液相色谱-串联质谱法测定大鼠血浆中左旋泮托拉唑钠的浓度及其毒代动力学研究

Determination of (S)-pantoprazole sodium in rat plasma and its toxicokinetics by LC-MS/MS

目的建立液相色谱-串联质谱法测定大鼠血浆中左旋泮托拉唑钠的浓度并研究其毒代动力学。方法大鼠血浆样本以乙腈沉淀蛋白后,经Chiralcel OJ-RH色谱柱(4.6 mm×150 mm,5μm);流动相为乙腈∶水=28∶72,流速为0.6 m L·min^(-1),柱温为35℃;采用Agilent 6430三重四极杆串联质谱仪,离子化方式:电喷雾-正离子(API-ES),监测方式:多反应监测,左旋泮托拉唑监测离子对384.0/199.8,非那西丁监测离子对180.0/110.0,用作内标。结果本法专属性良好;左旋泮托拉唑钠在50~30 000 ng·m L^(-1)范围内线性关系符合要求;准确度均在85%~115%,精密度在15%内。SD大鼠连续4周静脉注射给予注射用左旋泮托拉唑钠低、中、高3个剂量,左旋泮托拉唑钠动力学参数AUC_(0~4) h增长与剂量增长均呈正相关。首次和4周给药后测定无明显差异。结论本法经过方法学验证,适用于大鼠血浆中左旋泮托拉唑钠浓度的测定,可用于左旋泮托拉唑钠大鼠体内毒代动力学研究。

Objective To establish an LC-MS/MS method to determine （S） -pantoprazole sodium in rat plasma and toxicokinetics.nethods After protein precipitation with acetonitrile, the analyte and internaX standard were separated on Chiralcel OJ-RH column （4.6 mm× 150 mm, 5 μm） , with acetonitrile-water （28：72） as mobile phase at a flow 0.6 mL min-1 .Detection was carried out by electrospray positive ionization mass spectrometry in the multiple reaction monito- ring （MRM） mode.The MRM transitions of m/z384.0-m/z199.8 and m/z180.0-m/z110.0 were used to quantify （S）- pantoprazole sodium and phenacetin.Results The calibration curve was linear over the concentration range of 50- 30 000 ng mL-1.RSD was less than 15% ,and the accuracy was in the range of 85%-115%.lts AUC0-4hand Cmax were directly to proportional to doses.Conclusion The validation results showed that the established method could be applied to the deter- mination of （S） - pantoprazole sodium in plasma of rats, and was suitable to the toxicokinetics study.