{"id":26095,"date":"2025-11-05T11:26:47","date_gmt":"2025-11-05T04:26:47","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=26095"},"modified":"2025-11-06T09:36:12","modified_gmt":"2025-11-06T02:36:12","slug":"nevirapine-hemihydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/nevirapine-hemihydrate\/","title":{"rendered":"Nevirapine Hemihydrate"},"content":{"rendered":"

Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n

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

Non-nucleoside reverse transcriptase inhibitor; antiviral (HIV).<\/p>\n

Preparation<\/strong><\/p>\n

Nevirapine Oral Suspension<\/p>\n

Ph Eur<\/p>\n

\n
DEFINITION<\/h2>\n
11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one\u00a0 hemihydrate.<\/p>\n
Content<\/strong><\/p>\n
97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, slightly soluble in methanol and in methylene chloride.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison\u00a0 nevirapine hemihydrate CRS.<\/p>\n
B. Water (see Tests).<\/p>\n
TESTS<\/h2>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Test solution\u00a0 Dissolve 20.0 mg of the substance to be examined in methanol R and sonicate until dissolution is complete. Dilute to 50.0 mL with methanol R.<\/p>\n
Reference solution (a)\u00a0 Dilute 1.0 mL of the test solution to 100.0 mL with methanol R. Dilute 1.0 mL of this solution to 10.0 mL with methanol R.<\/p>\n
Reference solution (b)\u00a0 Add 1 mL of methanol R to a vial of nevirapine for peak identification CRS
\n(containing impurities A, B and C), mix and sonicate for 1 min.<\/p>\n
Reference solution (c)\u00a0 Dissolve 20.0 mg of anhydrous nevirapine CRS in methanol R and sonicate until dissolution is complete. Dilute to 50.0 mL with methanol R.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 50 mm, \u00d8 = 2.1 mm;<\/p>\n
\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography compatible with 100 per cent aqueous mobile phases R (1.8 \u00b5m);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: dissolve 0.77 g of ammonium acetate R in 900 mL of water for chromatography R, adjust to pH 5.6 with acetic acid R and dilute to 1000 mL with water for chromatography R;<\/p>\n
\u2014 mobile phase B: acetonitrile R;<\/p>\n\n\n\n\n\n\n\n
Time (min)<\/strong><\/td>\n Mobile phase A (per cent V\/V)<\/strong><\/td>\n Mobile phase B (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 \u2013 1.35<\/td>\n 90<\/td>\n 10<\/td>\n<\/tr>\n
1.35 \u2013 3.85<\/td>\n 90 \u2192 67<\/td>\n 10 \u2192 33<\/td>\n<\/tr>\n
3.85 \u2013 6.70<\/td>\n 67 \u2192 60<\/td>\n 33 \u2192 40<\/td>\n<\/tr>\n
6.70 \u2013 7.65<\/td>\n 60<\/td>\n 40<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate\u00a0 0.7 mL\/min.<\/p>\n
Detection\u00a0 Spectrophotometer at 282 nm.<\/p>\n
Injection\u00a0 2.0 \u00b5L of the test solution and reference solutions (a) and (b).<\/p>\n
Identification of impurities\u00a0 Use the chromatogram supplied with nevirapine for peak identification CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B and C.<\/p>\n
Relative retention\u00a0 With reference to nevirapine (retention time = about 3 min): impurity B = about 0.9; impurity A = about 1.2; impurity C = about 1.3.<\/p>\n
System suitability:<\/p>\n
\u2014 resolution: minimum 5.0 between the peaks due to impurity B and nevirapine and minimum 5.0 between the peaks due to nevirapine and impurity A in the chromatogram obtained with reference solution (b);<\/p>\n
\u2014 symmetry factor: maximum 1.7 for the peak due to nevirapine in the chromatogram obtained with reference solution (a).<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of nevirapine hemihydrate in reference solution (a).<\/p>\n
Limits:<\/p>\n
\u2014 impurities A, B, C: for each impurity, maximum 0.2 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 0.6 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Water (2.5.12)<\/strong><\/p>\n
3.1 per cent to 3.9 per cent, determined on 0.300 g.<\/p>\n
Sulfated ash (2.4.14)<\/strong><\/p>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n
Injection\u00a0 2.0 \u00b5L of the test solution and reference solution (c).<\/p>\n
Calculate the percentage content of C_{15<\/sub>H_{14<\/sub>N_{4<\/sub>O taking into account the assigned content of anhydrous nevirapine CRS.<\/p>\n}}}
IMPURITIES<\/h2>\n
Specified impurities\u00a0 A, B, C.<\/em><\/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.<\/em><\/p>\n
Control of impurities in substances for pharmaceutical use)\u00a0 D.<\/em><\/p>\n
$\"Nevirapine$ <\/p>\n
A. 11-ethyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one,<\/p>\n
$\"Nevirapine$ <\/p>\n
B. 4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one,<\/p>\n
$\"Nevirapine$ <\/p>\n
C. 4-methyl-11-propyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one,<\/p>\n
$\"Nevirapine$ <\/p>\n
D. 11,11\u2032-dicyclopropyl-4,4\u2032-dimethyl-5,5\u2032,11,11\u2032-tetrahydro-6H,6\u2032H-9,9\u2032-bidipyrido[3,2-b:2\u2032,3\u2032-e]\u00a0 [1,4]diazepine-6,6\u2032-dione.<\/p>\n
\n
Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Non-nucleoside reverse transcriptase inhibitor; antiviral (HIV). Preparation Nevirapine Oral Suspension Ph Eur DEFINITION 11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one\u00a0 hemihydrate. Content 97.5 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white powder. Solubility Practically insoluble in water, slightly soluble in methanol and in methylene chloride….<\/p>\n","protected":false},"author":5,"featured_media":26130,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26095","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\/26095","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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=26095"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26095\/revisions"}],"predecessor-version":[{"id":26746,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26095\/revisions\/26746"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26130"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26095"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26095"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26095"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time (min)<\/strong><\/td>\n	Mobile phase A (per cent V\/V)<\/strong><\/td>\n	Mobile phase B (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 \u2013 1.35<\/td>\n	90<\/td>\n	10<\/td>\n<\/tr>\n
1.35 \u2013 3.85<\/td>\n	90 \u2192 67<\/td>\n	10 \u2192 33<\/td>\n<\/tr>\n
3.85 \u2013 6.70<\/td>\n	67 \u2192 60<\/td>\n	33 \u2192 40<\/td>\n<\/tr>\n
6.70 \u2013 7.65<\/td>\n	60<\/td>\n	40<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate\u00a0 0.7 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 282 nm.<\/p>\n Injection\u00a0 2.0 \u00b5L of the test solution and reference solutions (a) and (b).<\/p>\n Identification of impurities\u00a0 Use the chromatogram supplied with nevirapine for peak identification CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B and C.<\/p>\n Relative retention\u00a0 With reference to nevirapine (retention time = about 3 min): impurity B = about 0.9; impurity A = about 1.2; impurity C = about 1.3.<\/p>\n System suitability:<\/p>\n \u2014 resolution: minimum 5.0 between the peaks due to impurity B and nevirapine and minimum 5.0 between the peaks due to nevirapine and impurity A in the chromatogram obtained with reference solution (b);<\/p>\n \u2014 symmetry factor: maximum 1.7 for the peak due to nevirapine in the chromatogram obtained with reference solution (a).<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for each impurity, use the concentration of nevirapine hemihydrate in reference solution (a).<\/p>\n Limits:<\/p>\n \u2014 impurities A, B, C: for each impurity, maximum 0.2 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 0.6 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent.<\/p>\n Water (2.5.12)<\/strong><\/p>\n 3.1 per cent to 3.9 per cent, determined on 0.300 g.<\/p>\n Sulfated ash (2.4.14)<\/strong><\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n ASSAY<\/h2>\n Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n Injection\u00a0 2.0 \u00b5L of the test solution and reference solution (c).<\/p>\n Calculate the percentage content of C_{15<\/sub>H_{14<\/sub>N_{4<\/sub>O taking into account the assigned content of anhydrous nevirapine CRS.<\/p>\n}}} IMPURITIES<\/h2>\n Specified impurities\u00a0 A, B, C.<\/em><\/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.<\/em><\/p>\n Control of impurities in substances for pharmaceutical use)\u00a0 D.<\/em><\/p>\n $\"Nevirapine$ <\/p>\n A. 11-ethyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one,<\/p>\n $\"Nevirapine$ <\/p>\n B. 4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one,<\/p>\n $\"Nevirapine$ <\/p>\n C. 4-methyl-11-propyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one,<\/p>\n $\"Nevirapine$ <\/p>\n D. 11,11\u2032-dicyclopropyl-4,4\u2032-dimethyl-5,5\u2032,11,11\u2032-tetrahydro-6H,6\u2032H-9,9\u2032-bidipyrido[3,2-b:2\u2032,3\u2032-e]\u00a0 [1,4]diazepine-6,6\u2032-dione.<\/p>\n \n Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Non-nucleoside reverse transcriptase inhibitor; antiviral (HIV). Preparation Nevirapine Oral Suspension Ph Eur DEFINITION 11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one\u00a0 hemihydrate. Content 97.5 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white powder. Solubility Practically insoluble in water, slightly soluble in methanol and in methylene chloride….<\/p>\n","protected":false},"author":5,"featured_media":26130,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26095","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\/26095","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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=26095"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26095\/revisions"}],"predecessor-version":[{"id":26746,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26095\/revisions\/26746"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26130"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26095"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26095"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26095"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

DEFINITION<\/h2>\n11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one\u00a0 hemihydrate.<\/p>\nContent<\/strong><\/p>\n97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

Appearance<\/h3>\nWhite or almost white powder.<\/p>\n

Solubility<\/h3>\nPractically insoluble in water, slightly soluble in methanol and in methylene chloride.<\/p>\n

IDENTIFICATION<\/h2>\nA. Infrared absorption spectrophotometry (2.2.24).<\/p>\nComparison\u00a0 nevirapine hemihydrate CRS.<\/p>\nB. Water (see Tests).<\/p>\n

TESTS<\/h2>\n

DEFINITION<\/h2>\n
11-Cyclopropyl-4-methyl-5,11-dihydro-6H-dipyrido[3,2-b:2\u2032,3\u2032-e][1,4]diazepin-6-one\u00a0 hemihydrate.<\/p>\n
Content<\/strong><\/p>\n
97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

Appearance<\/h3>\n
White or almost white powder.<\/p>\n

Solubility<\/h3>\n
Practically insoluble in water, slightly soluble in methanol and in methylene chloride.<\/p>\n

IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison\u00a0 nevirapine hemihydrate CRS.<\/p>\n
B. Water (see Tests).<\/p>\n