LC-MS法测定人血浆中赖诺普利及其在药代动力学中的应用

LC-MS determination of lisinopril in human plasma and its application in pharmacokinetics

目的：建立人血浆中赖诺普利的LC-MS测定法。方法：血浆样品以10mmol／L的盐酸溶液酸化后经固相萃取小柱提取，采用选择性离子检测方法测定其血药浓度。色谱柱为Lichrospher ODS柱，流动相为甲醇-40mmol／L醋酸铵水溶液（含0.1％甲酸）（45：55），内标为依那普利拉，检测仪器为Agilent 1100四极杆质谱检测器，离子源为ESI源，检测离子为m／z：406．2（赖诺普利）、m／z：349．2（内标），裂解电压为150V。结果：在1～300ng／mL范围内赖诺普利与内标峰面积比值与浓度线性关系良好，最低定量限为1ng／mL。本方法回收率为73．46％～80．79％，批内和批间的精密度均小于15％。结论：该方法经考察符合生物样品的分析要求，可以应用于临床血药浓度的测定和药代动力学研究。

Aim：To develop an LC-MS method for the determination of lisinopril concentration in human plasma. Mothod：After being made acidified with HCl （10 mmol/L）, plasma was extracted with the solid phase extraction method using C18-cartridges and separated by RP-HPLC on a reversed phase C18 column with mobile phase consisting of CH3OH-40 mmol/L NH4AC （containing 0.1% HCOOH） water solution （45：55） and enalaprilat being used as the intemal standard. The eluate from the HPLC column was plumbed direcdy into the ESI probe. LC-MS was operated in the selected ion monitoring （SIM） mode using target ions at m/z ： 406.2 for lisinopril and m/z ： 349.2 for the intemal standard. The fragmental voltage was 150 V. Results： Calibration curves were linear over the range 1 - 300 ng/mL with 1 ng/mL of the limit of quantification for lisinopril in plasma. Recoveries of lisinopril at 2,30 and 250 ng/mL were estimated to be 73.46% ,76.67% and 80.79%, respectively. The relative standard derivation of both intrabatch and inter-batch was less than 15%. CONCLUSION： The developed method is suitable for pharmacokinetic study of lisinopril in human plasma.