{"id":9352,"date":"2025-10-06T10:21:53","date_gmt":"2025-10-06T03:21:53","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=9352"},"modified":"2025-10-06T10:21:53","modified_gmt":"2025-10-06T03:21:53","slug":"diazepam","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/diazepam\/","title":{"rendered":"Diazepam"},"content":{"rendered":"

(Ph. Eur. monograph 0022)<\/p>\n

C16<\/sub>H13<\/sub>ClN2<\/sub>O\u00a0 \u00a0 284.7\u00a0 \u00a0 439-14-5<\/p>\n

Action and use<\/strong><\/p>\n

Benzodiazepine.<\/p>\n

Preparations<\/strong><\/p>\n

Diazepam Injection<\/p>\n

Diazepam Oral Solution<\/p>\n

Diazepam Rectal Solution<\/p>\n

Diazepam Tablets<\/p>\n

DEFINITION<\/h2>\n

7-Chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one.<\/p>\n

Content<\/h3>\n

99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or almost white, crystalline powder.<\/p>\n

Solubility<\/h3>\n

Very slightly soluble in water, soluble in ethanol (96 per cent).<\/p>\n

IDENTIFICATION<\/h2>\n

Infrared absorption spectrophotometry (2.2.24).<\/p>\n

Comparison: diazepam CRS.<\/p>\n

TESTS<\/h2>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29). Prepare the solutions protected from bright light.<\/p>\n

Test solution Dissolve 25.0 mg of the substance to be examined in 0.5 mL of acetonitrile R and dilute to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 10.0 mL with the mobile phase.<\/p>\n

Reference solution (b): Dissolve the contents of a vial of diazepam for system suitability CRS (containing impurities A, B and E) in 1.0 mL of the mobile phase.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: spherical end-capped octylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n

\u2014 temperature: 30 \u00b0C.<\/p>\n

Mobile phase: Mix 22 volumes of acetonitrile R, 34 volumes of methanol R and 44 volumes of a 3.4 g\/L solution of
\npotassium dihydrogen phosphate R previously adjusted to pH 5.0 with dilute sodium hydroxide solution R.<\/p>\n

Flow rate 1.0 mL\/min.<\/p>\n

Detection: Spectrophotometer at 254 nm.<\/p>\n

Injection 20 \u03bcL.<\/p>\n

Run time: About 4 times the retention time of diazepam.<\/p>\n

Identification of impurities: Use the chromatogram supplied with diazepam for system suitability CRS and the
\nchromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B and E.<\/p>\n

Relative retention: With reference to diazepam (retention time = about 9 min): impurity E = about 0.7; impurity A = about 0.8; impurity B = about 1.3.<\/p>\n

System suitability Reference solution (b):<\/p>\n

\u2014 resolution: minimum 2.5 between the peaks due to impurities E and A and minimum 6.0 between the peaks due to impurity A and diazepam.<\/p>\n

Limits:<\/p>\n

\u2014 correction factors: for the calculation of content, multiply the peak areas of the following impurities by the
\ncorresponding correction factor: impurity B = 1.3; impurity E = 1.3;<\/p>\n

\u2014 impurities A, B, E: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent);<\/p>\n

\u2014 unspecified impurities: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n

\u2014 total: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a)
\n(0.2 per cent);<\/p>\n

\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a)
\n(0.05 per cent).<\/p>\n

Loss on drying (2.2.32)<\/h4>\n

Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo at 60 \u00b0C for 4 h.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n

Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Dissolve 0.200 g in 50 mL of acetic anhydride R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).<\/p>\n

1 mL of 0.1 M perchloric acid is equivalent to 28.47 mg of C16<\/sub>H13<\/sub>ClN2<\/sub>O.<\/p>\n

STORAGE<\/h3>\n

Protected from light.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, E.<\/p>\n

Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) C, D, F.<\/p>\n

\"Diazepam-1\"<\/p>\n

A. 7-chloro-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one (nordazepam),<\/p>\n

\"Diazepam-2\"<\/p>\n

B. N-(2-benzoyl-4-chlorophenyl)-2-chloro-N-methylacetamide,<\/p>\n

\"Diazepam-3\"<\/p>\n

C. 3-amino-6-chloro-1-methyl-4-phenylquinolin-2(1H)-one,<\/p>\n

\"Diazepam-4\"<\/p>\n

D. [5-chloro-2-(methylamino)phenyl]phenylmethanone,<\/p>\n

\"Diazepam-5\"<\/p>\n

E. 6-chloro-1-methyl-4-phenylquinazolin-2(1H)-one,<\/p>\n

\"Diazepam-6\"<\/p>\n

F. 7-chloro-2-methoxy-5-phenyl-3H-1,4-benzodiazepine.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 0022) C16H13ClN2O\u00a0 \u00a0 284.7\u00a0 \u00a0 439-14-5 Action and use Benzodiazepine. Preparations Diazepam Injection Diazepam Oral Solution Diazepam Rectal Solution Diazepam Tablets DEFINITION 7-Chloro-1-methyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility Very slightly soluble in water, soluble in ethanol (96 per…<\/p>\n","protected":false},"author":3,"featured_media":9361,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-9352","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicinal-substances"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/9352","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=9352"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/9352\/revisions"}],"predecessor-version":[{"id":9363,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/9352\/revisions\/9363"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/9361"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=9352"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=9352"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=9352"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}