl-Methylephedrine Hydrochloride occurs as colorless crystals or a white crystalline powder. It is freely soluble in water, sparingly soluble in ethanol (99.5), slightly soluble in acetic acid (100), and practically insoluble in acetic anhydride. A solution of dl-Methylephedrine Hydrochloride (1 in 20) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of dl-Methylephedrine Hydrochloride (1 in 2000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of dl-Methylephedrine Hydrochloride, previously dried, as di-rected in the potassium chloride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensi-ties of absorption at the same wave numbers. A solution of dl-Methylephedrine Hydrochloride (1 in 10) responds to Qualitative Tests <1.09> for chloride. pH <2.54> The pH of a solution prepared by dissolving 1.0 g of dl-Methylephedrine Hydrochloride in 20 mL of water is between 4.5 and 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of dl-Methylephedrine Hydrochloride in 10 mL of water: the solution is clear and colorless. Heavy metals <1.07>—Proceed with 1.0 g of dl- Methylephedrine Hydrochloride according to Method 4, and perform the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 50 mg of dl-Methyl-ephedrine Hydrochloride in 20 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine each peak area by the automatic integration method: the total area of the peaks other than the peak of methylephedrine ob-tained from the sample solution is not larger than the peak area of methylephedrine from the standard solution. Operating conditions— Detector: An ultraviolet absorption photometer (wave- length: 257 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 409C. Mobile phase: Dissolve 13.6 g of potassium dihydrogen phosphate and 3 g of sodium 1-heptane sulfonate in 1000 mL of water, and adjust the pH to 2.5 with phosphoric acid. To 900 mL of this solution add 200 mL of acetonitrile. Flow rate: Adjust so that the retention time of methylephedrine is about 10 minutes. Time span of measurement: About 2 times as long as the retention time of methylephedrine, beginning after the sol-vent peak. System suitability— Test for required detectability: To exactly 2 mL of the standard solution add water to make exactly 20 mL. Con-firm that the peak area of methylephedrine obtained with 20 mL of this solution…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.4 g of dl-Methylephedrine Hydrochloride, previously dried, dissolve in 80 mL of a mix-ture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 21.57 mg of C11H17NO.HCl
storage conditions:
  en: Containers—Well-closed contain-ers.
type: PharmacopoeiaMonograph

dobutamine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Dobutamine Hydrochloride
  ja: ドブタミン塩酸塩
monograph id: JP18-dobutamine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C18H23NO3.HCl
molecular weight: 337.84
cas number: 49745-95-1
definition:
  en: Dobutamine Hydrochloride, when dried, contains not less than 98.
appearance:
  en: Dobutamine Hydrochloride occurs as white to very pale orange, crystalline powder or grains. It is freely soluble in methanol, sparingly soluble in water and in ethanol (95), and practically insoluble in diethyl ether. A solution of Dobutamine Hydrochloride (1 in 100) shows no optical rotation.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the infrared absorption spec- ‌878 tra of Dobutamine Hydrochloride, previously dried, as di-rected in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of dried Dobuta-mine Hydrochloride RS: both spectra exhibit similar intensi-ties of absorption at the same wave numbers. (2) A solution of Dobutamine Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> (2) for chloride. pH <2.54> Dissolve 1.0 g of Dobutamine Hydrochloride in 100 mL of water: the pH of this solution is between 4.0 and 5.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.5 g of Dobutamine Hydrochloride in 30 mL of water: the solu-tion is clear and colorless. Heavy metals <1.07>—Dissolve 1.0 g of Dobutamine Hydrochloride in 40 mL of water by warming, cool, and add 2 mL of dilute acetic acid and water to make 50 mL. Per-form the test using this solution as the test solution. Prepare the control solution as follows: to 2.0 mL of Standard Lead Solution add water to make 50 mL (not more than 20 ppm). Related substances—Dissolve 0.10 g of Dobutamine Hydrochloride in 10 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 200 mL, and use this solution as the standard solution. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solu-tion on a plate of silica gel for thin-layer chromatography. Develop the plate with a mixture of chloroform, methanol and formic acid (78:22:5) to a distance of about 12 cm, and air-dry the plate. Allow the plate to stand for 5 minutes in iodine vapor: the spots other than the principal spot ob-tained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.30z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.1 g each of Dobutamine Hydrochloride and Dobutamine Hydrochloride RS, each previously dried, dissolve separately in exactly 10 mL of the internal standard solution, add diluted methanol (1 in 2) to make 50 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with 5 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and calculate the ratios, QT and QS, of the peak area of dobutamine to that of the internal standard, respectively. Amount (mg) of dobutamine hydrochloride (C18H23NO3.HCl) ＝ MS × QT/QS MS: Amount (mg) of Dobutamine Hydrochloride RS taken Internal standard solution—A solution of salicylamide in diluted methanol (1 in 2) (1 in 125). Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 280 nm). Column: A stainless steel column 4.0 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (7 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of tartrate buffer solution (pH 3.0) and methanol (7:3). Flow rate: Adjust so that the retention time of dobuta-mine is about 7 minutes. System suitability— System performance: When the procedure is run with 5 mL of the standard solution under the above operating condi-tions, dobutamine and internal standard are eluted in this order with the resolution between these peaks being not less than 5. System repeatability: When the test is repeated 6 times with 5 mL of the standard solution under the above operating conditions, the relative standard deviation of the ratios of the peak area of dobutamine to that of the internal standard is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

docetaxel-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Docetaxel Hydrate
  ja: ドセタキセル水和物
monograph id: JP18-docetaxel-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C43H53NO14.3H2O
molecular weight: 861.93
definition:
  en: Docetaxel Hydrate contains not less than 97.
appearance:
  en: Docetaxel Hydrate occurs as a white crystalline powder. It is freely soluble in N,N-dimethylformamide and in ethanol (99.5), soluble in methanol and in dichloromethane, and practically insoluble in water. It decomposes on exposure to light.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Docetaxel Hydrate in methanol (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Docetaxel Hydrate RS pre-pared in the same manner as the sample solution: both spec-tra exhibit similar intensities of absorption at the same wave-lengths. (2) Dissolve 60 mg of Docetaxel Hydrate in 1 mL of dichloromethane. Perform the test with this solution as di-rected in the solution method under Infrared Spectropho-tometry <2.25> using a fixed cell composed of potassium bromide optical plates with the cell length of 0.1 mm, and compare the spectrum with the Reference Spectrum or the spectrum of Docetaxel Hydrate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. ‌JP XVIII Official Monographs / Docetaxel Injection 879 Optical rotation <2.49> [a]20: －39 – －419(0.2 g calculated Amount (mg) of docetaxel (C H NO ) ＝ M × A /A D 43 53 14 S T S on the anhydrous and residual solvent-free basis, methanol, 20 mL, 100 mm).
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Docetaxel Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Perform the test with 10 mL of the sample solution obtained in the Assay, as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area by the automatic in-tegration method, and calculate the amount of them by the area percentage method: the amount of each peak, having the relative retention time of about 0.97, about 1.08, and about 1.13 to docetaxel, is not more than 0.50z, not more than 0.30z, and not more than 0.30z, respectively, the amount of each peak other than docetaxel and the peaks MS: Amount (mg) of Docetaxel RS taken, calculated on the anhydrous and residual solvent-free basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 232 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (3.5 mm in particle diameter). Column temperature: A constant temperature of about 459C. Mobile phase A: Water. Mobile phase B: Acetonitrile for liquid chromatography. Flowing of mobile phase: Control the gradient by mixing the mobile phases A and B as directed in the following table. mentioned above is not more than 0.10z, and the total amount of the peaks other than docetaxel is not more than Time after injection of sample (min) Mobile phase A (volz) Mobile phase B (volz) 1.0z. For the area of the peak, having the relative retention time of about 0.97 to docetaxel, multiply the correction factor 1.6. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: For 39 minutes after injec-tion, beginning after the solvent peak. System suitability— Test for required…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 50 mg each of Docetaxel Hydrate and Docetaxel RS (separately determine the water <2.48> and the residual solvent in the same manner as Docetaxel Hydrate), dissolve them separately in 2.5 mL of ethanol (99.5), add a mixture of water, acetonitrile for liquid chromatography and acetic acid (100) (1000:1000:1) to make exactly 50 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of docetaxel in each solution. 0 – 9 72 28 9 – 39 72 → 28 28 → 72 Flow rate: 1.2 mL per minute. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of docetaxel are not less than 100,000 and not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of docetaxel is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers. Storage—Light-resistant.
type: PharmacopoeiaMonograph

domperidone
type: ChemicalDrugMonograph
pref label:
  en: Domperidone
  ja: ドンペリドン
monograph id: JP18-domperidone
publisher: JP
status: Official
version: 18
molecular formula: C22H24ClN5O2
molecular weight: 425.91
cas number: 57808-66-9
definition:
  en: Domperidone, when dried, contains not less than 99.
appearance:
  en: Domperidone occurs as a white to pale yellow, crystalline powder or powder. It is freely soluble in acetic acid (100), slightly soluble in methanol and in ethanol (99.5), very slightly soluble in 2-propanol, and practically insoluble in water. Melting point: about 2439C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Domperidone in a mixture of 2-propanol and 0.1 mol/L hydrochloric acid TS (9:1) (1 in 50,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Domperidone as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave ‌882 numbers.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Domperidone according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 30 mg of Domperidone in 100 mL of methanol, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add methanol to make exactly 200 mL, and use this solution as the stand-ard solution. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area of each solution by the automatic integration method: the area of each peak other than domperidone obtained from the sample solution is not larger than 1/2 times the peak area of domperidone from the standard solution. Furthermore, the total area of the peaks other than domperidone is not larger than the peak area of domperidone from the standard solution. ers. Storage—Light-resistant. Donepezil Hydrochloride
type: PharmacopoeiaMonograph

donepezil-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Donepezil Hydrochloride
  ja: ドネペジル塩酸塩
monograph id: JP18-donepezil-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C24H29NO3.HCl
molecular weight: 415.95
definition:
  en: Donepezil Hydrochloride contains not less than 98.
appearance:
  en: Donepezil Hydrochloride occurs as a white crystalline powder. It is soluble in water, and slightly soluble in ethanol (99.5). A solution of Donepezil Hydrochloride (1 in 100) shows no optical rotation. Donepezil Hydrochloride shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Donepezil Hydrochloride (1 in 50,000) as di-rected under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Donepezil Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Donepezil Hydrochloride as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Donepezil Hydrochloride RS: both spectra exhibit similar intensities of absorption at the same wave numbers. If any difference appears between the spectra, recrystallize the sample and the RS according to the method otherwise specified, filter and dry the crystals, and perform the test with the crystals. A solution of Donepezil Hydrochloride (1 in 50) responds to Qualitative Tests <1.09> (2) for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—To 1.0 g of Donepezil Hydrochloride in a porcelain or platinum crucible add 5 mL of sulfuric acid, incinerate by heating gradually, then incin-erate by ignition between 500 and 6009C. If a carbonized residue still retains, moisten the residue with a little amount of sulfuric acid, and incinerate again by ignition between 500 and 6009C. After cooling, dissolve the residue with 3 mL of hydrochloric acid, then evaporate to dryness on a water bath or hot plate, and dissolve the residue with 10 mL of water by warming. Then, proceed as directed in Method 4, and per-form the test. Prepare the control solution with 1.0 mL of Standard Lead Solution (not more than 10 ppm). (2) Related substances—Dissolve 50 mg of Donepezil Hydrochloride in 25 mL of the mobile phase. To 10 mL of this solution add the mobile phase to make 50 mL, and use this solution as the sample solution. Pipet 2 mL of the sam-ple solution, and add the mobile phase to make exactly 100 ‌JP XVIII Official Monographs / Donepezil Hydrochloride Fine Granules 883 mL. Pipet 5 mL of this solution, add the mobile phase to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liq-uid Chromatography <2.01> according to the following con-ditions, and determine each peak area by the automatic in-tegration method: the area of the peak other than donepezil obtained from the sample solution is not larger than the peak area of donepezil from the standard solution. Operating conditions— Detector, column, column temperature, mobile phase, and flow rate: Proceed as directed in the operating conditions in the Assay. Time span of measurement: About 2 times as long as the retention time of donepezil, beginning after the solvent peak. System suitability— System performance: When the procedure is run with 20 mL of the standard solution under the above operating con-ditions, the number of theor…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.5 g of Domperidone, pre-viously dried, dissolve in 50 mL of acetic acid (100), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentio-metric titration). Perform a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 42.59 mg of C22H24ClN5O2
storage conditions:
  en: Containers—Well-closed contain-
type: PharmacopoeiaMonograph

dopamine-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Dopamine Hydrochloride
  ja: ドパミン塩酸塩
monograph id: JP18-dopamine-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C8H11NO2.HCl
molecular weight: 189.64
appearance:
  en: Dopamine Hydrochloride occurs as white, crystals or crystalline powder. It is freely soluble in water and in formic acid, and spar-ingly soluble in ethanol (95). Melting point: about 2489C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Dopamine Hydrochloride in 0.1 mol/L hydro-chloric acid TS (1 in 25,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar in-tensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dopamine Hydrochloride as directed in the potassium chlo-ride disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Dopamine Hydrochloride (1 in 50) re-sponds to Qualitative Tests <1.09> (1) for chloride. pH <2.54> Dissolve 1.0 g of Dopamine Hydrochloride in 50 mL of water: the pH of this solution is between 4.0 and 5.5.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Dopamine Hydrochloride in 10 mL of water: the solution is clear and colorless. Sulfate <1.14>—Perform the test with 0.8 g of Dopa- mine Hydrochloride. Prepare the control solution with 0.35 mL of 0.005 mol/L sulfuric acid VS (not more than 0.021z). Heavy metals <1.07>—Proceed with 1.0 g of Dopa- mine Hydrochloride according to Method 1, and perform the test. Prepare the control solution with 2.0 mL of Stand-ard Lead Solution (not more than 20 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Dopamine Hydrochloride according to Method 1, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.1 g of Dopamine Hydrochloride in 10 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 250 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of cellulose with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of 1-propanol, water and acetic acid (100) (16:8:1) to a distance of about 10 cm, and air-dry the plate. Spray evenly a solu-tion of ninhydrin in acetone (1 in 50) on the plate, and heat the plate at 909C for 10 minutes: the spots other than the principal spot obtained from the sample solution are not more intense than the spot from the standard solution. Loss on drying <2.41> Not more than 0.5z (1 g, 1059C, 3 hours). Residue on ignition <2.44> Not more than 0.1z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.2 g of Dopamine Hydro-chloride, previously dried, dissolve in 5 mL of formic acid, add exactly 15 mL of 0.1 mol/L perchloric acid VS, and heat on a water bath for 15 minutes. After cooling, add 50 mL of acetic acid (100), and titrate <2.50> the excess perchloric acid with 0.1 mol/L sodium acetate VS (potentiometric titration). Perform a blank determination in the same manner. Each mL of 0.1 mol/L perchloric acid VS ＝ 18.96 mg of C8H11NO2.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

doripenem-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Doripenem Hydrate
  ja: ドリペネム水和物
monograph id: JP18-doripenem-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C15H24N4O6S2.H2O
molecular weight: 438.52
definition:
  en: Doripenem Hydrate contains not less than 970 mg (potency) and not more than 1020 mg (potency) per mg, calculated on the anhydrous basis.
appearance:
  en: Doripenem Hydrate occurs as a white to pale yellow-brown-white crystalline powder. It is sparingly soluble in water, slightly soluble in metha-nol, and practically insoluble in ethanol (99.5). It is gradually colored to pale yellow-brown-white by light. Identiˆcation (1) Determine the absorption spectrum of a Doripenem Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Doripenem RS: both spectra exhibit similar in-tensities of absorption at the same wave numbers. D Optical rotation <2.49> [a]20: ＋33 – ＋389(0.25 g calcu-lated on the anhydrous basis, water, 25 mL, 100 mm). pH <2.54> Dissolve 0.3 g of Doripenem Hydrate in 30 mL of water: the pH of the solution is between 4.5 and 6.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 0.2 g of Doripenem Hydrate in 20 mL of water, and perform the test with this solution as directed under Turbidity Meas-urement <2.61>: the solution is clear. Perform the test with this solution according to Method 2 under Methods for Color Matching <2.65>: the solution is not more colored than Matching Fluid Y4. Heavy metals <1.07>—Moisten 1.0 g of Doripenem Hydrate with sulfuric acid, cover loosely, and heat gently to carbonize. Then proceed according to Method 2, and per-form the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). Related substances (i)—Dissolve 20 mg of Doripen-em Hydrate in 10 mL of water, and use this solution as the sample solution. Pipet 1 mL of the sample solution, add water to make exactly 100 mL, and use this solution as the standard solution. Perform the test with exactly 20 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions. Determine each peak area by the auto-matic integration method: the peak areas of related sub-stance A, having the relative retention time of about 2.2 to doripenem, related substance B, having the relative retention time of about 2.5, and related substance C, having the rela-tive retention time of about 3.2, obtained from the sample solution, are not larger than 1/10 times the peak area of doripenem from the standard solution, and the area of the peak other than doripenem, the peaks mentioned above and the peak having the relative retention time of about 2.1, from the sample solution, is not larger than 1/20 times the peak area of doripenem from the standard solution. Further-more, the total area of the peaks other than doripenem and the peak having the relative retention time of about 2.1 from the sample solution is not larger than 1/2 times the peak area of doripenem from the standard solution. Operating conditions— Detector: An ultraviolet a…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately amounts of Doripenem Hydrate and Doripenem RS (separately determine the water <2.48> in the same manner as Doripenem Hydrate), equivalent to about 25 mg (potency), dissolve each in water to make ex-actly 200 mL, and use these solutions as the sample solution and the standard solution, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of doripenem in each solution. Amount [mg (potency)] of doripenem (C15H24N4O6S2) ＝ MS × AT/AS × 1000 MS: Amount [mg (potency)] of Doripenem RS taken, cal-culated on the anhydrous basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 300 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (5 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Adjust the pH of 90 mL of 0.02 mol/L potassium dihydrogen phosphate TS to pH 5.6 – 5.7 with a solution prepared by dissolving 3.48 g of dipotassium hydro-gen phosphate in water to make 1000 mL. To 100 mL of this solution add water to make exactly 1000 mL. To 970 mL of this solution add 30 mL of acetonitrile. Flow rate: Adjust so that the retention time of doripenem is about 15 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of doripenem are not less than 5000 and not more than 1.3, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of doripenem is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers. Storage—At a temperature between 29C and 89C.
type: PharmacopoeiaMonograph

dorzolamide-hydrochloride
type: ChemicalDrugMonograph
pref label:
  en: Dorzolamide Hydrochloride
  ja: ドルゾラミド塩酸塩
monograph id: JP18-dorzolamide-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C10H16N2O4S3.HCl
molecular weight: 360.9
cas number: 130693-82-2
appearance:
  en: Dorzolamide Hydrochloride occurs as a white crystalline powder. It is soluble in water, sparingly soluble in methanol, and very slightly soluble in ethanol (99.5). It dissolves in diluted ammonia solution (28) (13 in 400). Time span of measurement: About 3 times as long as the retention time of dorzolamide, beginning after the solvent peak. System suitability— Test for required detectability: Pipet 2 mL of the sample solution, and add a mixture of water and methanol (4:1) to make exactly 100 mL. Pipet 1 mL of this solution, add a mixture of water and methanol (4:1) to make exactly 20 mL, and use this solution as the solution for system suitability test. Confirm that the peak area of dorzolamide obtained with 10 mL of the solution for system suitability test is equivalent to 0.07 to 0.13z of that with 10 mL of the sample solution. System performance: To 1 mL of the sample solution add 2 mL of a mixture of water and methanol (4:1). When the procedure is run with 10 mL of this solution under the above 404.7 Optical rotation [a]25 : －16.0 – －17.59(0.25 g calcu- operating conditions, the number of theoretical plates and lated on the anhydrous basis, water, 25 mL, 100 mm). Dorzolamide Hydrochloride shows crystal polymorphism.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Dorzolamide Hydrochloride in a solution of hy-drochloric acid in methanol (9 in 1000) (3 in 200,000) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum or the spectrum of a solution of Dorzolamide Hydrochloride RS prepared in the same manner as the sample solution: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dor-zolamide Hydrochloride as directed in the potassium bro-mide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spectrum or the spectrum of Dorzolamide Hydrochloride RS: both spec-tra exhibit similar intensities of absorption at the same wave numbers. A solution of Dorzolamide Hydrochloride (1 in 100) responds to Qualitative Tests <1.09> for chloride.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 2.0 g of Dorzolamide Hydrochloride according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Related substances—Dissolve 30 mg of Dorzolamide Hydrochloride in 50 mL of a mixture of water and methanol (4:1), and use this solution as the sample solution. Perform the test with 10 mL of the sample solution as directed under Liquid Chromatography <2.01> according to the following conditions. Determine each peak area by the automatic in-tegration method, and calculate their amounts by the area percentage method: the amount of the peaks other than dor-zolamide is not more than 0.1z. Operating conditions— Detector, column, column temperature, and flow rate: Proceed as directed in the operating conditions in the Assay. Mobile phase A: Adjust to pH 4.5 of a mixture of water and acetic acid (100) (1000:1) with triethylamine. the symmetry factor of the peak of dorzolamide are not less than 4000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the solution for system suitability test under the above operating conditions, the relative standard devia-tion of the peak area of dorzolamide is not more than 7z. Enantiomer—Dissolve 20 mg of Dorzolamide Hydro-chloride in 4 mL of diluted ammonia solution (28) (13 in 400), and extract this solution with two 4-mL portions of ethyl acetate. Combine the extracts, and evaporate the ethyl acetate at 509C under a current of nitrogen. Dissolve the residue in 3 mL of acetonitrile, add 3 drops of (S)-1-phenylethyl isocyanate, and allow to stand at 509C for 10 minutes. Evaporate at 509C under a current of nitrogen, dis-solve the residue in 10 mL of a mixture of tert-butylmethyl ether, acetic acid (100) and acetonitrile (873:100:27), and use this solution as the sample solution. Perform the test with 5 mL of the sample solution as directed under Liquid Chroma-tography <2.01> acco…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 20 mg each of Dorzolamide Hydrochloride and Dorzolamide Hydrochloride RS (separately, determine the water <2.48> in the same manner as Dorzolamide Hydrochloride), dissolve in a mixture of water and methanol (4:1) to make exactly 100 mL, and use these solutions as the sample solution and the standard solu-tion, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the fol-lowing conditions, and determine the peak areas, AT and AS, of dorzolamide in each solution. Amount (mg) of dorzolamide hydrochloride (C10H16N2O4S3.HCl) ＝ MS × AT/AS MS: Amount (mg) of Dorzolamide Hydrochloride RS taken, calculated on the anhydrous basis Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 254 nm). Column: A stainless steel column 4.6 mm in inside diame-ter and 8.3 cm in length, packed with octylsilanized silica gel for liquid chromatography (3 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: Adjust to pH 4.5 of a mixture of water and acetic acid (100) (1000:1) with triethylamine. Flow rate: Adjust so that the retention time of dorzola-mide is about 9 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of dorzolamide are not less than 4000 and not more than 1.5, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of dorzolamide is not more than 1.0z.
storage conditions:
  en: Containers—Well-closed contain-ers.

doxapram-hydrochloride-hydrate
type: ChemicalDrugMonograph
pref label:
  en: Doxapram Hydrochloride Hydrate
  ja: ドキサプラム塩酸塩水和物
monograph id: JP18-doxapram-hydrochloride-hydrate
publisher: JP
status: Official
version: 18
molecular formula: C24H30N2O2.HCl.H2O
molecular weight: 432.98
appearance:
  en: Doxapram Hydrochloride Hydrate occurs as white, crystals or crystalline powder. It is freely soluble in methanol and in acetic acid (100), sparingly soluble in water, in ethanol (95) and in acetic anhy-dride, and practically insoluble in diethyl ether.
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Doxapram Hydrochloride Hydrate (1 in 2500) as directed under Ultraviolet-visible Spectrophotometry <2.24>, and compare the spectrum with the Reference Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dox-apram Hydrochloride Hydrate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. A solution of Doxapram Hydrochloride Hydrate (1 in 50) responds to Qualitative Tests <1.09> for chloride. pH <2.54> Dissolve 1.0 g of Doxapram Hydrochloride Hy-drate in 50 mL of water: the pH of this solution is between 3.5 and 5.0.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Clarity and color of solution—Dissolve 1.0 g of Doxapram Hydrochloride Hydrate in 50 mL of water: the solution is clear and colorless. Sulfate <1.14>—Perform the test with 1.0 g of Dox- apram Hydrochloride Hydrate. Prepare the control solution with 0.50 mL of 0.005 mol/L sulfuric acid VS (not more than 0.024z). Heavy metals <1.07>—Proceed with 2.0 g of Dox- apram Hydrochloride Hydrate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 10 ppm). Arsenic <1.11>—Prepare the test solution with 1.0 g of Doxapram Hydrochloride Hydrate according to Method 3, and perform the test (not more than 2 ppm). Related substances—Dissolve 0.5 g of Doxapram Hy-drochloride Hydrate in 10 mL of methanol, and use this so-lution as the sample solution. Pipet 3 mL of the sample solu-tion, and add methanol to make exactly 100 mL. Pipet 5 mL of this solution, add methanol to make exactly 50 mL, and use this solution as the standard solution. Perform the test ‌896 with these solutions as directed under Thin-layer Chroma-tography <2.03>. Spot 6 mL each of the sample solution and standard solution on a plate of silica gel for thin-layer chro-matography. Develop the plate with a mixture of chlo-roform, formic acid, ethyl formate and methanol (8:3:3:2) to a distance of about 10 cm, and air-dry the plate. Allow the plate to stand in iodine vapor: the spots other than the prin-cipal spot obtained from the sample solution are not more intense than the spot from the standard solution. Water <2.48> 3.5 – 4.5z (0.5 g, volumetric titration, direct titration). Residue on ignition <2.44> Not more than 0.3z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.8 g of Doxapram Hydro-chloride Hydrate, dissolve in 50 mL of a mixture of acetic anhydride and acetic acid (100) (7:3), and titrate <2.50> with 0.1 mol/L perchloric acid VS (potentiometric titration). Per-form a blank determination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L perchloric acid VS ＝ 41.50 mg of C24H30N2O2.HCl
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

doxazosin-mesilate
type: ChemicalDrugMonograph
pref label:
  en: Doxazosin Mesilate
  ja: ドキサゾシンメシル酸塩
monograph id: JP18-doxazosin-mesilate
publisher: JP
status: Official
version: 18
molecular formula: C23H25N5O5.CH4O3S
molecular weight: 547.58
cas number: 77883-43-3
definition:
  en: Doxazosin Mesilate, when dried, contains not less than 98.
appearance:
  en: Doxazosin Mesilate occurs as a white to yel-lowish white crystalline powder. It is freely soluble in dimethylsulfoxide, slightly soluble in water and in methanol, and very slightly soluble in ethanol (99.5). A solution of Doxazosin Mesilate in dimethylsulfoxide solution (1 in 20) shows no optical rotation. Melting point: about 2729C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Doxazosin Mesilate in 0.01 mol/L hydrochloric acid-methanol TS (1 in 200,000) as directed under Ultravio-let-visible Spectrophotometry <2.24>, and compare the spec-trum with the Reference Spectrum or the spectrum of a solu-tion of Doxazosin Mesilate RS prepared in the same manner as the sample solution: both spectra exhibit similar intensi-ties of absorption at the same wavelengths. Determine the infrared absorption spectrum of Dox-azosin Mesilate as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and com-pare the spectrum with the Reference Spectrum or the spec- trum of Doxazosin Mesilate RS: both spectra exhibit similar intensities of absorption at the same wave numbers. 30 mg of Doxazosin Mesilate responds to Qualitative Tests <1.09> (2) for mesilate.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Heavy metals <1.07>—Proceed with 1.0 g of Doxazosin Mesilate according to Method 2, and perform the test. Prepare the control solution with 2.0 mL of Standard Lead Solution (not more than 20 ppm). (2) Related substances—Dissolve 20 mg of Doxazosin Mesilate in 5 mL of a mixture of methanol and acetic acid (100) (1:1), and use this solution as the sample solution. Pipet 1 mL of the sample solution, add a mixture of metha-nol and acetic acid (100) (1:1) to make exactly 100 mL. Pipet 5 mL of this solution, add a mixture of methanol and acetic acid (100) (1:1) to make exactly 10 mL, and use this solution as the standard solution. Perform the test with these solu-tions as directed under Thin-layer Chromatography <2.03>. Spot 5 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with an upper layer of a mixture, prepared by adding 1 volume of water and 1 volume of acetic acid (100) to 2 volumes of 4-methyl-2-pen-tanon and shaking, to a distance of about 10 cm, and air-dry the plate. Examine under ultraviolet light (main wavelength: 254 nm): the spot at the Rf value about 0.15 obtained from the sample solution is not more intense than the spot from the standard solution, and no spots other than the principal spot and other than the spots mentioned above appear from the sample solution. Loss on drying <2.41> Not more than 1.0z (1 g, 1059C, 4 hours). Residue on ignition <2.44> Not more than 0.2z (1 g).
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 25 mg each of Doxazosin Mesilate and Doxazosin Mesilate RS, previously dried, dis-solve separately in methanol to make exactly 50 mL. Pipet 3 mL each of these solutions, add the mobile phase to make exactly 100 mL, and use these solutions as the sample solu-tion and the standard solution, respectively. Perform the test with exactly 10 mL each of the sample solution and standard solution as directed under Liquid Chromatography <2.01> according to the following conditions, and determine the peak areas, AT and AS, of doxazosin in each solution. Amount (mg) of doxazosin mesilate (C23H25N5O5.CH4O3S) ＝ MS × AT/AS MS: Amount (mg) of Doxazosin Mesilate RS taken Operating conditions— Detector: An ultraviolet absorption photometer (wave-length: 246 nm). Column: A stainless steel column 3.9 mm in inside diame-ter and 15 cm in length, packed with octadecylsilanized silica gel for liquid chromatography (4 mm in particle diameter). Column temperature: A constant temperature of about 259C. Mobile phase: A mixture of 0.05 mol/L potassium dihy-drogen phosphate TS (pH 3.0), methanol and acetonitrile (12:8:3). Flow rate: Adjust so that the retention time of doxazosin is about 5 minutes. System suitability— System performance: When the procedure is run with 10 mL of the standard solution under the above operating con-ditions, the number of theoretical plates and the symmetry factor of the peak of doxazosin are not less than 2000 and ‌JP XVIII Official Monographs / Doxazosin Mesilate Tablets 897 not more than 2.0, respectively. System repeatability: When the test is repeated 6 times with 10 mL of the standard solution under the above operat-ing conditions, the relative standard deviation of the peak area of doxazosin is not more than 1.0z.
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

doxifluridine
type: ChemicalDrugMonograph
pref label:
  en: Doxifluridine
  ja: ドキシフルリジン
monograph id: JP18-doxifluridine
publisher: JP
status: Official
version: 18
definition:
  en: Doxifluridine, when dried, contains not less than 98.
appearance:
  en: Doxifluridine occurs as a white crystalline powder. It is freely soluble in N,N-dimethylformamide, soluble in water and in methanol, and slightly soluble in ethanol (99.5). It dissolves in 0.1 mol/L hydrochloric acid TS and in 0.01 mol/L sodium hydroxide TS. Melting point: about 1919C (with decomposition).
test specification: IdentificationSpecification
  test name:
    en: Identification
  test type: TestType-Identification
  test conditions:
    en: (1) Determine the absorption spectrum of a solution of Doxifluridine in 0.1 mol/L hydrochloric acid TS (1 in 50,000) as directed under Ultraviolet-visible Spectro-photometry <2.24>, and compare the spectrum with the Ref-erence Spectrum: both spectra exhibit similar intensities of absorption at the same wavelengths. (2) Determine the infrared absorption spectrum of Doxifluridine, previously dried, as directed in the potassium bromide disk method under Infrared Spectrophotometry <2.25>, and compare the spectrum with the Reference Spec- trum: both spectra exhibit similar intensities of absorption at the same wave numbers. Optical rotation <2.49> [a]20 : ＋160 – ＋1749(after drying, 0.1 g, water, 10 mL, 100 mm). pH <2.54> The pH of a solution obtained by dissolving 0.10 g of Doxifluridine in 10 mL of water is between 4.2 and 5.2.
test specification: PuritySpecification
  test name:
    en: Purity
  test type: TestType-Purity
  test conditions:
    en: (1) Fluoride—Dissolve 0.10 g of Doxifluridine in 10.0 mL of diluted 0.01 mol/L sodium hydroxide TS (1 in 20). Transfer 5.0 mL of this solution into a 20-mL volumet-ric flask, add 5 mL of a mixture of acetone and lanthanum-alizarin complexone TS (2:1) and water to make 20 mL, allow to stand for 1 hour, and use this solution as the sample solution. Separately, put 1.0 mL of Standard Fluorine Solu-tion in a 20-mL volumetric flask, add 5.0 mL of diluted 0.01 mol/L sodium hydroxide TS (1 in 20) and 5 mL of the mix-ture of acetone and alizarin complexone TS (2:1), then proceed in the same manner as for preparation of the sample solution, and use the solution so obtained as the standard solution. Determine the absorbances, AT and AS, of the sam-ple solution and standard solution at 620 nm as directed under Ultraviolet-visible Spectrophotometory <2.24>, using a solution obtained in the same way with 5.0 mL of diluted 0.01 mol/L sodium hydroxide TS (1 in 20) as a blank: AT is not larger than AS. Chloride <1.03>—Perform the test with 0.30 g of Doxifluridine. Prepare the control solution with 0.30 mL of 0.01 mol/L hydrochloric acid VS (not more than 0.035z). Heavy metals <1.07>—Proceed with 1.0 g of Doxi-fluridine according to Method 1, and perform the test. Pre-pare the control solution with 2.0 mL of Standard Lead So-lution (not more than 20 ppm). Related substances—Dissolve 20 mg of Doxifluridine in 2 mL of methanol, and use this solution as the sample so-lution. Pipet 1 mL of the sample solution, and add methanol to make exactly 25 mL. Pipet 5 mL of this solution, add methanol to make exactly 50 mL, and use this solution as the standard solution. Perform the test with these solutions as directed under Thin-layer Chromatography <2.03>. Spot 10 mL each of the sample solution and standard solution on a plate of silica gel with fluorescent indicator for thin-layer chromatography. Develop the plate with a mixture of ethyl acetate, acetic acid (100) and water (17:2:1) to a dista…
test specification: AssaySpecification
  test name:
    en: Assay
  test type: TestType-Assay
  test conditions:
    en: Weigh accurately about 0.25 g of Doxifluridine, pre-viously dried, dissolve in 50 mL of N,N-dimethylformamide, and titrate <2.50> with 0.1 mol/L tetramethylammonium hy-droxide VS (potentiometric titration). Perform a blank de-termination in the same manner, and make any necessary correction. Each mL of 0.1 mol/L tetramethylammonium hydroxide VS ＝ 24.62 mg of C9H11FN2O5
storage conditions:
  en: Containers—Tight containers.
type: PharmacopoeiaMonograph

doxorubicin-hydrochloride
type: ChemicalDrugMonograph
monograph id: JP18-doxorubicin-hydrochloride
publisher: JP
status: Official
version: 18
molecular formula: C27H29NO11.HCl
molecular weight: 579.98
cas number: 25316-40-9
type: PharmacopoeiaMonograph