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目的建立LC-MS/MS法测定辛伐他汀在食蟹猴血浆中的检测方法学,并比较其在人、食蟹猴和大鼠3种动物血浆中的稳定性差异。方法建立LC-MS/MS分析食蟹猴血浆辛伐他汀药物浓度的方法学;配制辛伐他汀3种动物血浆样品,分别于室温放置4 h、24 h及-80℃冻存1个月,并定量检测。结果辛伐他汀线性范围为0.5~50μg.L-1,定量下限为0.5μg.L-1,相对回收率99~109%,日内、日间精密度均小于6.67%;辛伐他汀在食蟹猴血浆中室温放置24 h样品的药物浓度降低70%左右;在SD大鼠血浆中室温放置4 h和24 h样品的药物浓度分别降低75%和80%左右;在人血浆中室温放置24 h的样品的药物浓度降低30%左右;-80℃冻存条件下,除大鼠血浆样品外,其他样品基本稳定。结论所建立的方法适用于小体积实验动物辛伐他汀药动学研究;辛伐他汀在不同动物种属血浆中的稳定性存在很大差异。
Objective To establish a method for the determination of simvastatin in plasma of cynomolgus monkey by LC-MS / MS and to compare the stability of simvastatin with that of human, cynomolgus and rat plasma. Methods The LC-MS / MS method was used to analyze the plasma concentrations of simvastatin in cynomolgus monkeys. Three plasma samples of simvastatin were prepared and stored at room temperature for 4 h, 24 h and at -80 ℃ for 1 month respectively. And quantitative detection. Results The linear range of simvastatin was 0.5-50μg.L-1, the lower limit of quantification was 0.5μg.L-1, the relative recovery was 99-109%, the intra-day and inter-day precision were less than 6.67% The concentration of drug in monkey plasma at room temperature for 24 h dropped by about 70%. The concentration of drug in SD rat plasma at room temperature for 4 h and 24 h decreased by 75% and 80%, respectively. After being stored in human plasma at room temperature for 24 h Of the sample drug concentration decreased by about 30%; -80 ℃ frozen conditions, except for the rat plasma samples, other samples were basically stable. Conclusion The established method is suitable for pharmacokinetics of simvastatin in small-volume experimental animals. Simvastatin has great differences in the stability of plasma in different animal species.