辛伐他汀在人、食蟹猴和大鼠血浆中稳定性的种属差异

Species-related Stability Difference of Simvastatin in Human,Cynomolgus Monkey and Rat Plasma

关键词:  辛伐他汀  血浆稳定性  种属差异  LC-MS/MS

Key words:  simvastatin  plasma stability  species difference  LC-MS/MS

摘要:

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0.5～50 μg·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。

Abstract:

OBJECTIVE To establish an LC-MS/MS method for the determination of simvastatin in cynomolgus monkey plasma,and compare its stability differences in three species of human, cynomolgus monkey and rat plasma.METHODS Validated LC-MS/MS method was established and used for analysis of simvastatin samples which were prepared in the plasma of three species and stored under different conditions.RESULTS The linearity of calibration curve was 0.5-50 μg·L-1 and the limit of quantitation was 0.5 μg·L-1. The inter- and inner- day precision were below 6.67% and the accuracy of the method was 99-109%. Drug concentration of cynomolgus monkey plasma samples being placed 24 h at room temperature decreased 70%，drug concentration of SD rat plasma samples being placed 4 h and 24 h at room temperature decreased 75% and 80%,drug concentration of human plasma samples being placed 24 h at room temperature decreased 30%.Samples frozen at -80 ℃ were mostly stable, except for that of rat plasma samples.CONCLUSION The established method is suitable for the determination of simvastatin in cynomolgus monkey plasma. Stability of simvastatin varies greatly in different plasma and shows species-related differences.