{"id":12164,"date":"2025-10-10T16:37:33","date_gmt":"2025-10-10T09:37:33","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=12164"},"modified":"2025-10-10T16:37:33","modified_gmt":"2025-10-10T09:37:33","slug":"eplerenone","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/eplerenone\/","title":{"rendered":"Eplerenone"},"content":{"rendered":"

(Ph. Eur. monograph 2765)<\/p>\n

C_{24<\/sub>H_{30<\/sub>O_{6<\/sub>\u00a0 \u00a0 \u00a0 \u00a0414.5\u00a0 \u00a0 \u00a0 \u00a0 107724-20-9<\/p>\n}}}

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

Aldosterone receptor antagonist; antihypertensive.<\/p>\n

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

Eplerenone Tablets<\/p>\n

DEFINITION<\/h2>\n
9,11\u03b1-Epoxy-7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone.<\/p>\n
Content<\/h3>\n
97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White, almost white or slightly yellow, crystalline powder.<\/p>\n
Solubility<\/h3>\n
Slightly soluble in water, freely soluble in methylene chloride, slightly soluble in ethanol (96 per cent).<\/p>\n
It shows polymorphism (5.9).<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: eplerenone CRS.<\/p>\n
If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in methanol R, evaporate to dryness and record new spectra using the residues.<\/p>\n
TESTS<\/h2>\n
Specific optical rotation (2.2.7)<\/h3>\n
-16.0 to -14.0.<\/p>\n
Dissolve 0.250 g in acetonitrile R and dilute to 25.0 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Solvent mixture: acetonitrile R, methanol R, water R (25:25:50 V\/V\/V).<\/p>\n
Test solution (a): 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
Test solution (b): Dilute 1.0 mL of test solution (a) to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): Dissolve 5 mg of eplerenone for system suitability CRS (containing impurities A and D) in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (b): Dissolve 5 mg of eplerenone for peak identification CRS (containing impurity B) in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (c): Dilute 1.0 mL of test solution (a) 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 (d): Dissolve 25.0 mg of eplerenone CRS in the solvent mixture and dilute to 50.0 mL with the solvent mixture. Dilute 1.0 mL of the solution to 10.0 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: base-deactivated end-capped octadecylsilyl silica gel for chromatography R (3 \u03bcm);<\/p>\n
\u2014 temperature: 30 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: 0.1 per cent V\/V solution of phosphoric acid R;<\/p>\n
\u2014 mobile phase B: phosphoric acid R, acetonitrile R, methanol R (0.1:40:60 V\/V\/V);<\/p>\n
<\/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 – 25<\/td>\n 54<\/td>\n 46<\/td>\n<\/tr>\n
25 – 32<\/td>\n 54 \u2192 40<\/td>\n 46 \u2192 60<\/td>\n<\/tr>\n
32 – 45<\/td>\n 40<\/td>\n 60<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 240 nm.<\/p>\n
Injection: 20 \u03bcL of test solution (a) and reference solutions (a), (b) and (c).<\/p>\n
Identification of impurities: Use the chromatogram supplied with eplerenone for system suitability CRS and the
\nchromatogram obtained with reference solution (a) to identify the peaks due to impurities A and D; use the chromatogram supplied with eplerenone for peak identification CRS and the chromatogram obtained with reference solution (b) to identify the peak due to impurity B.<\/p>\n
Relative retention: With reference to eplerenone (retention time = about 9 min): impurity D = about 0.71;
\nimpurity A = about 0.74; impurity B = about 1.2.<\/p>\n
System suitability: Reference solution (a):<\/p>\n
\u2014 peak-to-valley ratio: minimum 5.0, where Hp = height above the baseline of the peak due to impurity D and H_{v<\/sub> = height above the baseline of the lowest point of the curve separating this peak from the peak due to impurity A.<\/p>\n}
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of eplerenone in reference solution (c).<\/p>\n
Limits:<\/p>\n
\u2014 impurities A, B: for each impurity, maximum 0.3 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)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 g.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\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: Test solution (b) and reference solution (d).<\/p>\n
Calculate the percentage content of C_{24<\/sub>H_{30<\/sub>O_{6<\/sub> taking into account the assigned content of eplerenone CRS.<\/p>\n}}}
IMPURITIES<\/h2>\n
Specified impurities A, B.<\/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, E, F, G.<\/p>\n
$\"Eplerenone\"$ <\/p>\n
A. 3-oxo-17\u03b1-pregn-4-ene-7\u03b1,9:21,17-dicarbolactone,<\/p>\n
$\"Eplerenone\"$ <\/p>\n
B. 11\u03b1,12\u03b1-epoxy-7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone,<\/p>\n
$\"Eplerenone\"$ <\/p>\n
C. 7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregna-4,9(11)-diene-21,17-carbolactone,<\/p>\n
$\"Eplerenone\"$ <\/p>\n
D. (2\u2032R)-9,11\u03b1-epoxy-3,5\u2032-dioxo-4\u2032,5\u2032-dihydro-3\u2032H-spiro[androst-4-ene-17,2\u2032-furan]-7\u03b1-carboxylic acid,<\/p>\n
$\"Eplerenone\"$ <\/p>\n
E. 9,11\u03b1-epoxy-7\u03b2-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone,<\/p>\n
$\"Eplerenone\"$ <\/p>\n
F. 9,11\u03b1-epoxy-17-hydroxy-7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21-carboxylic acid,<\/p>\n
$\"Eplerenone\"$ <\/p>\n
G. 7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 2765) C24H30O6\u00a0 \u00a0 \u00a0 \u00a0414.5\u00a0 \u00a0 \u00a0 \u00a0 107724-20-9 Action and use Aldosterone receptor antagonist; antihypertensive. Preparation Eplerenone Tablets DEFINITION 9,11\u03b1-Epoxy-7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone. Content 97.5 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White, almost white or slightly yellow, crystalline powder. Solubility Slightly soluble in water, freely soluble in methylene chloride, slightly…<\/p>\n","protected":false},"author":2,"featured_media":12201,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-12164","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\/12164","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=12164"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12164\/revisions"}],"predecessor-version":[{"id":12203,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12164\/revisions\/12203"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/12201"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=12164"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=12164"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=12164"}],"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 – 25<\/td>\n	54<\/td>\n	46<\/td>\n<\/tr>\n
25 – 32<\/td>\n	54 \u2192 40<\/td>\n	46 \u2192 60<\/td>\n<\/tr>\n
32 – 45<\/td>\n	40<\/td>\n	60<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 1.0 mL\/min.<\/p>\n Detection: Spectrophotometer at 240 nm.<\/p>\n Injection: 20 \u03bcL of test solution (a) and reference solutions (a), (b) and (c).<\/p>\n Identification of impurities: Use the chromatogram supplied with eplerenone for system suitability CRS and the \nchromatogram obtained with reference solution (a) to identify the peaks due to impurities A and D; use the chromatogram supplied with eplerenone for peak identification CRS and the chromatogram obtained with reference solution (b) to identify the peak due to impurity B.<\/p>\n Relative retention: With reference to eplerenone (retention time = about 9 min): impurity D = about 0.71; \nimpurity A = about 0.74; impurity B = about 1.2.<\/p>\n System suitability: Reference solution (a):<\/p>\n \u2014 peak-to-valley ratio: minimum 5.0, where Hp = height above the baseline of the peak due to impurity D and H_{v<\/sub> = height above the baseline of the lowest point of the curve separating this peak from the peak due to impurity A.<\/p>\n} Calculation of percentage contents:<\/p>\n \u2014 for each impurity, use the concentration of eplerenone in reference solution (c).<\/p>\n Limits:<\/p>\n \u2014 impurities A, B: for each impurity, maximum 0.3 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)<\/h4>\n Maximum 0.5 per cent, determined on 1.000 g.<\/p>\n Sulfated ash (2.4.14)<\/h4>\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: Test solution (b) and reference solution (d).<\/p>\n Calculate the percentage content of C_{24<\/sub>H_{30<\/sub>O_{6<\/sub> taking into account the assigned content of eplerenone CRS.<\/p>\n}}} IMPURITIES<\/h2>\n Specified impurities A, B.<\/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, E, F, G.<\/p>\n $\"Eplerenone\"$ <\/p>\n A. 3-oxo-17\u03b1-pregn-4-ene-7\u03b1,9:21,17-dicarbolactone,<\/p>\n $\"Eplerenone\"$ <\/p>\n B. 11\u03b1,12\u03b1-epoxy-7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone,<\/p>\n $\"Eplerenone\"$ <\/p>\n C. 7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregna-4,9(11)-diene-21,17-carbolactone,<\/p>\n $\"Eplerenone\"$ <\/p>\n D. (2\u2032R)-9,11\u03b1-epoxy-3,5\u2032-dioxo-4\u2032,5\u2032-dihydro-3\u2032H-spiro[androst-4-ene-17,2\u2032-furan]-7\u03b1-carboxylic acid,<\/p>\n $\"Eplerenone\"$ <\/p>\n E. 9,11\u03b1-epoxy-7\u03b2-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone,<\/p>\n $\"Eplerenone\"$ <\/p>\n F. 9,11\u03b1-epoxy-17-hydroxy-7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21-carboxylic acid,<\/p>\n $\"Eplerenone\"$ <\/p>\n G. 7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 2765) C24H30O6\u00a0 \u00a0 \u00a0 \u00a0414.5\u00a0 \u00a0 \u00a0 \u00a0 107724-20-9 Action and use Aldosterone receptor antagonist; antihypertensive. Preparation Eplerenone Tablets DEFINITION 9,11\u03b1-Epoxy-7\u03b1-(methoxycarbonyl)-3-oxo-17\u03b1-pregn-4-ene-21,17-carbolactone. Content 97.5 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White, almost white or slightly yellow, crystalline powder. Solubility Slightly soluble in water, freely soluble in methylene chloride, slightly…<\/p>\n","protected":false},"author":2,"featured_media":12201,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-12164","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\/12164","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=12164"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12164\/revisions"}],"predecessor-version":[{"id":12203,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12164\/revisions\/12203"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/12201"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=12164"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=12164"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=12164"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

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

Solubility<\/h3>\nSlightly soluble in water, freely soluble in methylene chloride, slightly soluble in ethanol (96 per cent).<\/p>\nIt shows polymorphism (5.9).<\/p>\n

TESTS<\/h2>\n

Specific optical rotation (2.2.7)<\/h3>\n-16.0 to -14.0.<\/p>\nDissolve 0.250 g in acetonitrile R and dilute to 25.0 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\nMaximum 0.5 per cent, determined on 1.000 g.<\/p>\n

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

Content<\/h3>\n
97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

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

Solubility<\/h3>\n
Slightly soluble in water, freely soluble in methylene chloride, slightly soluble in ethanol (96 per cent).<\/p>\n
It shows polymorphism (5.9).<\/p>\n

Specific optical rotation (2.2.7)<\/h3>\n
-16.0 to -14.0.<\/p>\n
Dissolve 0.250 g in acetonitrile R and dilute to 25.0 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 g.<\/p>\n

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