{"id":25538,"date":"2025-11-04T15:40:11","date_gmt":"2025-11-04T08:40:11","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=25538"},"modified":"2025-11-04T15:52:39","modified_gmt":"2025-11-04T08:52:39","slug":"nitrazepam","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/nitrazepam\/","title":{"rendered":"Nitrazepam"},"content":{"rendered":"

(Ph. Eur. monograph 0415)<\/p>\n

C_{15<\/sub>H_{11<\/sub>N_{3<\/sub>O_{3\u00a0<\/sub> \u00a0 \u00a0 \u00a0281.3\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 146-22-5<\/p>\n}}}}

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

Benzodiazepine.<\/p>\n

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

Nitrazepam Oral Suspension<\/p>\n

Nitrazepam Tablets<\/p>\n

DEFINITION<\/h2>\n
7-Nitro-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 yellow, crystalline powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, slightly soluble in ethanol (96 per cent).<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: nitrazepam CRS.<\/p>\n
TESTS<\/h2>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Carry out the test protected from light.<\/p>\n
Test solution: Dissolve 50 mg of the substance to be examined in acetonitrile R and dilute to 20.0 mL with the same solvent.<\/p>\n
Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with acetonitrile R. Dilute 1.0 mL of this solution to 10.0 mL with acetonitrile R.<\/p>\n
Reference solution (b): Dissolve 2 mg of clonazepam CRS in acetonitrile R and dilute to 100.0 mL with the same solvent. Dilute 1.0 mL of this solution to 10.0 mL with the test solution.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.25 m, \u00d8 = 4.0 mm;<\/p>\n
\u2014 stationary phase: octylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: 7.8 g\/L solution of sodium dihydrogen phosphate R adjusted to pH 3.0 with phosphoric acid R;<\/p>\n
\u2014 mobile phase B: acetonitrile R;<\/p>\n\n\n\n\n\n\n
Time<\/strong>
\n(min)<\/strong><\/td>\n Mobile phase A<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n Mobile phase B<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 3<\/td>\n 65<\/td>\n 35<\/td>\n<\/tr>\n
3 – 10<\/td>\n 65 \u2192 50<\/td>\n 35 \u2192 50<\/td>\n<\/tr>\n
10 – 20<\/td>\n 50<\/td>\n 50<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1 mL\/min.<\/p>\n
Detection: Spectrophotometer at 270 nm.<\/p>\n
Injection: 10 \u03bcL.<\/p>\n
Relative retention: With reference to nitrazepam (retention time = about 9 min): clonazepam = about 1.1.<\/p>\n
System suitability: Reference solution (b):<\/p>\n
\u2014 peak-to-valley ratio: minimum 4.0, where Hp = height above the baseline of the peak due to clonazepam and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to nitrazepam.<\/p>\n
Limits:<\/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) (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) (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 an oven at 105 \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 0.250 g in 25 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 28.13 mg of C_{15<\/sub>H_{11<\/sub>N_{3<\/sub>O_{3<\/sub>.<\/p>\n}}}}
STORAGE<\/h2>\n
Protected from light.<\/p>\n
IMPURITIES<\/h2>\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) A, B, C, D.<\/p>\n
$\"Nitrazepam\"$ <\/p>\n
A. 3-amino-6-nitro-4-phenylquinolin-2(1H)-one,<\/p>\n
$\"Nitrazepam\"$ <\/p>\n
B. (2-amino-5-nitrophenyl)phenylmethanone,<\/p>\n
$\"Nitrazepam\"$ <\/p>\n
C. 2-bromo-N-[4-nitro-2-(phenylcarbonyl)phenyl]acetamide,<\/p>\n
$\"Nitrazepam\"$ <\/p>\n
D. 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-[4-nitro-2-(phenylcarbonyl)phenyl]acetamide.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 0415) C15H11N3O3\u00a0 \u00a0 \u00a0 \u00a0281.3\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 146-22-5 Action and use Benzodiazepine. Preparations Nitrazepam Oral Suspension Nitrazepam Tablets DEFINITION 7-Nitro-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 yellow, crystalline powder. Solubility Practically insoluble in water, slightly soluble in ethanol (96 per cent). IDENTIFICATION…<\/p>\n","protected":false},"author":2,"featured_media":25578,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25538","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\/25538","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=25538"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25538\/revisions"}],"predecessor-version":[{"id":25603,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25538\/revisions\/25603"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25578"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25538"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25538"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25538"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time<\/strong> \n(min)<\/strong><\/td>\n	Mobile phase A<\/strong> \n(per cent V\/V)<\/strong><\/td>\n	Mobile phase B<\/strong> \n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 3<\/td>\n	65<\/td>\n	35<\/td>\n<\/tr>\n
3 – 10<\/td>\n	65 \u2192 50<\/td>\n	35 \u2192 50<\/td>\n<\/tr>\n
10 – 20<\/td>\n	50<\/td>\n	50<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 1 mL\/min.<\/p>\n Detection: Spectrophotometer at 270 nm.<\/p>\n Injection: 10 \u03bcL.<\/p>\n Relative retention: With reference to nitrazepam (retention time = about 9 min): clonazepam = about 1.1.<\/p>\n System suitability: Reference solution (b):<\/p>\n \u2014 peak-to-valley ratio: minimum 4.0, where Hp = height above the baseline of the peak due to clonazepam and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to nitrazepam.<\/p>\n Limits:<\/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) (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) (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 an oven at 105 \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 0.250 g in 25 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 28.13 mg of C_{15<\/sub>H_{11<\/sub>N_{3<\/sub>O_{3<\/sub>.<\/p>\n}}}} STORAGE<\/h2>\n Protected from light.<\/p>\n IMPURITIES<\/h2>\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) A, B, C, D.<\/p>\n $\"Nitrazepam\"$ <\/p>\n A. 3-amino-6-nitro-4-phenylquinolin-2(1H)-one,<\/p>\n $\"Nitrazepam\"$ <\/p>\n B. (2-amino-5-nitrophenyl)phenylmethanone,<\/p>\n $\"Nitrazepam\"$ <\/p>\n C. 2-bromo-N-[4-nitro-2-(phenylcarbonyl)phenyl]acetamide,<\/p>\n $\"Nitrazepam\"$ <\/p>\n D. 2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N-[4-nitro-2-(phenylcarbonyl)phenyl]acetamide.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 0415) C15H11N3O3\u00a0 \u00a0 \u00a0 \u00a0281.3\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 146-22-5 Action and use Benzodiazepine. Preparations Nitrazepam Oral Suspension Nitrazepam Tablets DEFINITION 7-Nitro-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 yellow, crystalline powder. Solubility Practically insoluble in water, slightly soluble in ethanol (96 per cent). IDENTIFICATION…<\/p>\n","protected":false},"author":2,"featured_media":25578,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25538","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\/25538","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=25538"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25538\/revisions"}],"predecessor-version":[{"id":25603,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25538\/revisions\/25603"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25578"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25538"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25538"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25538"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or yellow, crystalline powder.<\/p>\n

Solubility<\/h3>\nPractically insoluble in water, slightly soluble in ethanol (96 per cent).<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison: nitrazepam CRS.<\/p>\n

TESTS<\/h2>\n

Loss on drying (2.2.32)<\/h4>\nMaximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 4 h.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\nDissolve 0.250 g in 25 mL of acetic anhydride R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).<\/p>\n1 mL of 0.1 M perchloric acid is equivalent to 28.13 mg of C15<\/sub>H11<\/sub>N3<\/sub>O3<\/sub>.<\/p>\n

STORAGE<\/h2>\nProtected from light.<\/p>\n

Content<\/h3>\n
99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

Appearance<\/h3>\n
White or yellow, crystalline powder.<\/p>\n

Solubility<\/h3>\n
Practically insoluble in water, slightly soluble in ethanol (96 per cent).<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: nitrazepam CRS.<\/p>\n

Loss on drying (2.2.32)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \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 0.250 g in 25 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 28.13 mg of C_{15<\/sub>H_{11<\/sub>N_{3<\/sub>O_{3<\/sub>.<\/p>\n}}}}

STORAGE<\/h2>\n
Protected from light.<\/p>\n