HPLC-MS/MS法同时测定人血浆中奥美拉唑及其代谢物  

Research on simultaneous quantitative determination method of omeprazole and metabolites in human plasma by HPLC-MS/MS

作　　者：王曼[1,2] 王鸿芡 秦永平 梅亚君[1,2] 南峰 向瑾[2] 余勤[2] 梁茂植[2] 张梅[1] 罗明军[3] 

机构地区：[1]成都中医药大学药学院中药材标准化教育部重点实验室中药资源系统研究与开发利用省部共建国家重点实验室培育基地,四川成都611137 [2]四川大学华西医院国家药物临床试验机构临床药理研究室,四川成都610041 [3]重庆赛诺生物药业股份有限公司,重庆401554

出　　处：《中国测试》2017年第10期53-58,共6页China Measurement & Test

摘　　要：建立HPLC-MS/MS法测定人血浆中奥美拉唑(OPZ)及代谢物奥美拉唑砜(S-OPZ)、5-羟基奥美拉唑(HOPZ)的浓度,以用于奥美拉唑的药代动力学研究。采用Phenomenex Gemini C18(50 mm×3.0 mm,5μm)色谱柱,乙腈-水(体积比40∶60)为流动相,流量0.2 m L/min,以d3-奥美拉唑(d3-OPZ)作内标,血浆样本用二氯甲烷∶异丙醇(体积比97∶3)萃取,采用ESI源,正离子MRM模式检测。OPZ在0.5~600 ng/m L范围内,S-OPZ和H-OPZ在0.25~300 ng/m L范围内线性良好;OPZ、S-OPZ、H-OPZ及IS的保留时间分别为3.19,4.18,1.96,3.19 min左右;萃取回收率在53.8%~84.6%;高浓度血浆样品稀释4倍测定不影响结果 ;精密度、基质效应经内标校准后均合格;稳定性各项数据均符合相关要求。该法快速、灵敏、专属性强、重现性好,适用于奥美拉唑及其代谢物的血药浓度测定。To develop an accurate and sensitive HPLC-MS/MS method for simultaneous determination of omeprazole （OPZ） and its active metabolites omeprazole sulfone （S-OPZ）, 5- hydroxy omeprazole （H-OPZ） in human plasma to perform OPZ human pharmacokinetic studies.The extractives were separated on a Phenomenex Gemini C18 （50mm×3.0mm, 5 p,m） column,and the mobile phase consisting of a mixture of acetonitrile： water （40：60, V/V） was delivered at a flow rate of 0.2 mL/min. D3-omeprazole was used as the internal standard. Human plasma samples were extracted with dichloromethane： isopropanol （97：3,V/V）. An electrospray ionization （ESI） source was applied and operated in the positive multiple reaction monitoring （MRM） mode. In the plasma samples, the calibration curve for OPZ and H-OPZ,S-OPZ was in the range of 0.5-600 ng/mL and 0.25-300 ng/mL. The retention time of omeprazole, omeprazole sulfone, 5-hydroxy omeprazole and IS were 3.19, 4.18, 1.96 and 3.19 rain, respectively; Pretreatment recovery was 53.8%-84.6%; accuracy, precision and matrixes effect after internal standard calibration are comply with relevant requirements. The plasma samples dilute 4 times shall not affect the results. Data about all stability study fitted the request. The method is simple, rapid, sensitive and accurate for the determination of omeprazole and metabolites in human plasma and to be suitable for the pharmacokinetic study.

关 键 词：奥美拉唑 奥美拉唑砜 5-羟基奥美拉唑 HPLC-MS/MS 血药浓度 

分 类 号：O657.32[理学—分析化学]