摘要
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0.05,0.10和0.15 mg/kg埃博霉素B静脉给药后不同时间点的血浆浓度,药物浓度-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0.1～18 ng/mL浓度范围内线性关系良好(r=0.9999),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t_(1/2β)分别为(76.20±7.24)、(71.41±10.62)和(64.62±9.76)h,AUC_(0-∞)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个剂量埃博霉素B后的药物浓度-时间数据符合二室模型特征,日族博霉素B在犬体内半衰期较长。
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.
出处
《世界临床药物》
CAS
2012年第9期539-543,共5页
World Clinical Drug
