Degradation of paclitaxel and related compounds in aqueous solutions III: Degradation under acidic pH conditions and overall kinetics.
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| Abstract |
Paclitaxel and related taxanes are complex molecules with numerous hydrolysable ester groups, possible epimerization at the 7-position, and possessing a strained oxetane ring, a possible site for acid-catalyzed cleavage. Presented here is the stability of paclitaxel, 10-deacetylbaccatin III, baccatin III, and N-benzoyl-3-phenylisoserine ethyl ester in aqueous solution over a pH range of 1-5 at various temperatures. Analysis of various samples was by HPLC-UV and LC-MS. Baccatin III, 10-deacetylbaccatin III, and N-benzoyl-3-phenylisoserine ethyl ester were found to undergo acid catalysis since pH-rate profiles all followed a first-order dependency in hydrogen ion concentration. No evidence of any epimerization was noted at acidic pH values. Baccatin III and 10-deacetylbaccatin III showed similar degradation rates with possible products being possible dehydration around the 13-hydroxy group and cleavage of the oxetane ring. Cleavage of the 10-acetyl group of baccatin III was a minor initial pathway. N-Benzoyl-3-phenylisoserine ethyl ester degraded significantly slower than both 10-deacetylbaccatin III and baccatin III. At pH 2, paclitaxel degraded at a rate between that of N-benzoyl-3-phenylisoserine ethyl ester and 10-deacetylbaccatin III. The pH of maximum stability for all compounds appeared to be around pH 4.
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| Authors | Jiaher Tian, Valentino J Stella |
| Journal | Journal of pharmaceutical sciences (J Pharm Sci) Vol. 99 Issue 3 Pg. 1288-98 (Mar 2010) ISSN: 1520-6017 [Electronic] United States |
| PMID | 19743504 (Publication Type: Journal Article) |
| Copyright | 2009 Wiley-Liss, Inc. and the American Pharmacists Association |
| Chemical References |
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