{"id":10459,"date":"2025-10-08T09:43:58","date_gmt":"2025-10-08T02:43:58","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=10459"},"modified":"2025-10-08T09:44:58","modified_gmt":"2025-10-08T02:44:58","slug":"drospirenone","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/drospirenone\/","title":{"rendered":"Drospirenone"},"content":{"rendered":"

(Ph. Eur. monograph 2404)<\/p>\n

C24<\/sub>H30<\/sub>O3<\/sub>\u00a0 \u00a0366.5\u00a0 \u00a067392-87-4<\/p>\n

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

Aldosterone receptor antagonist.<\/p>\n

DEFINITION<\/h2>\n

3-Oxo-6\u03b1,7\u03b1,15\u03b1,16\u03b1-tetrahydro-3\u2032H,3\u2032\u2032H-dicyclopropa[6,7:15,16]-17\u03b1-pregn-4-en-21,17-carbolactone.<\/p>\n

Content<\/h3>\n

98.0 per cent to 102.0 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 methanol, sparingly soluble in ethanol (96 per cent).<\/p>\n

IDENTIFICATION<\/h2>\n

A. Specific optical rotation (see Tests).<\/p>\n

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

Comparison drospirenone CRS.<\/p>\n

TESTS<\/h2>\n

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

-193 to -187 (dried substance).<\/p>\n

Dissolve 0.100 g in methanol R and dilute to 10.0 mL with the same solvent.<\/p>\n

Related substances<\/h3>\n

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

Solvent mixture acetonitrile R, water R (50:50 V\/V).<\/p>\n

Test solution: Dissolve 30.0 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 1.0 mL of the test solution to 10.0 mL with the solvent mixture. Use 1.0 mL of this solution to dissolve the contents of a vial of drospirenone impurity E CRS.<\/p>\n

Reference solution (b): Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n

Reference solution (c): Dissolve 30.0 mg of drospirenone CRS in the solvent mixture and dilute to 50.0 mL with the solvent mixture.<\/p>\n

Reference solution (d): Dissolve 3 mg of drospirenone for peak identification CRS (containing impurity A) in the solvent mixture and dilute to 5.0 mL with the solvent mixture.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (3 \u03bcm);<\/p>\n

\u2014 temperature: 35 \u00b0C.<\/p>\n

Mobile phase:<\/p>\n

\u2014 mobile phase A: water R;<\/p>\n

\u2014 mobile phase B: acetonitrile R;<\/p>\n\n\n\n\n\n\n\n\n
Time
\n(min)<\/td>\n		Mobile phase A
\n(per cent V\/V)<\/td>\n		Mobile phase B
\n(per cent V\/V)<\/td>\n<\/tr>\n
0 – 2<\/td>\n63<\/td>\n37<\/td>\n<\/tr>\n
2 – 16<\/td>\n\u00a063 \u2192 52<\/td>\n\u00a037 \u2192 48<\/td>\n<\/tr>\n
16 – 23<\/td>\n52<\/td>\n48<\/td>\n<\/tr>\n
23 – 31<\/td>\n\u00a052 \u2192 20<\/td>\n\u00a048 \u2192 80<\/td>\n<\/tr>\n
31 – 39<\/td>\n20<\/td>\n80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

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

Detection: Spectrophotometer at 245 nm.<\/p>\n

Injection 10 \u03bcL of the test solution and reference solutions (a), (b) and (d).<\/p>\n

Identification of impurities: Use the chromatogram supplied with drospirenone for peak identification CRS and the chromatogram obtained with reference solution (d) to identify the peak due to impurity A; use the chromatogram obtained with reference solution (a) to identify the peak due to impurity E.<\/p>\n

Relative retention With reference to drospirenone (retention time = about 22 min): impurity E = about 1.1;
\nimpurity A = about 1.2.<\/p>\n

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

\u2014 resolution: minimum 5.0 between the peaks due to drospirenone and impurity E.<\/p>\n

Limits:<\/p>\n

\u2014 correction factor: for the calculation of content, multiply the peak area of impurity A by 0.5;<\/p>\n

\u2014 impurity A: not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.15 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 (b) (0.10 per cent);<\/p>\n

\u2014 total: not more than 3 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n

\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (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 3 h.<\/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 Test solution and reference solution (c).<\/p>\n

Calculate the percentage content of C24<\/sub>H30<\/sub>O3<\/sub> taking into account the assigned content of drospirenone CRS.<\/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 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) B, C, D, E, F,G, H, I, K.<\/p>\n

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

A. 3-oxo-15\u03b1,16\u03b1-dihydro-3\u2032H-cyclopropa[15,16]-17\u03b1-pregn-4-ene-21,17-carbolactone (6,7-desmethylenedrospirenone),<\/p>\n

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

B. 7\u03b2-(hydroxymethyl)-3-oxo-15\u03b1,16\u03b1-dihydro-3\u2032H-cyclopropa[15,16]-17\u03b1-pregn-4-ene-21,17-carbolactone (7\u03b2-hydroxymethyl derivative),<\/p>\n

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

C. 6\u03b1,7\u03b1,15\u03b1,16\u03b1-tetrahydro-3\u2032H,3\u2032\u2032H -dicyclopropa[6,7:15,16]androst-4-ene-3,17-dione (17-keto derivative),<\/p>\n

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

D. 3-oxo-15\u03b1,16\u03b1-dihydro-3\u2032H-cyclopropa[15,16]-17\u03b1-pregna-4,6-diene-21,17-carbolactone (\u03946-drospirenone),<\/p>\n

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

E. 3-oxo-6\u03b1,7\u03b1,15\u03b1,16\u03b1-tetrahydro-3\u2032H,3\u2032\u2032H dicyclopropa[6,7:15,16]pregn-4-ene-21,17-carbolactone (17-
\nepidrospirenone),<\/p>\n

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

F. 15\u03b2-methyl-3-oxo-6\u03b1,7\u03b1-dihydro-3\u2032H-cyclopropa[6,7]-17\u03b1-pregn-4-ene-21,17-carbolactone (3\u2032\u2032-16-secodrospirenone),<\/p>\n

\"Drospirenone-7\"<\/p>\n

G. 7\u03b2-(chloromethyl)-3-oxo-15\u03b1,16\u03b1-dihydro-3\u2032H-cyclopropa[15,16]-17\u03b1-pregn-4-ene-21,17-carbolactone (3\u2032-chloro-3\u2032,6-secodrospirenone),<\/p>\n

\"Drospirenone-8\"<\/p>\n

H. 7\u03b2-(chloromethyl)-3-oxo-15\u03b1,16\u03b1-dihydro-3\u2032H-cyclopropa[15,16]pregn-4-ene-21,17-carbolactone (3\u2032-chloro-3\u2032,6-seco-17-epidrospirenone),<\/p>\n

\"Drospirenone-9\"<\/p>\n

I. 7\u03b2-(hydroxymethyl)-15\u03b1,16\u03b1-dihydro-3\u2032H-cyclopropa[15,16]-17\u03b1-pregna-3,5-diene-21,17-carbolactone (7\u03b2-hydroxymethyldiene derivative),<\/p>\n

\"Drospirenone-10\"<\/p>\n

K. 3-oxo-6\u03b2,7\u03b2,15\u03b1,16\u03b1-tetrahydro-3\u2032H,3\u2032\u2032H-dicyclopropa[6,7:15,16]-17\u03b1-pregn-4-ene-21,17-carbolactone (6\u03b1,7\u03b1-drospirenone).<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 2404) C24H30O3\u00a0 \u00a0366.5\u00a0 \u00a067392-87-4 Action and use Aldosterone receptor antagonist. DEFINITION 3-Oxo-6\u03b1,7\u03b1,15\u03b1,16\u03b1-tetrahydro-3\u2032H,3\u2032\u2032H-dicyclopropa[6,7:15,16]-17\u03b1-pregn-4-en-21,17-carbolactone. Content 98.0 per cent to 102.0 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Practically insoluble in water, freely soluble in methylene chloride, soluble in methanol, sparingly soluble in ethanol (96 per cent). IDENTIFICATION A. Specific…<\/p>\n","protected":false},"author":3,"featured_media":10479,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-10459","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\/10459","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=10459"}],"version-history":[{"count":3,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/10459\/revisions"}],"predecessor-version":[{"id":10484,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/10459\/revisions\/10484"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/10479"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=10459"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=10459"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=10459"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}