液相色谱串联质谱法测定犬血浆中埃索美拉唑质量浓度及药动学研究

目的建立液相色谱联用质谱法(LC-MS/MS)测定犬血浆中埃索美拉唑(esomeprazole,EMZ)药物质量浓度,并用于其药动学进行研究。方法以地西泮为内标,血浆经乙腈沉淀蛋白处理,色谱柱为Shim-pack XR-ODS柱(100mm×2mm,5μm);流动相为乙腈:2mmol.L-1乙酸铵(含1mL.L-1甲酸);流速0.3mL.min-1;质谱条件:电喷雾离子化电离源ESI,正离子多反应检测,检测离子分别为346.2→198.2 m/z(埃索美拉唑)和285.2→193.2 m/z(地西泮)。采用DAS 2.0软件进行药动学参数估算。结果埃索美拉唑质量浓度在0.5～3 000μg.L-1范围内呈良好线性关系(r>0.99),最低定量限(LLOQ)为0.5μg.L-1,平均回收率为100.8%±6.7%,高、中、低3种质量浓度的日内和日间精密度实验RSD均小于15%。埃索美拉唑主要药动学参数AUC0-36,Cmax,tmax,t1/2z,CLz/F分别为(99 435.28±2 473.73)μg.h.L-1,(2 478.75±425.69)μg.L-1,(1.44±0.32)h,(3.41±2.86)h,(0.46±0.14)L.h-1.kg-1。结论该实验建立的分析方法专属性好,灵敏度高,准确快捷,适用于埃索美拉唑犬体内生物样品的分析。

Determination of esomeprazole in dog plasma by LC-MS-MS and study on its pharmacokinetics

Objective To determine the plasma level of esomeprazole in dog by LC-MS/MS and to study its pharmacokinetics.Method The plasma was precipitated with acetonitril,and diazepam was used as an internal standard.The plasma samples were chromatographed on a Shim-pack XR-ODS(100mm×2mm,5μm)column with a mobile phase consisting of acetonitrile and 2mmol.L-1 ammonium acetate(containing 1mL.L-1 formic acid).The flow rate was 0.3mL.min-1.ESI was applied and operated in a positive ion multiple-reaction monitoring mode.The detected ions were m/z346.2→198.2(esomeprazole),m/z285.2→193.2(diazepam).The pharmacokinetic parameters were calculated with DAS 2.0practical pharmacokinetics program.Results The linear calibration curve of esomeprazole in plasma was obtained in a concentration range from 0.5to 3 000μg.L-1(r>0.99).The average recovery of esomeprazole was 100.8%±6.7%,the intra-day and inter-day RSDs were both less than 15%.The parameters of AUC0-36,Cmax,tmax,t1/2z,CLz/Ffor esomeprazole were(99 435.28±2 473.73)μg.h.L-1,(2 478.75±425.69)μg.L-1,(1.44±0.32) h,(3.41±2.86)h,(0.46±0.14)L.h-1.kg-1,respectively.Conclusion The method has been proved to be sensitive,simple,rapid and suitable for the determination of esomeprazole in dogs.