Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Vitamin K epoxide reductase inhibitor; oral anticoagulant (coumarin).<\/p>\n Preparations<\/strong><\/p>\n Warfarin Oral Suspension<\/p>\n Warfarin Tablets<\/p>\n Sodium 2-oxo-3-[(1RS)-3-oxo-1-phenylbutyl]-2H-1-benzopyran-4-olate.<\/p>\n Content<\/strong><\/p>\n 98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n White or almost white, hygroscopic, amorphous powder.<\/p>\n Very soluble in water and in ethanol (96 per cent), soluble in acetone, very slightly soluble in methylene chloride.<\/p>\n A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 warfarin sodium CRS.<\/p>\n B. Propan-2-ol (see Tests).<\/p>\n C. It gives reaction (b) of sodium (2.3.1).<\/p>\n The solution is clear (2.2.1) and colourless (2.2.2, Method II). Dissolve 1.0 g in water R and dilute to 20 mL with the same solvent.<\/p>\n pH (2.2.3)<\/strong><\/p>\n 7.6 to 8.6.<\/p>\n Dissolve 1.0 g in carbon dioxide-free water R and dilute to 100 mL with the same solvent.<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Solvent mixture\u00a0 methanol R, water R (25:75 V\/V).<\/p>\n Test solution Dissolve 40.0 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) Dissolve 2 mg of 4-hydroxycoumarin R (impurity B) and 2 mg of benzalacetone R (impurity C) in 25 mL of methanol R and dilute to 100 mL with water R.<\/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 = 4.0 mm;<\/p>\n \u2014 stationary phase: cyanosilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 30 \u00b0C.<\/p>\n Mobile phase glacial acetic acid R, acetonitrile R, water R (1:25:75 V\/V\/V). Flow rate 1.5 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 260 nm.<\/p>\n Injection\u00a0 20 \u00b5L.<\/p>\n Run time\u00a0 Twice the retention time of warfarin.<\/p>\n Identification of impurities Use the chromatogram obtained with reference solution (a) to identify the peaks due to impurities B and C.<\/p>\n Relative retention With reference to warfarin (retention time = about 9 min): impurity B = about 0.4; impurity C = about 0.6.<\/p>\n System suitability\u00a0 Reference solution (a):<\/p>\n \u2014 resolution: minimum 2.0 between the peaks due to impurities B and C.<\/p>\n Limits:<\/p>\n \u2014 correction factors: for the calculation of content, multiply the peak areas of the following impurities by the corresponding correction factor: impurity B = 0.5; impurity C = 0.4;<\/p>\n \u2014 impurities B, C: for each impurity, 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 Dissolve 1.25 g in a 20 g\/L solution of sodium hydroxide R and dilute to 10.0 mL with the same solvent. The absorbance (2.2.25) is maximum 0.20 measured at 385 nm within 15 min of preparing the solution.<\/p>\n Propan-2-ol (2.4.24, System A) Maximum 0.5 per cent.<\/p>\n Water (2.5.12)<\/strong><\/p>\n Maximum 4.0 per cent, determined on 0.750 g.<\/p>\n Dissolve 0.100 g in 0.01 M sodium hydroxide and dilute to 100.0 mL with the same solvent. Dilute 10.0 mL of the solution to 100.0 mL with 0.01 M sodium hydroxide.<\/p>\n Dilute 10.0 mL of this solution to 100.0 mL with 0.01 M sodium hydroxide.<\/p>\n Measure the absorbance (2.2.25) at the absorption maximum at 308 nm.<\/p>\n Calculate the percentage content of C19<\/sub>H15<\/sub>NaO4<\/sub> taking the specific absorbance to be 431.<\/p>\n In an airtight container, protected from light.<\/p>\n Specified impurities\u00a0 B, C.<\/em><\/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) A.<\/em><\/p>\n A. (5RS)-3-(2-hydroxyphenyl)-5-phenylcyclohex-2-enone,<\/p>\n B. 4-hydroxy-2H-1-benzopyran-2-one (4-hydroxycoumarin),<\/p>\n C. (3E)-4-phenylbut-3-en-2-one (benzalacetone).<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Vitamin K epoxide reductase inhibitor; oral anticoagulant (coumarin). Preparations Warfarin Oral Suspension Warfarin Tablets DEFINITION Sodium 2-oxo-3-[(1RS)-3-oxo-1-phenylbutyl]-2H-1-benzopyran-4-olate. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, hygroscopic, amorphous powder. Solubility Very soluble in water and in ethanol (96…<\/p>\n","protected":false},"author":5,"featured_media":31506,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-31504","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\/31504","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=31504"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31504\/revisions"}],"predecessor-version":[{"id":31510,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31504\/revisions\/31510"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/31506"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=31504"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=31504"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=31504"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
Related substances<\/h3>\n
Phenolic ketones<\/h3>\n
ASSAY<\/h2>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n