{"id":26004,"date":"2025-11-05T10:22:42","date_gmt":"2025-11-05T03:22:42","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=26004"},"modified":"2025-11-05T10:22:42","modified_gmt":"2025-11-05T03:22:42","slug":"olmesartan-medoxomil","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/olmesartan-medoxomil\/","title":{"rendered":"Olmesartan Medoxomil"},"content":{"rendered":"

(Ph. Eur. monograph 2600)<\/p>\n

C_{29<\/sub>H_{30<\/sub>N_{6<\/sub>O_{6<\/sub> 558.6 144689-63-4<\/p>\n}}}}

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

Angiotensin II (AT_{1<\/sub>) receptor antagonist.<\/p>\n}

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

Olmesartan Tablets<\/p>\n

DEFINITION<\/h2>\n
(5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2\u2032-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylate.<\/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 or almost white, crystalline powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, slightly soluble in ethanol (96 per cent), practically insoluble in heptane.<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: olmesartan medoxomil CRS.<\/p>\n
TESTS<\/h2>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Test solution (a): Dissolve 25 mg of the substance to be examined in acetonitrile R and dilute to 25.0 mL with the same solvent.<\/p>\n
Test solution (b): Dissolve 25.0 mg of the substance to be examined in acetonitrile R and dilute to 50.0 mL with the same solvent.<\/p>\n
Reference solution (a): Dissolve 5 mg of olmesartan medoxomil for system suitability CRS (containing impurities A, B and C) in acetonitrile R and dilute to 5 mL with the same solvent.<\/p>\n
Reference solution (b): Dilute 1.0 mL of test solution (a) to 50.0 mL with acetonitrile R. Dilute 1.0 mL of this solution to 10.0 mL with acetonitrile R.<\/p>\n
Reference solution (c): Dissolve 25.0 mg of olmesartan medoxomil CRS in acetonitrile R and dilute to 50.0 mL with the same solvent.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.10 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped octylsilyl silica gel for chromatography R (3.5 \u03bcm);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: mix 20 volumes of acetonitrile R and 80 volumes of a 2.04 g\/L solution of potassium dihydrogen phosphate R previously adjusted to pH 3.4 with a 1.73 g\/L solution of phosphoric acid R;<\/p>\n
\u2014 mobile phase B: mix 20 volumes of a 2.04 g\/L solution of potassium dihydrogen phosphate R, previously adjusted to pH 3.4 with a 1.73 g\/L solution of phosphoric acid R, and 80 volumes of 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 – 10<\/td>\n 75<\/td>\n 25<\/td>\n<\/tr>\n
10 – 35<\/td>\n 75 \u2192 0<\/td>\n 25 \u2192 100<\/td>\n<\/tr>\n
35 – 45<\/td>\n 0<\/td>\n 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 250 nm.<\/p>\n
Injection: 10 \u03bcL of test solution (a) and reference solutions (a) and (b).<\/p>\n
Identification of impurities: Use the chromatogram supplied with olmesartan medoxomil for system suitability CRS and the chromatogram obtained with reference solution (a) to identify the peaks due to
\nimpurities A, B and C.<\/p>\n
Relative retention: With reference to olmesartan medoxomil (retention time = about 10 min): impurity A = about 0.2; impurity B = about 0.7; impurity C = about 1.5.<\/p>\n
System suitability: Reference solution (a):<\/p>\n
\u2014 resolution: minimum 3.5 between the peaks due to impurity B and olmesartan medoxomil.<\/p>\n
Limits:<\/p>\n
\u2014 impurity A: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (0.4 per cent);<\/p>\n
\u2014 impurity C: not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.3 per cent);<\/p>\n
\u2014 unspecified impurities: for each impurity, not more than 0.5 times 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 3.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.7 per cent);<\/p>\n
\u2014 disregard limit: 0.25 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n
Acetone<\/h3>\n
Head-space gas chromatography (2.2.28): use the direct calibration method.<\/p>\n
Internal standard solution: Dilute 1.0 mL of butanol R to 100.0 mL with dimethyl sulfoxide R.<\/p>\n
Test solution: Dissolve 0.250 g of the substance to be examined in dimethyl sulfoxide R, add 2.0 mL of the internal standard solution and dilute to 10.0 mL with dimethyl sulfoxide R.<\/p>\n
Reference solution: Dilute 0.50 mL of acetone R to 200.0 mL with dimethyl sulfoxide R. Dilute 15.0 mL of the solution to 100.0 mL with dimethyl sulfoxide R. To 25.0 mL of this solution add 10.0 mL of the internal
\nstandard solution and dilute to 50.0 mL with dimethyl sulfoxide R.<\/p>\n
Column:<\/p>\n
\u2014 material: fused silica;<\/p>\n
\u2014 size: l = 30 m, \u00d8 = 0.53 mm;<\/p>\n
\u2014 stationary phase: macrogol 20 000 R (film thickness 1 \u03bcm).<\/p>\n
Carrier: gas nitrogen for chromatography R or helium for chromatography R.<\/p>\n
Flow rate: 4.0 mL\/min.<\/p>\n
Split ratio: 1:5.<\/p>\n
Static head-space conditions that may be used:<\/p>\n
\u2014 equilibration temperature: 80 \u00b0C;<\/p>\n
\u2014 equilibration time: 30 min.<\/p>\n
Temperature:<\/p>\n\n\n\n\n\n\n\n\n
<\/td>\n Time<\/strong>
\n(min)<\/strong><\/td>\n Temperature<\/strong>
\n(\u00b0C)<\/strong><\/td>\n<\/tr>\n
Column<\/td>\n 5<\/td>\n 50<\/td>\n<\/tr>\n
<\/td>\n 5 – 18<\/td>\n 50 \u2192 180<\/td>\n<\/tr>\n
<\/td>\n 18 – 23<\/td>\n 180<\/td>\n<\/tr>\n
Injection port<\/td>\n <\/td>\n 200<\/td>\n<\/tr>\n
Detection<\/td>\n <\/td>\n 200<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Detection: Flame ionisation.<\/p>\n
Injection: 1 mL.<\/p>\n
Calculate the content of acetone, taking its relative density to be 0.79 at 20 \u00b0C.<\/p>\n
Limit:<\/p>\n
\u2014 acetone: maximum 0.6 per cent.<\/p>\n
Water (2.5.32)<\/h3>\n
Maximum 0.5 per cent, determined on 0.500 g.<\/p>\n
Sulfated ash (2.4.14)<\/h3>\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 modifications.<\/p>\n
Mobile phase: Mobile phase B, mobile phase A (25:75 V\/V).<\/p>\n
Injection: Test solution (b) and reference solution (c).<\/p>\n
Retention time: Olmesartan medoxomil = about 10 min.<\/p>\n
Run time: 1.5 times the retention time of olmesartan medoxomil.<\/p>\n
Calculate the percentage content of C_{29<\/sub>H_{30<\/sub>N_{6<\/sub>O_{6 <\/sub>taking into account the assigned content of olmesartan medoxomil CRS.<\/p>\n}}}}
IMPURITIES<\/h2>\n
Specified impurities A, C.<\/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, D.<\/p>\n
$\"Olmesartan$ <\/p>\n
A. 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2\u2032-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylic acid (olmesartan),<\/p>\n
$\"Olmesartan$ <\/p>\n
B. 6,6-dimethyl-2-propyl-3-[[2\u2032-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-3,6-dihydro-4H-furo[3,4-d]imidazol-4-one,<\/p>\n
$\"Olmesartan$ <\/p>\n
C. (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(1-methylethenyl)-2-propyl-1-[[2\u2032-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylate,<\/p>\n
$\"Olmesartan$ <\/p>\n
D. (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2\u2032-[(2-triphenylmethyl)-2H-tetrazol-5-yl]biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylate.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 2600) C29H30N6O6 558.6 144689-63-4 Action and use Angiotensin II (AT1) receptor antagonist. Preparation Olmesartan Tablets DEFINITION (5-Methyl-2-oxo-1,3-dioxol-4-yl)methyl 4-(1-hydroxy-1-methylethyl)-2-propyl-1-[[2\u2032-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl]-1H-imidazole-5-carboxylate. Content 97.5 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility Practically insoluble in water, slightly soluble in ethanol (96 per cent), practically insoluble in heptane….<\/p>\n","protected":false},"author":4,"featured_media":26041,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26004","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\/26004","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=26004"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26004\/revisions"}],"predecessor-version":[{"id":26049,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26004\/revisions\/26049"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26041"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26004"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26004"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26004"}],"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 or almost white, crystalline powder.<\/p>\n

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

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

TESTS<\/h2>\n

Water (2.5.32)<\/h3>\nMaximum 0.5 per cent, determined on 0.500 g.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\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 or almost white, crystalline powder.<\/p>\n

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

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

Water (2.5.32)<\/h3>\n
Maximum 0.5 per cent, determined on 0.500 g.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n