{"id":29572,"date":"2025-11-10T17:41:00","date_gmt":"2025-11-10T10:41:00","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=29572"},"modified":"2025-11-11T16:31:09","modified_gmt":"2025-11-11T09:31:09","slug":"teriflunomide","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/teriflunomide\/","title":{"rendered":"Teriflunomide"},"content":{"rendered":"

(Ph. Eur. monograph 3036)<\/p>\n

C12<\/sub>H9<\/sub>F3<\/sub>N2<\/sub>O2<\/sub> 270.2 163451-81-8<\/p>\n

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

Immunomodulator; treatment of multiple sclerosis.<\/p>\n

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

Teriflunomide Tablets<\/p>\n

DEFINITION<\/h2>\n

(2Z)-2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]but-2-enamide.<\/p>\n

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

98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Practically insoluble in water, slightly soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\n

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

Comparison\u00a0\u00a0<\/em> teriflunomide CRS.<\/p>\n

TESTS<\/h2>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29). Use freshly prepared solutions.<\/p>\n

Buffer solution<\/em> 3.85 g\/L solution of ammonium acetate R in water for chromatography R adjusted to pH 5.5 with glacial acetic acid R.<\/p>\n

Solvent mixture<\/em> Buffer solution, acetonitrile R (20:80 V\/V).<\/p>\n

Test solution<\/em> Dissolve 20.0 mg of the substance to be examined in 40 mL of the solvent mixture and dilute to 100.0 mL with the solvent mixture.<\/p>\n

Reference solution (a)<\/em> 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

Reference solution (b)<\/em> Dissolve 10 mg of leflunomide impurity A CRS (teriflunomide impurity A) in acetonitrile R and dilute to 250 mL with the same solvent. Dilute 1 mL of the solution to 200 mL with the solvent mixture.<\/p>\n

Reference solution (c)<\/em> Dissolve 5 mg of teriflunomide impurity B CRS in acetonitrile R and dilute to 100 mL with the same solvent. Dilute 2 mL of the solution to 50 mL with the solvent mixture. To 1 mL of this solution add 1 mL of reference solution (b) and dilute to 10 mL with the solvent mixture.<\/p>\n

Reference solution (d)<\/em> Dissolve 20.0 mg of teriflunomide for assay CRS in 40 mL of the solvent mixture and dilute to 100.0 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: end-capped solid core octadecylsilyl silica gel for chromatography R (2.7 \u03bcm);<\/p>\n

\u2014 temperature: 40 \u00b0C.<\/p>\n

Mobile phase:<\/p>\n

\u2014 mobile phase A: acetonitrile for chromatography R, buffer solution (10:90 V\/V);<\/p>\n

\u2014 mobile phase B: buffer solution, acetonitrile for chromatography R (10:90 V\/V);<\/p>\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 – 2<\/td>\n76<\/td>\n24<\/td>\n<\/tr>\n
2 – 12<\/td>\n76 \u2192 23<\/td>\n24 \u2192 77<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate<\/em> 1.0 mL\/min.<\/p>\n

Detection<\/em> Spectrophotometer at 249 nm.<\/p>\n

Injection<\/em> 5 \u03bcL of the test solution and reference solutions (a) and (c).<\/p>\n

Identification of impurities<\/em> Use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A and B.<\/p>\n

Relative retention<\/em> With reference to teriflunomide (retention time = about 5 min): impurity B = about 1.5; impurity A = about 1.6.<\/p>\n

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

\u2014 resolution: minimum 1.5 between the peaks due to impurities B and A;<\/p>\n

\u2014 signal-to-noise ratio: minimum 10 for the peak due to impurity A.<\/p>\n

Calculation of percentage contents:<\/p>\n

\u2014 for each impurity, use the concentration of teriflunomide in reference solution (a).<\/p>\n

Limits:<\/p>\n

\u2014 impurity A: maximum 0.01 per cent;<\/p>\n

\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n

\u2014 total: maximum 0.2 per cent;<\/p>\n

\u2014 reporting threshold: 0.05 per cent; do not disregard the peak due to impurity A.<\/p>\n

Water (2.5.32)<\/h3>\n

Maximum 0.5 per cent, determined on 0.100 g by direct sample introduction.<\/p>\n

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

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

ASSAY<\/h2>\n

Liquid<\/em> chromatography (2.2.29) as described in the test for related substances with the following modifications.<\/p>\n

Injection<\/em> Test solution and reference solution (d).<\/p>\n

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

\u2014 symmetry factor: maximum 2.0 for the peak due to teriflunomide;<\/p>\n

\u2014 repeatability: maximum relative standard deviation of 1.2 per cent determined on 6 injections.<\/p>\n

Calculate the percentage content of C12<\/sub>H9<\/sub>F3<\/sub>N2<\/sub>O2 <\/sub>taking into account the assigned content of teriflunomide for assay CRS.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A.<\/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) B.<\/p>\n

\"Teriflunomide\"
\nA. 4-(trifluoromethyl)aniline (leflunomide impurity A),<\/p>\n

\"Teriflunomide\"
\nB. 2-cyano-N-[4-(trifluoromethyl)phenyl]acetamide.<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 3036) C12H9F3N2O2 270.2 163451-81-8 Action and use Immunomodulator; treatment of multiple sclerosis. Preparation Teriflunomide Tablets DEFINITION (2Z)-2-Cyano-3-hydroxy-N-[4-(trifluoromethyl)phenyl]but-2-enamide. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white powder. Solubility Practically insoluble in water, slightly soluble in anhydrous ethanol, practically insoluble in heptane. IDENTIFICATION Infrared absorption spectrophotometry…<\/p>\n","protected":false},"author":5,"featured_media":29621,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-29572","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\/29572","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=29572"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29572\/revisions"}],"predecessor-version":[{"id":29626,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29572\/revisions\/29626"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/29621"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=29572"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=29572"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=29572"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}