کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487323 | 1114412 | 2008 | 12 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Degradation of paclitaxel and related compounds in aqueous solutions I: Epimerization
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
Paclitaxel and other taxanes have complex structures including the presence of numerous hydrolytically sensitive ester groups and a chiral center that readily undergoes epimerization thus making their kinetics complex. The present study attempts to understand the mechanism of epimerization at the 7âposition of paclitaxel, 7âepiâtaxol, 10âdeacetyltaxol, 7âepiâ10âdeacetyltaxol, baccatin III and 10âdeacetylbaccatin III. Kinetics were studied as function of temperature, pH and buffer concentration and analyzed using a stability indicating assay and LC/MS to identify degradation products. Epimerization was base catalyzed with no evidence of acid catalysis noted. The observed equilibrium constant for epimerization, K, indicated a thermodynamically more favorable Sâepimer and a small free energy change between the two epimers. For all of the compounds in this study, removal of the C10 acetyl group increases the epimerization rate in basic aqueous solutions. The observed baseâcatalyzed epimerization in near neutral to higher pH range suggests a possible rapid deprotonation/protonation of the C7 -OH, followed by a structural rearrangement through a retroaldol/aldol mechanism to form the epimer. Moreover, the rateâlimiting step of structure rearrangement most likely occurs with the formation of an enolate intermediate. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 97:1224-1235, 2008
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 3, March 2008, Pages 1224-1235
Journal: Journal of Pharmaceutical Sciences - Volume 97, Issue 3, March 2008, Pages 1224-1235
نویسندگان
Jiaher Tian, Valentino J. Stella,