{"id":4355,"date":"2025-09-26T14:46:53","date_gmt":"2025-09-26T07:46:53","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=4355"},"modified":"2025-10-02T15:10:33","modified_gmt":"2025-10-02T08:10:33","slug":"cabazitaxel-acetone","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/cabazitaxel-acetone\/","title":{"rendered":"Cabazitaxel Acetone"},"content":{"rendered":"

(Ph. Eur. monograph 3060)<\/p>\n

C_{45<\/sub>H_{57<\/sub>NO_{14<\/sub>,C_{3<\/sub>H_{6<\/sub>O\u00a0 \u00a0 \u00a0 894\u00a0 \u00a0 \u00a0 1426815-65-7<\/p>\n}}}}}

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

Taxane antineoplastic; treatment of prostate carcinoma.<\/p>\n

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

Cabazitaxel Concentrate for Infusion<\/p>\n

DEFINITION<\/h2>\n
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 benzoate as a solvate with propan-2-one.<\/p>\n
Content<\/h3>\n
97.0 per cent to 102.0 per cent (anhydrous and acetone free substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: cabazitaxel acetone CRS.<\/p>\n
B. Acetone (see Tests).<\/p>\n
TESTS<\/h2>\n
Specific optical rotation (2.2.7)<\/h3>\n
-44 to -40 (anhydrous and acetone free substance).<\/p>\n
Dissolve 0.125 g in methanol R and dilute to 25.0 mL with the same solvent.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Solvent mixture: acetonitrile R, water R previously adjusted to pH 4.0 with dilute phosphoric acid R1 (35:65 V\/V).<\/p>\n
Test solution: Dissolve 50.0 mg of the substance to be examined in 20 mL of acetonitrile R and dilute to 50.0 mL with the solvent mixture. Dilute 5.0 mL of the solution to 20.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): 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): Dissolve 50.0 mg of cabazitaxel acetone CRS in 20 mL of acetonitrile R and dilute to 50.0 mL with the solvent mixture. Dilute 5.0 mL of the solution to 20.0 mL with the solvent mixture.<\/p>\n
Reference solution (c): Dissolve 5 mg of cabazitaxel for peak identification CRS (containing impurities C, D, E, F and G) in 2 mL of acetonitrile R and dilute to 20 mL with the solvent mixture.<\/p>\n
Reference solution (d): Dissolve 5 mg of cabazitaxel for system suitability CRS (containing impurity A) in 2 mL of acetonitrile R and dilute to 20 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 3.0 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, water for chromatography R (35:65 V\/V);<\/p>\n
\u2014 mobile phase B: water for chromatography R, acetonitrile for chromatography R (25:75 V\/V);<\/p>\n\n\n\n\n\n\n
Time<\/strong>
\n(min)<\/strong><\/td>\n Mobile phase A<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n Mobile phase B<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 2<\/td>\n 100<\/td>\n 0<\/td>\n<\/tr>\n
2 – 9<\/td>\n 100 \u2192 62<\/td>\n 0 \u2192 38<\/td>\n<\/tr>\n
9 – 38<\/td>\n 62 \u2192 22<\/td>\n 38 \u2192 78<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 0.6 mL\/min.<\/p>\n
Detection: Spectrophotometer at 230 nm.<\/p>\n
Autosampler: Set at 10 \u00b0C.<\/p>\n
Injection: 10 \u03bcL.<\/p>\n
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 + E, F 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.<\/p>\n
Relative retention: With reference to cabazitaxel (retention time = about 16 min): impurity A = about 0.9; impurity C = about 1.4; impurities D + E = about 1.8; impurity F = about 1.9; impurity G = about 1.95.<\/p>\n
System suitability: Reference solution (d):<\/p>\n
\u2014 resolution: minimum 1.5 between the peaks due to cabazitaxel and impurity A.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 correction factors: multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 1.3; impurities D + E = 1.4; impurity F = 0.7;<\/p>\n
\u2014 for each impurity, use the concentration of cabazitaxel acetone in reference solution (a).<\/p>\n
Limits:<\/p>\n
\u2014 impurities A, G: for each impurity, maximum 0.2 per cent;<\/p>\n
\u2014 sum of impurities D and E: maximum 0.2 per cent;<\/p>\n
\u2014 impurities C, F: for each impurity, maximum 0.15 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 0.8 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Acetone<\/h4>\n
Head-space gas chromatography (2.2.28).<\/p>\n
Internal standard solution: Mix 1.0 mL of methyl isobutyl ketone R and 10 mL of dimethyl sulfoxide R, and dilute to 100.0 mL with dimethyl sulfoxide R.<\/p>\n
Test solution: Dissolve 0.100 g of the substance to be examined in 1.0 mL of the internal standard solution and dilute to 10.0 mL with dimethyl sulfoxide R.<\/p>\n
Reference solution: Mix 0.650 g of acetone R and 10 mL of dimethyl sulfoxide R, and dilute to 20.0 mL with dimethyl sulfoxide R. To 1.0 mL of this solution add 5.0 mL of internal standard solution and dilute to 50.0 mL with dimethyl sulfoxide R.<\/p>\n
Close the vials immediately with a butyl rubber membrane stopper coated with polytetrafluoroethylene and secured with an aluminium crimp cap. Mix to obtain a homogeneous solution.<\/p>\n
Column:<\/p>\n
\u2014 material: fused silica;<\/p>\n
\u2014 size: l = 30 m, \u00d8 = 0.32 mm;<\/p>\n
\u2014 stationary phase: trifluoropropylmethylpolysiloxane R (film thickness 1 \u03bcm).<\/p>\n
Carrier gas: helium for chromatography R.<\/p>\n
Flow rate: 2.5 mL\/min.<\/p>\n
Split ratio: 1:20.<\/p>\n
Static head-space conditions that may be used:<\/p>\n
\u2014 equilibration temperature: 110 \u00b0C;<\/p>\n
\u2014 equilibration time: 15 min;<\/p>\n
\u2014 injection time: 1 min;<\/p>\n
\u2014 injection volume: 1.0 mL.<\/p>\n
Temperature:<\/p>\n\n\n\n\n\n\n\n\n\n
<\/td>\n Time
\n(min)<\/td>\n Temperature
\n(\u00b0C)<\/td>\n<\/tr>\n
Column<\/td>\n 0 – 6<\/td>\n 35<\/td>\n<\/tr>\n
6 – 11.5<\/td>\n 35 \u2192 120<\/td>\n<\/tr>\n
11.5 – 15.5<\/td>\n 120 \u2192 220<\/td>\n<\/tr>\n
15.5 – 25.5<\/td>\n 220<\/td>\n<\/tr>\n
Injection port<\/td>\n <\/td>\n 200<\/td>\n<\/tr>\n
Detector<\/td>\n <\/td>\n \u00a0250<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Detection: FLame ionisation.<\/p>\n
Identification of peaks: Use the chromatogram obtained with the reference solution to identify the peak due to acetone.<\/p>\n
Relative retention: With reference to methyl isobutyl ketone (retention time = about 9.7 min): acetone = about 0.4.<\/p>\n
System suitability: Reference solution:<\/p>\n
\u2014 repeatability: maximum relative standard deviation of 3.0 per cent determined on 3 injections.<\/p>\n
Calculation of percentage content: Use the internal standard method.<\/p>\n
Limit:<\/p>\n
\u2014 acetone: 5.0 per cent m\/m to 7.0 per cent m\/m.<\/p>\n
Water (2.5.32)<\/h4>\n
Maximum 1.0 per cent, determined on 200 mg by direct sample introduction. [Stir for a minimum of 180 s.]\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
Bacterial endotoxins (2.6.14, Method D)<\/h4>\n
Solution A: A 0.20 mg\/mL solution of the substance to be examined in a 0.25 per cent V\/V solution of polysorbate 80 R.<\/p>\n
Solution C: A 0.5 per cent V\/V solution of polysorbate 80 R.<\/p>\n
ASSAY<\/h2>\n
Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n
Injection: Test solution and reference solution (b).<\/p>\n
Calculate the percentage content of C_{45<\/sub>H_{57<\/sub>NO_{14<\/sub> taking into account the assigned content of cabazitaxel acetone CRS.<\/p>\n}}}
STORAGE<\/h2>\n
At a temperature of 2 \u00b0C to 8 \u00b0C.<\/p>\n
LABELLING<\/h2>\n
The label states, where applicable, that the substance is suitable for use in the manufacture of parenteral preparations.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities A, C, D, E, F, G.<\/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, H.<\/p>\n
$\"Cabazitaxel$ <\/p>\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,<\/p>\n
$\"Cabazitaxel$ <\/p>\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,<\/p>\n
$\"Cabazitaxel$ <\/p>\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,<\/p>\n
$\"Cabazitaxel$ <\/p>\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,<\/p>\n
$\"Cabazitaxel$ <\/p>\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,<\/p>\n
$\"Cabazitaxel$ <\/p>\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,<\/p>\n
$\"Cabazitaxel$ <\/p>\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,<\/p>\n
$\"Cabazitaxel$ <\/p>\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.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 3060) C45H57NO14,C3H6O\u00a0 \u00a0 \u00a0 894\u00a0 \u00a0 \u00a0 1426815-65-7 Action and use Taxane antineoplastic; treatment of prostate carcinoma. Preparation Cabazitaxel Concentrate for Infusion DEFINITION 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 benzoate as a solvate with propan-2-one. Content 97.0 per cent to 102.0 per cent (anhydrous and acetone free substance). CHARACTERS Appearance White or almost white powder. Solubility…<\/p>\n","protected":false},"author":2,"featured_media":4416,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-4355","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\/4355","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=4355"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/4355\/revisions"}],"predecessor-version":[{"id":5273,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/4355\/revisions\/5273"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/4416"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=4355"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=4355"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=4355"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n97.0 per cent to 102.0 per cent (anhydrous and acetone free substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or almost white powder.<\/p>\n

Solubility<\/h3>\nPractically insoluble in water, soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\nA. Infrared absorption spectrophotometry (2.2.24).<\/p>\nComparison: cabazitaxel acetone CRS.<\/p>\nB. Acetone (see Tests).<\/p>\n

TESTS<\/h2>\n

Specific optical rotation (2.2.7)<\/h3>\n-44 to -40 (anhydrous and acetone free substance).<\/p>\nDissolve 0.125 g in methanol R and dilute to 25.0 mL with the same solvent.<\/p>\n

Water (2.5.32)<\/h4>\nMaximum 1.0 per cent, determined on 200 mg by direct sample introduction. [Stir for a minimum of 180 s.]\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on 1.0 g.<\/p>\n

Bacterial endotoxins (2.6.14, Method D)<\/h4>\nSolution A: A 0.20 mg\/mL solution of the substance to be examined in a 0.25 per cent V\/V solution of polysorbate 80 R.<\/p>\nSolution C: A 0.5 per cent V\/V solution of polysorbate 80 R.<\/p>\n

STORAGE<\/h2>\nAt a temperature of 2 \u00b0C to 8 \u00b0C.<\/p>\n

LABELLING<\/h2>\nThe label states, where applicable, that the substance is suitable for use in the manufacture of parenteral preparations.<\/p>\n

Content<\/h3>\n
97.0 per cent to 102.0 per cent (anhydrous and acetone free substance).<\/p>\n

Appearance<\/h3>\n
White or almost white powder.<\/p>\n

Solubility<\/h3>\n
Practically insoluble in water, soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n

IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: cabazitaxel acetone CRS.<\/p>\n
B. Acetone (see Tests).<\/p>\n

Specific optical rotation (2.2.7)<\/h3>\n
-44 to -40 (anhydrous and acetone free substance).<\/p>\n
Dissolve 0.125 g in methanol R and dilute to 25.0 mL with the same solvent.<\/p>\n

Water (2.5.32)<\/h4>\n
Maximum 1.0 per cent, determined on 200 mg by direct sample introduction. [Stir for a minimum of 180 s.]\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

Bacterial endotoxins (2.6.14, Method D)<\/h4>\n
Solution A: A 0.20 mg\/mL solution of the substance to be examined in a 0.25 per cent V\/V solution of polysorbate 80 R.<\/p>\n
Solution C: A 0.5 per cent V\/V solution of polysorbate 80 R.<\/p>\n

STORAGE<\/h2>\n
At a temperature of 2 \u00b0C to 8 \u00b0C.<\/p>\n

LABELLING<\/h2>\n
The label states, where applicable, that the substance is suitable for use in the manufacture of parenteral preparations.<\/p>\n