LC-MS/MS测定大鼠体内的紫杉醇和紫杉醇天冬氨酸聚合物并研究其药动学
Determination of Paclitaxel and polyaspartate Paclitaxel conjugate in the rat plasma by LC-MS/MS and study on their pharmacokinetic
作者：高杨杨;张晞倩;王微;王婷;王凌;蒋学华;
Author：
收稿日期： 年卷（期）页码：2017,32(01):-66-70
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：紫杉醇;液质联用/质谱;聚合物;药动学;含量测定;非线性动力学;血药浓度
Key words：
基金项目：
中文摘要
目的采用LC-MS/MS法测定大鼠血浆中的聚合型紫杉醇(CPTX)和游离型紫杉醇(PTX),并用于评价给予大鼠单剂量尾静脉注射紫杉醇天冬氨酸聚合物(Pexil)的药动学。方法单剂量尾静脉给予SD大鼠高、中、低剂量Pexil后,于0~336 h间隔采集血浆;采用LC-MS/MS法测定血浆中CPTX和PTX的浓度,用DAS 2.1.1软件计算其药动学参数。结果给予大鼠单剂量高、中、低剂量Pexil后,CPTX和PTX的主要药动学参数:Cmax分别为989.7±49.4、465.3±32.2、214.1±28.0mg·L~(-1)和7.489±1.411、2.579±0.600、1.640±0.431 mg·L~(-1);AUC0→t分别为12.81±1.22、5.451±0.79、1.98±0.57 g·L~(-1)·h和67.38±10.38、27.91±7.45、13.42±5.04 mg·L~(-1)·h;Tmax分别为0.50、0.50、0.50 h和0.50、0.50、0.63 h;t1/2分别为506.94±803.37、289.07±356.17、283.35±257.79 h和39.14±32.11、5.50±1.29、4.35±1.34 h。结论所用方法专属性强、灵敏度高、结果准确;大鼠经单剂量尾静脉注射Pexil后,体内CPTX和PTX的代谢显示非线性动力学性质,♀♂大鼠间的药动学行为仅在高剂量时有显著性差异。
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