{"id":27999,"date":"2025-11-07T16:18:15","date_gmt":"2025-11-07T09:18:15","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=27999"},"modified":"2025-11-07T16:18:15","modified_gmt":"2025-11-07T09:18:15","slug":"metoprolol-tartrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/metoprolol-tartrate\/","title":{"rendered":"Metoprolol Tartrate"},"content":{"rendered":"

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

(Ph. Eur. monograph 1028)<\/p>\n

\"Metoprolol<\/p>\n

C34<\/sub>H56<\/sub>N2<\/sub>O12<\/sub> 685 56392-17-7<\/p>\n

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

Beta-adrenoceptor antagonist.<\/p>\n

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

Metoprolol Injection<\/p>\n

Metoprolol Oral Suspension<\/p>\n

Metoprolol Tartrate Prolonged-release Tablets<\/p>\n

Metoprolol Tartrate Tablets<\/p>\n

Ph Eur<\/p>\n

DEFINITION<\/h2>\n

Bis[(2RS)-1-[4-(2-methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]propan-2-ol] (2R,3R)-2,3 dihydroxybutanedioate.<\/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 or colourless crystals.<\/p>\n

Solubility<\/h3>\n

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

It shows polymorphism (5.9).<\/p>\n

IDENTIFICATION<\/h2>\n

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

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

Comparison metoprolol tartrate CRS.<\/p>\n

If the spectra obtained in the solid state show differences, record further spectra using discs prepared by placing 25 \u03bcL of a 100 g\/L solution in methylene chloride R on a disc of potassium bromide R and evaporating the solvent. Examine immediately.<\/p>\n

TESTS<\/h3>\n

Solution S<\/h3>\n

Dissolve 0.500 g in carbon dioxide-free water R and dilute to 25.0 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n

Solution S is clear (2.2.1) and not more intensely coloured than reference solution B8<\/p>\n

(2.2.2, Method II).<\/p>\n

pH (2.2.3)<\/h3>\n

6.0 to 7.0 for solution S.<\/p>\n

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

+ 7.0 to + 10.0 (dried substance), determined on solution S.<\/p>\n

Impurities M, N, O<\/h3>\n

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

Test solution Dissolve 0.50 g of the substance to be examined in methanol R and dilute to 10 mL with the same solvent.<\/p>\n

Reference solution (a) Dilute 1 mL of the test solution to 20 mL with methanol R. Dilute 5 mL of this solution to 50 mL with methanol R.<\/p>\n

Reference solution (b) Dilute 4 mL of reference solution (a) to 10 mL with methanol R.<\/p>\n

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

Mobile phase Place 2 beakers, each containing 30 volumes of concentrated ammonia R, at the bottom of a chromatographic tank containing a mixture of 20 volumes of methanol R and 80 volumes of ethyl acetate R.<\/p>\n

Application 5 \u03bcL.<\/p>\n

Development Over 2\/3 of the plate in a tank saturated for at least 1 h.<\/p>\n

Drying In air for at least 3 h.<\/p>\n

Detection Expose the plate to iodine vapour for at least 15 h.<\/p>\n

Limits:<\/p>\n

– any impurity: any spot, apart from the principal spot, is not more intense than the spot in the chromatogram obtained with reference solution (a) (0.5 per cent) and at most 1 such spot is more intense than the spot in the chromatogram obtained with reference solution (b) (0.2 per cent);<\/p>\n

– disregard any spot on the line of application.<\/p>\n

Related substances<\/h3>\n

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

Test solution Dissolve 20.0 mg of the substance to be examined in the mobile phase and dilute to 10.0 mL with the mobile phase.<\/p>\n

Reference solution (a) Dissolve 1.5 mg of metoprolol impurity A CRS and 2.5 mg of metoprolol tartrate CRS in the mobile phase and dilute to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (b) Dilute 1.0 mL of the test solution to 20.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 50.0 mL with the mobile phase.<\/p>\n

Column:<\/p>\n

– size: l = 0.15 m, \u00d8 = 3.9 mm;<\/p>\n

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

Mobile phase Dissolve 3.9 g of ammonium acetate R in 810 mL of water R, add 2.0 mL of triethylamine R, 3.0 mL of phosphoric acid R, 10.0 mL of glacial acetic acid R and 146 mL of acetonitrile R and mix.<\/p>\n

Flow rate 1 mL\/min.<\/p>\n

Detection Spectrophotometer at 280 nm.<\/p>\n

Injection 20 \u03bcL.<\/p>\n

Run time 3 times the retention time of metoprolol.<\/p>\n

Relative retention With reference to metoprolol (retention time = about 7 min): impurity H = about 0.3; impurity C = about 0.4; impurity G = about 0.45; impurity F = about 0.7; impurity A = about 0.8; impurity J = about 1.4; impurity D = about 1.6; impurity E = about 1.8; impurity B = about 2.<\/p>\n

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

– resolution: minimum 6.0 between the peaks due to impurity A and metoprolol.<\/p>\n

Limits:<\/p>\n

– correction factor: for the calculation of content, multiply the peak area of impurity C by 0.1;<\/p>\n

– impurities A, B, C, D, E, F, G, H, J: for each impurity, 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

– 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

– total: not more than 5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.5 per cent);<\/p>\n

– disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent); disregard any peak due to tartaric acid.<\/p>\n

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

Maximum 0.5 per cent, determined on 1.000 g by drying in vacuo over anhydrous calcium chloride R for 4 h.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\n

Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Dissolve 0.250 g in 30 mL of anhydrous acetic acid R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).<\/p>\n

1 mL of 0.1 M perchloric acid is equivalent to 34.24 mg of C34H56N2O12.<\/p>\n

STORAGE<\/h2>\n

Protected from light.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, C, D, E, F, G, H, J, M, N, O.<\/p>\n

\"Metoprolol<\/p>\n

A. (2RS)-1-(ethylamino)-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol,<\/p>\n

\"Metoprolol<\/p>\n

B. 4-(2-methoxyethyl)phenol,<\/p>\n

\"Metoprolol<\/p>\n

C. 4-[(2RS)-2-hydroxy-3-[(1-methylethyl)amino]propoxy]benzaldehyde,<\/p>\n

\"Metoprolol<\/p>\n

D. (2RS)-3-[4-(2-methoxyethyl)phenoxy]propane-1,2-diol,<\/p>\n

\"Metoprolol<\/p>\n

E. (2RS)-1-[2-(2-methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]propan-2-ol,<\/p>\n

\"Metoprolol<\/p>\n

F. (2RS)-1-[(1-methylethyl)amino]-3-phenoxypropan-2-ol,<\/p>\n

\"Metoprolol<\/p>\n

G. 2-(4-hydroxyphenyl)ethanol,<\/p>\n

\"Metoprolol<\/p>\n

H. (2RS)-1-[4-(2-hydroxyethyl)phenoxy]-3-[(1-methylethyl)amino]propan-2-ol,<\/p>\n

\"Metoprolol<\/p>\n

J. mixture of the 4 stereoisomers of 1-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]-3-[4-(2-methoxyethyl)phenoxy]propan-2-ol,<\/p>\n

\"Metoprolol<\/p>\n

M. 1,3-bis[(1-methylethyl)amino]propan-2-ol,<\/p>\n

\"Metoprolol<\/p>\n

N. (2RS)-3-[(1-methylethyl)amino]propane-1,2-diol,<\/p>\n

\"Metoprolol<\/p>\n

O. mixture of the 3 stereoisomers of 1,1\u2032-[(1-methylethyl)imino]bis[3-[4-(2-methoxyethyl)phenoxy]propan-2-ol].<\/p>\n

Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":"

Edition: BP 2025 (Ph. Eur. 11.6 update) (Ph. Eur. monograph 1028) C34H56N2O12 685 56392-17-7 Action and use Beta-adrenoceptor antagonist. Preparations Metoprolol Injection Metoprolol Oral Suspension Metoprolol Tartrate Prolonged-release Tablets Metoprolol Tartrate Tablets Ph Eur DEFINITION Bis[(2RS)-1-[4-(2-methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]propan-2-ol] (2R,3R)-2,3 dihydroxybutanedioate. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline…<\/p>\n","protected":false},"author":5,"featured_media":28023,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-27999","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\/27999","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=27999"}],"version-history":[{"count":1,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/27999\/revisions"}],"predecessor-version":[{"id":28025,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/27999\/revisions\/28025"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/28023"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=27999"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=27999"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=27999"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}