Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Antifungal.<\/p>\n (2R,3S)-2-(2,4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol.<\/p>\n Content<\/strong><\/p>\n 97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n White or almost white powder.<\/p>\n Very slightly soluble in water, freely soluble in acetone and in methylene chloride.<\/p>\n A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 voriconazole CRS.<\/p>\n B. Enantiomeric purity (see Tests).<\/p>\n The solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n Dissolve 0.5 g in a 103 g\/L solution of hydrochloric acid R and dilute to 20 mL with the same solution.<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution Dissolve 25.0 mg of the substance to be examined in 2 mL of acetonitrile R and dilute to 50.0 mL with the mobile phase.<\/p>\n Reference solution (a) Dissolve 5.0 mg of voriconazole impurity D CRS in 2 mL of acetonitrile R and dilute to 50.0 mL with the mobile phase.<\/p>\n Reference solution (b) Dissolve 25 mg of the substance to be examined in 2 mL of acetonitrile R, add 1 mL of reference solution (a) and dilute to 50.0 mL with the mobile phase.<\/p>\n Reference solution (c)\u00a0 Dilute 1.0 mL of reference solution (a) to 100.0 mL with the mobile phase.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: silica gel BC for chiral chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 30 \u00b0C.<\/p>\n Mobile phase Mix 18 volumes of acetonitrile R and 82 volumes of a 0.77 g\/L solution of ammonium acetate R previously adjusted to pH 5.0 with glacial acetic acid R.<\/p>\n Flow rate\u00a0 1.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 256 nm.<\/p>\n Injection\u00a0 20 \u00b5L of the test solution and reference solutions (b) and (c).<\/p>\n Run time\u00a0 2.5 times the retention time of voriconazole.<\/p>\n Relative retention\u00a0 With reference to voriconazole (retention time = about 7 min): impurity D = about 1.5.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 4.0 between the peaks due to voriconazole and impurity D.<\/p>\n Limit:<\/p>\n \u2014 impurity D: not more than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.2 per cent).<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution Dissolve 50.0 mg of the substance to be examined in 5.0 mL of methanol R and dilute to 10.0 mL with the mobile phase.<\/p>\n Reference solution (a) Dissolve 25.0 mg of voriconazole impurity E CRS in 50 mL of methanol R and dilute to 100.0 mL with the mobile phase.<\/p>\n Reference solution (b)\u00a0 Dissolve 17 mg of sodium chloride R in water R and dilute to 200.0 mL with the same solvent. Mix 1 mL of the solution, 1 mL of reference solution (a) and 25 mL of methanol R and dilute to 50.0 mL with the mobile phase.<\/p>\n Reference solution (c) To 1.0 mL of reference solution (a) add 25 mL of methanol R and dilute to 50.0 mL with the mobile phase.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.0 mm;<\/p>\n \u2014 stationary phase: strong ly basic anion-exchange resin for chromatography R (8.5 \u00b5m);<\/p>\n \u2014 temperature: 40 \u00b0C.<\/p>\n Mobile phase To 1500 mL of water R add 500 mL of methanol R, mix and degas; add about 175 \u00b5L of a 470 g\/L solution of sodium hydroxide R and mix.<\/p>\n Flow rate\u00a0 1.0 mL\/min.<\/p>\n Detection\u00a0 Conductivity detector; use a self-regenerating anion suppressor.<\/p>\n Injection\u00a0 20 \u00b5L of the test solution and reference solutions (b) and (c).<\/p>\n Run time\u00a0 Twice the retention time of impurity E.<\/p>\n Relative retention\u00a0 With reference to impurity E (retention time = about 4 min): chloride = about 1.5.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 3.5 between the peaks due to impurity E and chloride.<\/p>\n Limit:<\/p>\n \u2014 impurity E: not more than the area of the principal peak in the chromatogram obtained with reference solution (c) (0.10 per cent).<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution (a) Dissolve 50.0 mg of the substance to be examined in the mobile phase, sonicating if necessary, and dilute to 100.0 mL with the mobile phase. Mix well to ensure complete dissolution.<\/p>\n Test solution (b)\u00a0 Dilute 5.0 mL of test solution (a) to 100.0 mL with the mobile phase.<\/p>\n Reference solution (a)\u00a0 Dissolve 50.0 mg of voriconazole CRS in the mobile phase, sonicating if necessary, and dilute to 100.0 mL with the mobile phase. Mix well to ensure complete dissolution. Dilute 5.0 mL of the solution to 100.0 mL with the mobile phase.<\/p>\n Reference solution (b) Suspend 0.100 g of the substance to be examined in 10 mL of a 40 g\/L solution of sodium hydroxide R and dilute to 20 mL with the mobile phase; sonicate if necessary. Allow to stand for 30 min. Dilute 1.0 mL of the solution to 100.0 mL with the mobile phase (in situ degradation to obtain impurities A and C).<\/p>\n Reference solution (c) Dilute 1.0 mL of test solution (a) to 100.0 mL with the mobile phase and mix. Dilute 1.0 mL of this solution to 10.0 mL with the mobile phase and mix well.<\/p>\n Reference solution (d) Dissolve 2 mg of voriconazole impurity B CRS in the mobile phase and dilute to 200 mL with the mobile phase. Dilute 1.0 mL of the solution to 10.0 mL with the mobile phase.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.15 m, \u00d8 = 3.9 mm;<\/p>\n \u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (4 \u00b5m);<\/p>\n \u2014 temperature: 35 \u00b0C.<\/p>\n Mobile phase\u00a0 Mix 15 volumes of acetonitrile R, 30 volumes of methanol R and 55 volumes of a 1.90 g\/L solution of ammonium formate R previously adjusted to pH 4.0 with formic acid R while stirring continuously.<\/p>\n Flow rate\u00a0 1.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 256 nm.<\/p>\n Injection\u00a0 20 \u00b5L of test solution (a) and reference solutions (b), (c) and (d).<\/p>\n Run time\u00a0 3 times the retention time of voriconazole.<\/p>\n Identification of impurities Use the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A and C; use the chromatogram obtained with reference solution (d) to identify the peak due to impurity B.<\/p>\n Relative retention With reference to voriconazole (retention time = about 8 min): impurity A = about 0.25; impurity C = about 0.3; impurity B = about 0.6.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 1.8 between the peaks due to impurities A 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 A = 0.7; impurity B = 2.1; impurity C = 0.7;<\/p>\n \u2014 impurities A, B, C: for each impurity, not more than 1.5 times the area of the principal peak in the chromatogram obtained with reference solution (c) (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 (c) (0.10 per cent);<\/p>\n \u2014 sum of impurities A, B, C, D, E and unspecified impurities: maximum 0.5 per cent;<\/p>\n \u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (c) (0.05 per cent).<\/p>\n Water (2.5.12)<\/strong><\/p>\n Maximum 0.4 per cent, determined on 1.00 g.<\/p>\n Sulfated ash (2.4.14)<\/strong><\/p>\n Maximum 0.1 per cent, determined on 1.0 g in a platinum crucible.<\/p>\n Bacterial endotoxins (2.6.14)<\/strong><\/p>\n Less than 0.2 IU\/mg, if intended for use in the manufacture of parenteral preparations without a further appropriate procedure for the removal of bacterial endotoxins.<\/p>\n ASSAY<\/p>\n Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n Injection\u00a0 Test solution (b) and reference solution (a).<\/p>\n Calculate the percentage content of C16<\/sub>H14<\/sub>F3<\/sub>N5<\/sub>O taking into account the assigned content of voriconazole CRS.<\/p>\n If the substance is sterile, store in a sterile, airtight, tamper-evident container.<\/p>\n Specified impurities\u00a0 A, B, C, D, E.<\/em><\/p>\n A. 1-(2,4-difluorophenyl)-2-(1H-1,2,4-triazol-1-yl)ethanone,<\/p>\n B. (2RS,3SR)-2-(2,4-difluorophenyl)-3-pyrimidin-4-yl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol,<\/p>\n C. 4-ethyl-5-fluoropyrimidine,<\/p>\n D. (2S,3R)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol (voriconazole enantiomer),<\/p>\n E. [(1R,4S)-7,7-dimethyl-2-oxobicyclo[2.2.1]hept-1-yl]methanesulfonic acid ((\u00b1)-10-camphorsulfonic acid).<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Antifungal. DEFINITION (2R,3S)-2-(2,4-Difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol. Content 97.5 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white powder. Solubility Very slightly soluble in water, freely soluble in acetone and in methylene chloride. IDENTIFICATION A. Infrared absorption spectrophotometry (2.2.24). Comparison\u00a0 voriconazole CRS. B. Enantiomeric…<\/p>\n","protected":false},"author":5,"featured_media":31493,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-31492","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\/31492","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=31492"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31492\/revisions"}],"predecessor-version":[{"id":31503,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31492\/revisions\/31503"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/31493"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=31492"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=31492"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=31492"}],"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
Enantiomeric purity<\/h3>\n
Impurity E<\/h3>\n
Related substances<\/h3>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n