{"id":6534,"date":"2025-09-30T16:29:34","date_gmt":"2025-09-30T09:29:34","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=6534"},"modified":"2025-10-02T15:14:57","modified_gmt":"2025-10-02T08:14:57","slug":"cabazitaxel-acetone-concentrate-for-infusion","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/cabazitaxel-acetone-concentrate-for-infusion\/","title":{"rendered":"Cabazitaxel acetone concentrate for infusion"},"content":{"rendered":"

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

General Notices<\/div>\n

(Ph. Eur. monograph 3061)<\/div>\n

Ph Eur<\/div>\n

DEFINITION<\/h2>\n
Sterile concentrate for solution for infusion of Cabazitaxel acetone (3060), for human use.<\/div>\n
It complies with the monograph Parenteral preparations (0520) and the following additional requirements.<\/div>\n
Content<\/h3>\n
95.0 per cent to 105.0 per cent of the content of cabazitaxel (C_{45<\/sub>H_{57<\/sub>NO_{14<\/sub>) stated on the label.<\/div>\nPRODUCTION<\/h2>\nManufacturers are expected to evaluate whether the presence of the active substance as a solvate is critical to the quality,<\/p>\n
efficacy and\/or safety of the medicinal product and, where applicable, implement a control strategy for the corresponding<\/div>\nsolvent in the medicinal product, to the satisfaction of the competent authorities.<\/div>\nIDENTIFICATION<\/h2>\nCarry out either tests A, B or tests B, C.<\/div>\nA. Record the UV spectrum of the principal peak in the chromatograms obtained with the solutions used in the assay, with a diode array detector in the range of 190-400 nm.<\/div>\nResults The UV spectrum of the principal peak in the chromatogram obtained with the test solution is similar to the<\/div>\nUV spectrum of the principal peak in the chromatogram obtained with reference solution (b).<\/div>\nB. Examine the chromatograms obtained in the assay.<\/div>\nResults The principal peak in the chromatogram obtained with the test solution is similar in retention time and size to the principal peak in the chromatogram obtained with reference solution (b).<\/div>\nC. Thin-layer chromatography (2.2.27).<\/div>\nTest solution Dilute a suitable volume of the preparation to be examined with methylene chloride R to obtain a concentration of cabazitaxel of 0.4 mg\/mL.<\/div>\nReference solution Dissolve 4 mg of cabazitaxel acetone CRS in 10 mL of a mixture of polysorbate 80 R and methylene chloride R (1:99 V\/V).<\/div>\nPlate TLC silica gel F254 plate R.<\/div>\nMobile phase methanol R, methylene chloride R (8:92 V\/V).<\/div>\nCabazitaxel acetone concentrate for infusion<\/div>\nApplication 10 \u03bcL.<\/div>\nDevelopment Over 1\/2 of the plate.<\/div>\nDetection Examine in ultraviolet light at 254 nm.<\/div>\nResults 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 the reference solution.<\/div>\nTESTS<\/h2>\npH (2.2.3)<\/div>\n3.0 to 4.0.<\/div>\nPrepare a 10 per cent m\/m solution of the preparation to be examined in carbon dioxide-free water R.<\/div>\nRelated substances<\/div>\nLiquid chromatography (2.2.29).<\/div>\nSolvent mixture acetonitrile R, methanol R, water R previously adjusted to pH 4.0 with dilute phosphoric acid R1 (26:32:42 V\/V\/V).<\/div>\nTest solution To a quantity of the preparation to be examined containing the equivalent of 20.0 mg of cabazitaxel, add 5 mL of anhydrous ethanol R and dilute to 100.0 mL with the solvent mixture.<\/div>\nReference solution (a) Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 2.0 mL of this solution to 10.0 mL with the solvent mixture.<\/div>\nReference solution (b) Dissolve 20.0 mg of cabazitaxel acetone CRS in 5 mL of anhydrous ethanol R and dilute to 100.0 mL with the solvent mixture.<\/div>\nReference solution (c) Dissolve 4 mg of cabazitaxel for peak identification CRS (containing impurities C, D, E, F and G) in 1 mL anhydrous ethanol R and dilute to 20 mL with the solvent mixture.<\/div>\nReference solution (d) Dissolve 4 mg of cabazitaxel for system suitability CRS (containing impurity A) in 1 mL anhydrous ethanol R and dilute to 20 mL with the solvent mixture.<\/div>\nReference solution (e) To 4 mg of cabazitaxel impurity FP-A CRS, add 5 mL of anhydrous ethanol R and 20 mL of the solvent mixture. Dissolve using sonication. Dilute 1 mL of the solution to 25 mL with the solvent mixture. Dilute 1 mL of this solution to 10 mL with the solvent mixture.<\/div>\nColumn:<\/div>\n\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/div>\n\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 \u03bcm);<\/div>\n\u2014 temperature: 30 \u00b0C.<\/div>\nMobile phase:<\/div>\n\u2014 mobile phase A: methanol R1, acetonitrile for chromatography R, water for chromatography R previously adjusted to pH 4.0 with dilute phosphoric acid R1 (25:35:40 V\/V\/V);<\/div>\n\u2014 mobile phase B: methanol R1, water for chromatography R previously adjusted to pH 4.0 with dilute phosphoric acid R1, acetonitrile for chromatography R (25:25:50 V\/V\/V);<\/div>\n\u2014 mobile phase C: anhydrous ethanol R, acetonitrile for chromatography R (20:80 V\/V);<\/div>\n\n\n\n\n\n\n\n\n\n\nTime<\/div>\n(min)<\/div>\n<\/td>\n \nMobile phase A<\/div>\n(per cent V\/V)<\/div>\n<\/td>\n \nMobile phase B<\/div>\n(per cent V\/V)<\/div>\n<\/td>\n \nMobile phase C<\/div>\n(per cent V\/V)<\/div>\n<\/td>\n<\/tr>\n
0 – 2<\/td>\n 100<\/td>\n 0<\/td>\n 0<\/td>\n<\/tr>\n
2 – 22<\/td>\n 100 \u2192 0<\/td>\n 0 \u2192 100<\/td>\n 0<\/td>\n<\/tr>\n
22 – 44<\/td>\n 0<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
44 – 44.1<\/td>\n 0<\/td>\n 100 \u2192 0<\/td>\n 0 \u2192 100<\/td>\n<\/tr>\n
44.1 – 50<\/td>\n 0<\/td>\n 0<\/td>\n 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\nFlow rate 0.9 mL\/min.<\/div>\nDetection Spectrophotometer at 230 nm.<\/div>\nAutosampler Set at 10 \u00b0C.<\/div>\nInjection 25 \u03bcL of the test solution and reference solutions (a), (c), (d) and (e). Identification of impurities Use the chromatogram supplied with cabazitaxel for peak identification CRS and the chromatogram obtained with reference solution (c) to identify the peaks due to impurities C, D + F, E and G; use the chromatogram supplied with cabazitaxel for system suitability CRS and the chromatogram obtained with reference solution (d) to identify the peak due to impurity A; use the chromatogram obtained with reference solution (e) to identify the peak due to impurity FP-A.<\/div>\nRelative retention With reference to cabazitaxel (retention time = about 19 min): impurity FP-A = about 0.4;<\/div>\nimpurity A = about 0.96; impurity C = about 1.4; impurities D + F = about 1.61; impurity E = about 1.65;<\/div>\nimpurity G = about 1.74.<\/div>\nSystem suitability Reference solution (d):<\/div>\n\u2014 resolution : minimum 1.5 between the peaks due to impurity A and cabazitaxel.<\/div>\nCalculation of percentage contents:<\/div>\n\u2014 correction factor: multiply the peak area of impurity FP-A by 0.7;<\/div>\n\u2014 for each impurity, use the concentration of cabazitaxel in reference solution (a).<\/div>\nLimits:<\/div>\n\u2014 impurity FP-A: maximum 0.30 per cent;<\/div>\n\u2014 unspecified impurities: for each impurity, maximum 0.20 per cent;<\/div>\n\u2014 total: maximum 0.80 per cent;<\/div>\n\u2014 reporting threshold: 0.10 per cent; disregard the peaks due to impurities A, C, D + F, E and G.<\/div>\nASSAY<\/h2>\nLiquid chromatography (2.2.29) as described in the test for related substances with the following modifications.<\/div>\nInjection Test solution and reference solution (b).<\/div>\nSystem suitability Reference solution (b):<\/div>\n\u2014 repeatability: maximum relative standard deviation of 1.0 per cent determined on 6 injections.<\/div>\nCalculate the percentage content of cabazitaxel (C45H57NO14), taking into account the assigned content of cabazitaxel acetone CRS.<\/div>\nIMPURITIES<\/h2>\nSpecified impurities FP-A.<\/div>\n<\/div>\nOther detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph): A, B, C, D, E, F, G, H.<\/div>\n\n<\/p>\n<\/div>\n
A. 4-(acetyloxy)-13\u03b1-[[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-7\u03b2,10\u03b2-dimethoxy-9-oxo-5\u03b2,20-epoxytax-11-en-2\u03b1-yl (2E)-2-methylbut-2-enoate,<\/div>\n\n<\/p>\n<\/div>\n
B. 13\u03b1-[[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-7\u03b2,10\u03b2-dimethoxy-9-oxo-4-(propanoyloxy)-5\u03b2,20-epoxytax-11-en-2\u03b1-yl benzoate,<\/div>\n\n<\/p>\n<\/div>\n
C. 4-(acetyloxy)-13\u03b1-[[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy]-1,7\u03b2,10\u03b2-trimethoxy-9-oxo-5\u03b2,20-epoxytax-11-en-2\u03b1-yl benzoate,<\/div>\n\n<\/p>\n<\/div>\n
D. 4-(acetyloxy)-7\u03b1,13\u03b1-bis[[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10\u03b2-methoxy-9-oxo-5\u03b2,20-epoxytax-11-en-2\u03b1-yl benzoate,<\/div>\n\n<\/p>\n<\/div>\n
E. 4-(acetyloxy)-7\u03b2,13\u03b1-bis[[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10\u03b2-methoxy-9-oxo-5\u03b2,20-epoxytax-11-en-2\u03b1-yl benzoate,<\/div>\n\n<\/p>\n<\/div>\n
F. 5-[4-(acetyloxy)-2\u03b1-(benzoyloxy)-1-hydroxy-7\u03b2,10\u03b2-dimethoxy-9-oxo-5\u03b2,20-epoxytax-11-en-13\u03b1-yl] 3-tert-butyl(2R,4S,5S)-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate,<\/div>\n\n<\/p>\n<\/div>\n
G. 4-(acetyloxy)-10\u03b2,13\u03b1-bis[[(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-7\u03b2-methoxy-9-oxo-5\u03b2,20-epoxytax-11-en-2\u03b1-yl benzoate,<\/div>\n\n<\/p>\n<\/div>\n
H. 5-[4-(acetyloxy)-2\u03b1-(benzoyloxy)-1-hydroxy-7\u03b2,10\u03b2-dimethoxy-9-oxo-5\u03b2,20-epoxytax-11-en-13\u03b1-yl] 3-tert-butyl(2S,4S,5R)-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate,<\/div>\n\n<\/p>\n<\/div>\n
FP-A. 4-(acetyloxy)-1,13\u03b1-dihydroxy-7\u03b2,10\u03b2-dimethoxy-9-oxo-5\u03b2,20-epoxytax-11-en-2\u03b1-yl benzoate.<\/div>\n","protected":false},"excerpt":{"rendered":"Edition: BP 2025 (Ph. Eur. 11.6 update) General Notices (Ph. Eur. monograph 3061) Ph Eur DEFINITION Sterile concentrate for solution for infusion of Cabazitaxel acetone (3060), for human use. It complies with the monograph Parenteral preparations (0520) and the following additional requirements. Content 95.0 per cent to 105.0 per cent of the content of cabazitaxel…<\/p>\n","protected":false},"author":5,"featured_media":6620,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[175],"tags":[],"class_list":["post-6534","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-formulated-preparations-specific-monographs"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/6534","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=6534"}],"version-history":[{"count":5,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/6534\/revisions"}],"predecessor-version":[{"id":7925,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/6534\/revisions\/7925"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/6620"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=6534"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=6534"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=6534"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}}}}