目的建立液相色谱-串联质谱法测定犬血浆中左旋泮托拉唑钠的浓度并研究其毒代动力学。方法犬血浆样本以乙腈沉淀蛋白后,选用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℃;选用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:MRM,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。结果本分析方法专属性良好;左旋泮托拉唑钠在50~30 000 ng·m L~(-1) 内线性关系符合要求;准确度均在85%~115%,精密度RSD在15%内。Beagle犬连续4周静脉注射给予注射用左旋泮托拉唑钠低、中、高(10、20、40 mg·kg~(-1) ·d~(-1) )3个剂量,左旋泮托拉唑钠动力学参数AUC_(0-4h)和ρ_(max)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。结论本法经方法学验证,适用于犬血浆中左旋泮托拉唑钠浓度测定,可用于左旋泮托拉唑钠犬体内毒代动力学研究。 Objective To establish a liquid chromatography-tandem mass spectrometry (HPLC-tandem mass spectrometry) method for the determination of pantoprazole sodium in canine plasma and to study its toxicokinetics. Methods After the protein was precipitated by acetonitrile, the chromatographic separation was performed on a CHIRALCEL OJ-RH column (4.6 mm × 150 mm, 5 μm). The mobile phase consisted of acetonitrile-water = 28:72 and the flow rate was 0.6 m L · min -1 The column temperature was 35 ℃. The Agilent 6430 triple quadrupole tandem mass spectrometer was used. The ionization mode was electrospray-positive ion (API-ES). The monitoring mode was MRM. The ion pair was monitored by Lp pantoprazole ion pair 384.0 / 199.8, Phenacetin monitored ion pair 180.0 / 110.0 for internal standard use. Results The analytical method was of good specificity. L-pantoprazole sodium was linear in the range of 50 ~ 30 000 ng · m L -1 with accuracy of 85% -115% and precision of RSD of 15% Inside. Beagle dogs were given intravenous injection of L-pantoprazole sodium at low, medium and high doses (10, 20 and 40 mg · kg -1 · d -1) for 4 weeks continuously. The kinetic parameters of razolamide, AUC_ (0-4h) and ρ_ (max), were positively correlated with the increase of dose. There was no significant difference between the first and the fourth week after administration. Conclusion This method is validated by methodology and is suitable for the determination of pantoprazole sodium in canine plasma. It can be used to study the toxicokinetics of L-pantoprazole sodium in dogs.