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Degradation kinetics of larotaxel and identification of its degradation products in alkaline condition

摘要Larotaxel, a new taxane compound prepared by partial synthesis from 10-deacetyl baccatin Ⅲ, is active against tumors. In this research, a selective LC–MS method was developed and validated for the study of degradation kinetics of larotaxel, which was carried out in aqueous solutions with different pH (1.5, 3.0, 5.0, 6.5, 7.4, 9.0, 10 and 11.0) and temperature (0, 25, 37 and 45 °C). The linear range was 0.5–25μg/mL, the intra-and inter-day precisions were less than 7.0%, and accuracy ranged from 97.4–104.5% for each analyte. The observed rate obtained by measuring the remaining intact larotaxel was shown to follow first-order kinetics. The activation energies for degradation were 126.7 and 87.01 kJ/mol at pH 1.5 and 11, respectively. Although larotaxel was stable in pH 5, 6.5 and 7.4 buffers at 37 °C for 24 h during our study, increasing or decreasing the pH of the solutions would decrease its stabilities. Moreover, three main degradation products in alkaline condition were separated by HPLC and identified by Q–TOF–MS. The three degradation products were confirmed as 10-deacetyl larotaxel, 7, 8-cyclopropyl baccatin Ⅲ and 10-deacetyl-7, 8-cyclopropyl baccatin Ⅲ.

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作者单位 Department of Pharmaceutical Analysis, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China [1] Department of Functional Science, School of Medicine, Yangtze University, No.1 Nanhuan Road, Jingzhou City 434100, China [2]
发布时间 2017-05-05(万方平台首次上网日期,不代表论文的发表时间)
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药物分析学报(英文)

药物分析学报(英文)

2017年7卷2期

118-122页

SCIMEDLINEISTICCSCDCA

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