液相色谱-串联质谱法测定人血浆中奥美拉唑的血药浓度及其药动学

目的:建立液相色谱-串联质谱法测定人血浆中奥美拉唑的血药浓度并进行药动学研究。方法:以兰索拉唑为内标,血浆样品经乙腈沉淀后,经LC-MS/MS分离分析。采用Diamonsil C₁₈柱(2.1 mm×150 mm,5 μm),甲醇-水(含0.01%甲酸)(67:33)为流动相;流速为0.3 ml·min^-1,采用电喷雾离子源(ESI),以多反应监测方式(MRM)进行负离子监测,奥美拉唑和兰索拉唑的定量分析离子对分别为m/z 344.2/193.8,367.9/163.8。结果:奥美拉唑在3.38~2 110.00 ng·ml^-1 (r=0.997 1)范围内线性关系良好,最低定量限为3.38 ng·ml^-1,方法回收率在92.48%~99.39%,日内(n=5)RE均小于3.96%,日间(n=15)RE均小于6.41%。结论:该方法快速简便,灵敏准确,可用于奥美拉唑血药浓度监测和药动学研究。

Determination of omeprazole concentration in human plasma by LC-MS/MS and pharmacokinetics study

OBJECTIVE To establish a high performance liquid chromatography tandem mass spectrometry (LC-MS/MS) method for determination of omeprazole (OM) in human plasma, and apply to clinical study on pharmacokinetics.METHODS Plasma samples were precipitated with acetonitrile and determined by LC-MS/MS using lansoprazole as an internal standard. Separation was carried out on a Diamonsil C₁₈ column (2.1 mm×150 mm, 5 μm) with a mobile phase of methanol-water (containing 0.01% formic acid) (67:33) and at a flow rate of 0.3 ml·min^-1. ESI was performed in MRM negative mode using target ions at m/z 344.2/193.8 for OM, and 367.9/163.8 for lansoprazole, respectively.RESULTS Calibration curves of OM were obtained in range of 3.38-2 110.00 ng·ml^-1 (r=0.997 1) with good linearity. The lower limit of quantization was 3.38 ng·ml^-1. The relative recovery was 92.48%-99.39%, and intra- and inter-day RE less than 6.41%.CONCLUSION This method has good sensitivity and precision, and is suitable for plasma concentration monitoring and pharmacokinetic studies of OM.