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.
出处
《中国测试》
北大核心
2017年第10期53-58,共6页
China Measurement & Test
