LC-MS法测定Beagle犬血浆中埃博霉素B及其药动学研究

目的建立液相色谱串联质谱（LC—MS）法测定Beagle犬血浆中埃博霉素B含量，分析埃博霉素B在Beagle犬体内的药动学参数。方法采用LC—MS方法测定Beagle犬接受O．05，O．10和0．15mg／kg埃博霉素B静脉给药后不同时问点的血浆浓度，药物浓度一时间数据通过DAS2．0版软件进行分析。结果血浆中埃博霉素B在O．1～18ng／mL浓度范围内线性关系良好（r=O．9999），血浆中样品提取回收率大于70％，日内和日间的精密度（RSD）均小于15％。药动学参数t1/2β分别为（76．20±7．24）、（71．41±10．62）和（64．62±9．76）h，AUCo。分别为（43．89±7．95）、（95．16±20．82）和（127．43±31．41）μg／（L·h）。结论LC—MS测定方法操作简便，专属性强，灵敏度高，适用于Beagle犬体内埃博霉素B的浓度测定和药动学研究。Beagle犬静脉注射3个剂量埃博霉索B后的药物浓度一时问数据符合二室模型特征，且埃博霉素B在犬体内半衰期较长。

Pharmacokinetic study of epothilone B in Beagle dog plasma by LC-MS

Objective Through LC-MS method to detect epothilone B in Beagle dog plasma and to perform its pharmacokinetics. Methods The plasma concentration of epothilone B was determined at different time points by LC- MS, after a single i.v. injection of 0.05, 0.10, and 0.15 mg/kg to Beagle dogs respectively. Processed data were treated by software DAS 2.0. Results The method was linear over the range of 0.1 - 18 ng/mL （r=0.9999）, the recovery of epothilone B in dog plasma was more than 70% and the relative standard （RSD） ofintra-and inter-batch precision was less than 15%. The main pharmacokinetic parameters at three concentrations were as follows： t1/2β （76.20±7.24, 71.41±10.62, 64.62± 9.76）h, AUCo-∞ （43.89±7.95, 95.16±20.82,127.43±31.41）μg/（L. h ）, respectively. Conclusion The LC-MS is a simple, sensitive and specific method for determination of epothilone B in Beagle dog plasma and its pharmacokinetic study. The data of concentration versus time fitted the two-compartmental model after i.v. injection three doses of epothilone B in Beagle dog, and drug half-life was longer in vivo.