大鼠血浆中硫醚-雷贝拉唑浓度测定方法的建立和验证

Establishment and validation of a method for determination of rabeprazole thioether in rat plasma

目的：建立高效液相色谱-质谱法（HPLC-MS）测定大鼠血浆中硫醚-雷贝拉唑浓度。方法：血浆样品以地西泮为内标,乙腈沉淀蛋白处理,采用HPLC-MS法检测。色谱柱为InertsilODS-3（4.6 mm×150 mm,5μm）,流动相为乙腈-5mmol·L-1醋酸铵溶液（65∶35）,流速为0.7 ml·min-1。用ESI离子源,正离子检测模式,选择监测质荷比（m/z）为344.2（硫醚-雷贝拉唑）和285.1（内标）的离子峰。结果：硫醚-雷贝拉唑在2~800 ng·ml-1浓度范围内线性关系良好,最低定量限为2ng·ml-1。提取回收率为102.9%~109.3%,日内、日间精密度分别小于3.9%和6.4%。结论：本方法专属性强,灵敏度高,简便易行,可用于雷贝拉唑大鼠体内药动学的研究。

OBJECTIVE To establish HPLC-MS method for determination of rabeprazole thioether in rat plasma.METHODS Diazepam was used as an internal standard and acetonitrile as the extraction solvent.Rabeprazole thioether and diazepam in plasma by HPLC-MS assay were separated on an Inertsil ODS3（4.6 mm×150 mm,5μm）column,eluted with mobile phase of acetonitrile-5 mmol·L-1 ammonium acetate water solution（65∶35）,and a flow rate of 0.7 ml·min-1.MS system with an electrospray ionization（ESI）source was used as the detector and was operated in a positive ion mode.Selected ion monitoring（SIM）was performed and the m/z of ions selected for quantification were 344.2（rabeprazole thioether）and 285.1（internal standard）.RESULTS The calibration curve of rabeprazole thioether was linear over the concentration range of 2-800 ng·ml-1.The lower limit of quantitation was 2 ng·ml-1.The extraction recovery was 102.9%-109.3%,the intra and inter day precisions were less than 3.9% and 6.4%.CONCLUSION This method was specificity,sensitive,convenient and can be used for pharmacokinetic study of rabeprazole in rat plasma.