Chiral-LC-MS/MS法同时测定人血浆中兰索拉唑对映体的浓度

目的:建立Chiral-LC-MS/MS法同时测定人血浆中S-兰索拉唑和R-兰索拉唑的浓度.方法:以乙腈作为蛋白质沉淀剂,对血浆中的兰索拉唑对映异构体进行Chiral-LC-MS/MS分析.色谱柱:Chiralpak IC柱(4.6 mm×150 mm,5μm),柱温为30℃,流动相为10 mmol·L-1醋酸铵(含0.05%醋酸)-乙腈(50:50,v/v),兰索拉唑对映异构体在9.0 min内可达到基线分离.采用AB QTRAP 5500质谱仪,使用电喷雾离子化(ESI)正离子模式,兰索拉唑和内标(埃索美拉唑)的多反应监测(MRM)扫描离子对分别为m/z 370.1→252.1和346.1→198.1.结果:该方法无明显的基质效应,S-兰索拉唑和R-兰索拉唑在标准曲线范围内线性关系良好,标准曲线的线性范围均为20.00~10000 ng·mL-1,准确度在±15%,批内和批间精密度均小于10%.在兰索拉唑对映体的储存、 处理和分析过程中没有发现两者间的手性转化,测定过程中各化合物稳定性符合要求.结论:建立了简单、高选择性的Chiral-LC-MS/MS方法,可用于同时测定人血浆中的兰索拉唑对映体的浓度.

Determination of Lansoprazole Enantiomers in Human Plasma by a Chiral-LC-MS/MS Method

Objective: A simple and enantioselective method was developed and validated for simultane-ous determination of S-lansoprazole and R-lansoprazole in human plasma by chiral liquid chromatography with tandem mass spectrometry (Chiral-LC-MS/MS). Methods: Lansoprazole enantiomers and internal stan-dard (esomeprazole) were extracted from plasma using acetonitrile as the protein precipitating agent. Base-line chiral separation was achieved within 9.0 min on a Chiralpak IC column (150 mm×4.6 mm, 5μm) at 30℃. The mobile phase was consisted of 10 mmol·L-1 ammonium acetate solution containing 0.05% acetic acid/acetonitrile (50:50, v/v). The mass spectrometric analysis was performed using an AB QTRAP 5500 mass spectrometercoupled with an electrospray ionization source in positive ion mode. The multiple reaction monitoring transitions of m/z 370.1→252.1 and 346.1→198.1 were used to quantify lansoprazole enan-tiomers and esomeprazole, respectively. Results: For each enantiomer, no apparent matrix effect was found. All the analytes showed good linearity between 20.00-10000 ng·mL-1. The RSD for intra- and inter- preci-sions and accuracy were within 10.0%. No chiral inversion was observed during the procedures of sample storage, preparation or analysis. Analytes were stable during the study. Conclusion: A simple and selective chiral-LC-MS/MS method has been successfully developed for the simultaneous determination of lansopra-zole enantiomers in human plasma.