{"id":31081,"date":"2025-11-12T17:14:24","date_gmt":"2025-11-12T10:14:24","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=31081"},"modified":"2025-11-12T18:06:04","modified_gmt":"2025-11-12T11:06:04","slug":"verapamil-hydrochloride","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/verapamil-hydrochloride\/","title":{"rendered":"Verapamil Hydrochloride"},"content":{"rendered":"

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

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

Calcium channel blocker.<\/p>\n

Preparations<\/strong><\/p>\n

Verapamil Prolonged-release Capsules<\/p>\n

Verapamil Prolonged-release Tablets Verapamil Injection<\/p>\n

Verapamil Oral Solution Verapamil Tablets<\/p>\n

DEFINITION<\/h2>\n

(2RS)-2-(3,4-Dimethoxyphenyl)-5-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]-2-(propan-2-yl)pentanenitrile hydrochloride.<\/p>\n

Content<\/strong><\/p>\n

99.0 per cent to 101.0 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Soluble in water, freely soluble in methanol, sparingly soluble in ethanol (96 per cent).<\/p>\n

IDENTIFICATION<\/h2>\n

First identification: B, D.<\/em><\/p>\n

Second identification: A, C, D.<\/em><\/p>\n

A. Ultraviolet and visible absorption spectrophotometry (2.2.25).<\/p>\n

Test solution Dissolve 20.0 mg in a 1.03 g\/L solution of hydrochloric acid R and dilute to 100.0 mL with the same acid. Dilute 5.0 mL of this solution to 50.0 mL with a 1.03 g\/L solution of hydrochloric acid R.<\/p>\n

Spectral range\u00a0 210-340 nm.<\/p>\n

Absorption maxima\u00a0 229 nm and 278 nm.<\/p>\n

Shoulder\u00a0 282 nm.<\/p>\n

Absorbance ratio\u00a0 A278\/A229 = 0.35 to 0.39.<\/p>\n

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

Comparison\u00a0 verapamil hydrochloride CRS.<\/p>\n

C. Thin-layer chromatography (2.2.27).<\/p>\n

Test solution Dissolve 10 mg of the substance to be examined in methylene chloride R and dilute to 5 mL with the same solvent.<\/p>\n

Reference solution (a) Dissolve 20 mg of verapamil hydrochloride CRS in methylene chloride R and dilute to 10 mL with the same solvent.<\/p>\n

Reference solution (b) Dissolve 5 mg of papaverine hydrochloride CRS in reference solution (a) and dilute to 5 mL with the same solution.<\/p>\n

Plate\u00a0 TLC silica gel F254 plate R.<\/p>\n

Mobile phase diethylamine R, cyclohexane R (15:85 V\/V). Application 5 \u00b5L.<\/p>\n

Development\u00a0 Over 3\/4 of the plate.<\/p>\n

Drying\u00a0 In air.<\/p>\n

Detection\u00a0 Examine in ultraviolet light at 254 nm.<\/p>\n

System suitability\u00a0 Reference solution (b):<\/p>\n

\u2014 the chromatogram shows 2 clearly separated principal spots.<\/p>\n

Results The principal spot in the chromatogram obtained with the test solution is similar in position and size to the principal spot in the chromatogram obtained with reference solution (a).<\/p>\n

D. Dissolve about 28 mg in 2 mL of methanol R. The solution gives reaction (a) of chlorides (2.3.1); use methanol R instead of water R to wash the precipitate.<\/p>\n

TESTS<\/h2>\n

Solution S<\/h3>\n

Dissolve 1.0 g in carbon dioxide-free water R with gentle heating and dilute to 20.0 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n

Solution S is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n

pH (2.2.3)<\/strong><\/p>\n

4.5 to 6.0 for solution S.<\/p>\n

Optical rotation (2.2.7)<\/strong><\/p>\n

-0.10\u00b0 to + 0.10\u00b0, determined on solution S.<\/p>\n

Related substances<\/h3>\n

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

Solvent mixture\u00a0 Mobile phase B, mobile phase A (37:63 V\/V).<\/p>\n

Test solution Dissolve 25.0 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n

Reference solution (a)\u00a0 Dissolve 5 mg of verapamil hydrochloride CRS, 5 mg of verapamil impurity I CRS and 5 mg of verapamil impurity M CRS in the solvent mixture and dilute to 20 mL with the solvent mixture. Dilute 1 mL of this solution to 10 mL with the solvent mixture.<\/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

Column:<\/p>\n

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

\u2014 stationary phase: end-capped polar-embedded octadecylsilyl amorphous organosilica polymer R (5 \u00b5m).<\/p>\n

Mobile phase:<\/p>\n

\u2014 mobile phase A: 6.97 g\/L solution of dipotassium hydrogen phosphate R adjusted to pH 7.20 with phosphoric acid R;<\/p>\n

\u2014 mobile phase B: acetonitrile R;<\/p>\n\n\n\n\n\n\n
Time (min)<\/strong><\/td>\nMobile phase A (per cent V\/V)<\/strong><\/td>\nMobile phase B (per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 22<\/td>\n63<\/td>\n37<\/td>\n<\/tr>\n
22 – 27<\/td>\n63 \u2192 35<\/td>\n37 \u2192 65<\/td>\n<\/tr>\n
27 – 45<\/td>\n35<\/td>\n65<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate\u00a0 1.5 mL\/min.<\/p>\n

Detection\u00a0 Spectrophotometer at 278 nm.<\/p>\n

Injection\u00a0 10 \u00b5L.<\/p>\n

Relative retention With reference to verapamil (retention time = about 15 min): impurity I = about 1.3; impurity M = about 2.4.<\/p>\n

System suitability\u00a0 Reference solution (a):<\/p>\n

\u2014 resolution: minimum 4.5 between the peaks due to verapamil and impurity I;<\/p>\n

\u2014 impurity M elutes from the column.<\/p>\n

Limits:<\/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)<\/strong><\/p>\n

Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/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

Dissolve 0.400 g in 50 mL of anhydrous ethanol R and add 5.0 mL of 0.01 M hydrochloric acid. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20). Measure the volume added between the 2 points of inflexion.<\/p>\n

1 mL of 0.1 M sodium hydroxide is equivalent to 49.11 mg of C27<\/sub>H39<\/sub>ClN2<\/sub>O4<\/sub>.<\/p>\n

STORAGE<\/h2>\n

Protected from light.<\/p>\n

IMPURITIES<\/h2>\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)\u00a0 A, B, C, D, E, F, G, H, I, J, K, L, M, N, O, P.<\/em><\/p>\n

\"Verapamil<\/p>\n

A. N1,N3-bis[2-(3,4-dimethoxyphenyl)ethyl]-N1,N3-dimethylpropane-1,3-diamine,<\/p>\n

\"Verapamil<\/p>\n

B. 2-(3,4-dimethoxyphenyl)-N-methylethan-1-amine,<\/p>\n

\"Verapamil<\/p>\n

C. 2-(3,4-dimethoxyphenyl)-N,N-dimethylethan-1-amine,<\/p>\n

\"Verapamil<\/p>\n

D. 3-chloro-N-[2-(3,4-dimethoxyphenyl)ethyl]-N-methylpropan-1-amine,<\/p>\n

\"Verapamil<\/p>\n

E. (3,4-dimethoxyphenyl)methanol,<\/p>\n

\"Verapamil<\/p>\n

F. (2RS)-2-(3,4-dimethoxyphenyl)-5-(methylamino)-2-(propan-2-yl)pentanenitrile,<\/p>\n

\"Verapamil<\/p>\n

G. 3,4-dimethoxybenzaldehyde,<\/p>\n

\"Verapamil<\/p>\n

H. (2RS)-2-(3,4-dimethoxyphenyl)-5-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]-2-ethylpentanenitrile,<\/p>\n

\"Verapamil<\/p>\n

I. (2RS)-2-(3,4-dimethoxyphenyl)-4-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]-2-(propan-2-yl)butanenitrile,<\/p>\n

\"Verapamil<\/p>\n

J. (2RS)-2-(3,4-dimethoxyphenyl)-5-[[2-(3,4-dimethoxy-phenyl)ethyl]amino]-2-(propan-2-yl)pentanenitrile (norverapamil),<\/p>\n

\"Verapamil<\/p>\n

K. (2RS)-2-(3,4-dimethoxyphenyl)-3-methylbutanenitrile,<\/p>\n

\"Verapamil<\/p>\n

L. 1-(3,4-dimethoxyphenyl)-2-methylpropan-1-one,<\/p>\n

\"Verapamil<\/p>\n

M. 5,5\u2032-[[2-(3,4-dimethoxyphenyl)ethyl]azanediyl]bis[(2\u039e)-2-(3,4-dimethoxyphenyl)-2-(propan-2-yl)pentanenitrile],<\/p>\n

\"Verapamil<\/p>\n

N. 5,5\u2032-(methylazanediyl)bis[(2\u039e)-2-(3,4-dimethoxyphenyl)-2-(propan-2-yl)pentanenitrile],<\/p>\n

\"Verapamil<\/p>\n

O. (2RS)-2-(3,4-dimethoxyphenyl)-5-[[2-(3,4-dimethoxy-phenyl)ethyl](methyl)amino]-2-propylpentanenitrile,<\/p>\n

\"Verapamil<\/p>\n

P. (2\u039e,6\u039e)-2,6-bis(3,4-dimethoxyphenyl)-2,6-di(propan-2-yl)heptane-1,7-dinitrile.<\/p>\n","protected":false},"excerpt":{"rendered":"

Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Calcium channel blocker. Preparations Verapamil Prolonged-release Capsules Verapamil Prolonged-release Tablets Verapamil Injection Verapamil Oral Solution Verapamil Tablets DEFINITION (2RS)-2-(3,4-Dimethoxyphenyl)-5-[[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino]-2-(propan-2-yl)pentanenitrile hydrochloride. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility Soluble in water, freely soluble in…<\/p>\n","protected":false},"author":5,"featured_media":31082,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-31081","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\/31081","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=31081"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31081\/revisions"}],"predecessor-version":[{"id":31202,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31081\/revisions\/31202"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/31082"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=31081"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=31081"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=31081"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}