LC-MS/MS法测定辛伐他汀在食蟹猴体内的血药浓度及药动学特征研究

目的:建立以LC-MS/MS法测定辛伐他汀在食蟹猴血浆中药物浓度的方法,并研究其药动学特征。方法:取食蟹猴6只,灌胃辛伐他汀8mg·kg-1,在24h内采集血浆样品,用LC-MS/MS法测定辛伐他汀血药浓度,并计算相关药动学参数。结果:辛伐他汀检测浓度的线性范围为0.5～50μg.L-1,定量下限为0.5μg.L-1,相对回收率为99%～109%,日间、日内RSD均小于6.67%。主要药动学参数t1/2为(4.5±1.0)h,Cmax为(9.0±5.5)μg.L-1,AUC0～∞为(52.39±12.52)μg.h.L-1。结论:所建方法灵敏、准确、专属性强,适用于辛伐他汀在食蟹猴体内血药浓度的测定,辛伐他汀在食蟹猴体内药动学符合单房室模型。

Plasma Drug Concentration Determination of Simvastatin in Cynomolgus Monkeys by LC - MS/MS and Its Pharmacokinetic Study

OBJECTIVE： To establish a LC- MS/MS method for the determination of simvastatin in cynomolgus monkey and study its pharmacokinetic characteristics. METHODS： 6 cynomolgus monkeys were administered intragastrically with simvastatin at a dosage of 8 mg·kg^-1 and the blood samples were collected within 24 h and determined by LC - MS/ MS, meanwhile, the relative pharmacokinetic parameters were computed. RESULTS： The linear range of simvastatin was 0.5-50 ug·L^-1 with the lowest limit of quantitation at 0.5ug·L^-1, the relative recovery at 99%- 109% and both inter- day and inner - day precision at less than 6.67%. The main pharmacokinetic parameters of simvastatin was as follows： t 12：（4.5 ± 1.0） h; Cmax （9.0± 5.5）ug·L^-1 AUC0-∞ （52.39±12.52）ug·L^-1. CONCLUSIONS： This method is sensitive, accurate, specific and suitable for the determination of plasma concentration of simvastatin in cynomolgus monkey, and the pharmacokineties of simvastatin in cynomolgus monkey is in line with one- compartment model.