{"id":25453,"date":"2025-11-04T14:59:50","date_gmt":"2025-11-04T07:59:50","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=25453"},"modified":"2025-11-04T14:59:50","modified_gmt":"2025-11-04T07:59:50","slug":"norgestimate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/norgestimate\/","title":{"rendered":"Norgestimate"},"content":{"rendered":"

(Ph. Eur. monograph 1732)<\/em><\/p>\n

C23<\/sub>H31<\/sub>NO3<\/sub> 369.5 35189-28-7<\/p>\n

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

Progestogen.<\/p>\n

DEFINITION<\/h2>\n

(3EZ)-13\u03b2-Ethyl-3-(hydroxyimino)-18,19-dinor-17\u03b1-pregn-4-en-20-yn-17-yl acetate.<\/p>\n

Content<\/h3>\n

98.5 per cent to 101.5 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Practically insoluble in water, freely soluble in methylene chloride, soluble in acetone.<\/p>\n

IDENTIFICATION<\/h2>\n

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

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

TESTS<\/h2>\n

Specific optical rotation (2.2.7)<\/h3>\n

+ 42.0 to + 50.0 (dried substance).<\/p>\n

Dissolve 0.200 g in methylene chloride R and dilute to 20.0 mL with the same solvent.<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29).<\/p>\n

Solvent mixture water R, methanol R (1:4 V\/V).<\/p>\n

Test solution: Dissolve 25.0 mg of the substance to be examined in the solvent mixture and dilute to 50.0 mL with the solvent mixture.<\/p>\n

Reference solution (a): Dilute 2.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 20.0 mL with the solvent mixture.<\/p>\n

Reference solution (b): Dissolve 2 mg of norgestimate for system suitability CRS (containing impurity A) in 4 mL of the solvent mixture.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.10 m, \u00d8 = 4.6 mm;<\/p>\n

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

\u2014 temperature: 40 \u00b0C.<\/p>\n

Mobile phase: acetonitrile R, tetrahydrofuran for chromatography R, water R (18:22:60 V\/V\/V).<\/p>\n

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

Detection: Spectrophotometer at 244 nm.<\/p>\n

Injection: 25 \u03bcL.<\/p>\n

Run time: Twice the retention time of the (E)-isomer of norgestimate.<\/p>\n

Identification of impurities: Use the chromatogram supplied with norgestimate for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peak due to impurity A.<\/p>\n

Relative retention: With reference to the (E)-isomer of norgestimate (retention time = about 14 min): impurity A = about 0.7; (Z)-isomer of norgestimate = about 0.9.<\/p>\n

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

\u2014 resolution: minimum 1.5 between the peaks due to the (E)- and (Z)-isomers of norgestimate.<\/p>\n

Limits:<\/p>\n

\u2014 correction factor: for the calculation of content, multiply the peak area of the (Z)-isomer of norgestimate by 1.33;<\/p>\n

\u2014 impurity A: not more than twice the sum of the areas of the peaks due to the (E)- and (Z)-isomers of norgestimate in the chromatogram obtained with reference solution (a) (0.2 per cent);<\/p>\n

\u2014 unspecified impurities: for each impurity, not more than the sum of the areas of the peaks due to the (E)- and (Z)-isomers of norgestimate in the chromatogram obtained with reference solution (a) (0.10 per
\ncent);<\/p>\n

\u2014 total: not more than 3 times the sum of the areas of the peaks due to the (E)- and (Z)-isomers of norgestimate in the chromatogram obtained with reference solution (a) (0.3 per cent);<\/p>\n

\u2014 disregard limit: 0.5 times the sum of the areas of the peaks due to the (E)- and (Z)-isomers of norgestimate in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n

Ratio of (E)- to (Z)-isomers<\/h3>\n

Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n

Injection: Test solution.<\/p>\n

Calculate the (E)- to (Z)-isomer ratio by dividing the area of the peak due to the (E)-isomer by 1.33 times the area of the peak due to the (Z)-isomer. The ratio is 1.27 to 1.78.<\/p>\n

Loss on drying (2.2.32)<\/h3>\n

Maximum 0.5 per cent, determined on 0.500 g by drying in an oven at 105 \u00b0C for 3 h.<\/p>\n

ASSAY<\/h2>\n

Dissolve 0.300 g in 40 mL of tetrahydrofuran R. Add 10 mL of a 100 g\/L solution of silver nitrate R and titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20). Rinse the electrode with
\nacetone R after each titration.<\/p>\n

If necessary, after several titrations re-equilibrate the electrode in water R for 15 min to obtain sharper titration curves.<\/p>\n

1 mL of 0.1 M sodium hydroxide is equivalent to 36.95 mg of C23<\/sub>H31<\/sub>NO3<\/sub>.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A.<\/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
\nother\/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.<\/p>\n

Control of impurities in substances for pharmaceutical use) B, C, D.<\/p>\n

\"Norgestimate<\/p>\n

A. 13\u03b2-ethyl-3-oxo-18,19-dinor-17\u03b1-pregn-4-en-20-yn-17-yl acetate (levonorgestrel acetate),<\/p>\n

\"Norgestimate<\/p>\n

B. 13\u03b2-ethyl-17\u03b2-hydroxy-18,19-dinor-17\u03b1-pregn-4-en-20-yn-3-one (levonorgestrel),<\/p>\n

\"Norgestimate<\/p>\n

C. (3E)-13\u03b2-ethyl-3-(hydroxyimino)-18,19-dinor-17\u03b1-pregn-4-en-20-yn-17-ol ((E)-norelgestromin),<\/p>\n

\"Norgestimate<\/p>\n

D. (3Z)-13\u03b2-ethyl-3-(hydroxyimino)-18,19-dinor-17\u03b1-pregn-4-en-20-yn-17-ol ((Z)-norelgestromin).<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 1732) C23H31NO3 369.5 35189-28-7 Action and use Progestogen. DEFINITION (3EZ)-13\u03b2-Ethyl-3-(hydroxyimino)-18,19-dinor-17\u03b1-pregn-4-en-20-yn-17-yl acetate. Content 98.5 per cent to 101.5 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Practically insoluble in water, freely soluble in methylene chloride, soluble in acetone. IDENTIFICATION Infrared absorption spectrophotometry (2.2.24). Comparison: norgestimate CRS. TESTS Specific optical…<\/p>\n","protected":false},"author":4,"featured_media":25477,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25453","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\/25453","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=25453"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25453\/revisions"}],"predecessor-version":[{"id":25486,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25453\/revisions\/25486"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25477"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25453"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25453"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25453"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}