液相色谱-串联质谱法测定人血浆中兰索拉唑及其代谢物浓度

Determination of lansoprazole and its major metabolites in human plasma by RRLC/MS/MS

目的建立液相色谱-串联质谱同时测定人血浆中兰索拉唑及其代谢物兰索拉唑砜、5-羟基兰索拉唑浓度的方法。方法用Agilent SB-C18色谱柱,流动相为0.002 mol.L-1乙酸铵(用甲酸调pH为4)-乙腈(60∶40,v/v),流速为0.3 mL.min-1。用正离子电离,多离子反应监测进行定量分析。结果兰索拉唑、兰索拉唑砜、5-羟基兰索拉唑线性范围分别为5～3044,1.5～550,2～549.5 ng.mL-1,三者日内、日间精密度均小于10%,三者的提取回收率为81.55%～98.74%(RSD<10%)。结论本方法灵敏、准确、快速,可用于人血浆中兰索拉唑及其代谢物浓度的测定和药代动力学研究。

Objective To establish a rapid and sensitive liquid chromatography-mass spectrometry（RRLC/MS/MS） method for the determination of lansoprazole and its two metabolites in human plasma.Methods Agilent SB C18（2.1 mm×100 mm,3.5 μm） column was used at 40 ℃,with a mobile phase of 2 mmol·L-1 ammonium acetate-acetonitrile solution（60∶40） at a flow-rate of 0.3 mL·min-1.An injection volume of 5 μL was used.Quantitaion was performed using multiple reaction monitoring（MRM）.Results The linear calibration curves were obtained in the range of 5-3044 ng·mL-1 for lansoprazole,in the rage of 1.5-550 ng·mL-1 for lansoprazole sulphone and in the rage of 2-549.5 ng·mL-1 for 5-hydroxy lansoprazole.The extraction recovery for lansoprazole and two metabolites were ranged from 81.55%-98.74%（RSD10%）.Conclusion The analytical method appeared to be accurate,sensitive,and convenient for the determination of lansoprazole and its two metabolites.It is suitable for therapeutic drug monitoring and pharmacokinetic study of lansoprazole and its two metabolites.