HPLC-MS/MS法测定人血浆中右旋雷贝拉唑和左旋雷贝拉唑浓度及其人体药动学研究  

Determination of dexrabeprazole and levrabeprazole in human plasma by HPLC-MS/MS and its pharmacokinetic study

作　　者：李相鸿[1,2,3] 谢海棠[1,2,3] 梁大虎[1,2,3] 孙华[1,2,3] 周理想[1,2,3] 戴敏[1,2] 杨斌 王伟佳[1,2] 沈杰[1,2] 赵亚男[1,2,3] LI Xiang-hong;XIE Hai-tang;LIANG Da-hu;SUN Hua;ZHOU Li-xiang;DAI Min;YANG Bin;WANG Wei-jia;SHEN Jie;ZHAO Ya-nan(Drug Clinical Trial Institution of Yijishan Hospital of Wannan Medical College,Wuhu 241000,China;Drug Clinical Evaluation Center of Anhui Province,Wuhu 241000,China;Clinical Pharmacy Teaching and Research Department of Wannan Medical College,Wuhu 241000,China)

机构地区：[1]皖南医学院弋矶山医院药物临床试验机构,芜湖241000 [2]安徽省药物临床评价中心,芜湖241000 [3]皖南医学院临床药学教研室,芜湖241000

出　　处：《中国新药杂志》2021年第1期43-49,共7页Chinese Journal of New Drugs

摘　　要：目的:利用手性色谱柱建立高效液相色谱-串联质谱(HPLC-MS/MS)法同时测定人血浆中右旋雷贝拉唑(dexrabeprazole,DLBLZ)和左旋雷贝拉唑(levrabeprazole,LLBLZ)的浓度,并用于注射用右旋雷贝拉唑钠的人体药动学研究。方法:采用AB Sciex API4000液质联用仪,ESI离子源,大赛璐CHIRALPAK?IC(250 mm×4.6 mm,5μm)手性色谱柱,流动相为乙腈-10 mmol·L^(-1)醋酸铵(75∶25,v/v),流速为1 m L·min-1,以同位素氘代右旋雷贝拉唑(D-DLBLZ)为内标,血浆样品经乙腈沉淀蛋白后取上清液进样2μL分析。入选40例健康志愿者参与注射用右旋雷贝拉唑钠人体药动学研究。结果:建立的HPLC-MS/MS法在1.00~1500μg·L^(-1)范围内DLBLZ线性关系良好,在1.50~1500μg·L^(-1)范围内LLBLZ线性关系良好。对两待测物进行全面的方法学验证,结果显示标准曲线、选择性、最低定量限、精密度与准确度、回收率、基质效应和稳定性等均满足检测要求。结论:本实验室建立的HPLC-MS/MS法选择性强、灵敏度高、手性拆分分离度好,适用于人血浆中DLBLZ和LLBLZ的浓度测定,并成功应用于注射用右旋雷贝拉唑钠的人体药动学研究。Objective:An HPLC-MS/MS method was developed for simultaneous determination of dexrabeprazole and levrabeprazole concentrations in human plasma by using a chiral chromatographic column.It was used in the pharmacokinetic study of dexrabeprazole sodium for injection.Methods:AB Sciex API4000 liquid-mass spectrometer with ESI ion source was selected and the Daicel CHIRALPAK?IC(250 mm×4.6 mm,5μm)chiral chromatographic column were used with the mobile phase of acetonitrile-10 mm ammonium acetate(75∶25,v/v)at a flow rate of 1 m L·min-1.The isotopic[2H3]-dexrabeprazole was used as internal standard.The plasma samples were analyzed using 2μL supernatant after the protein was precipitated by acetonitrile.Forty healthy volunteers participated in the pharmacokinetic study of dextrorabeprazole sodium for injection.Results:The established HPLC-MS/MS method has good linear relationship for dexrabeprazole in the range of 1.00~1500μg·L^(-1),and for levrabeprazole in the range of 1.50~1500μg·L^(-1).The results show that the linearity,selectivity,lower limit of quantification,precision and accuracy,recovery,matrix effect as well as stability all meet the test requirements.Conclusion:The HPLC-MS/MS method established in this laboratory has strong selectivity,high sensitivity and good chiral separation.It is suitable for the concentration determination of dexrabeprazole and levrabeprazole in human plasma,and has been successfully applied to the pharmacokinetic study of dexrabeprazole sodium for injection.

关 键 词：高效液相色谱-串联质谱法 雷贝拉唑 右旋雷贝拉唑 左旋雷贝拉唑 血浆 药动学 

分 类 号：R969.1[医药卫生—药理学]