Beagle犬血浆中酮咯酸的LC-MS/MS法测定及其药动学

Determination of Ketorolac in Beagle Dog Plasma by LC-MS/MS and Its Pharmacokinetics

建立了液相色谱-串联质谱法测定Beagle犬血浆中的酮咯酸.以格列吡嗪为内标,采用ESI源正离子模式、多反应监测进行定量分析.监测离子对为m/z 256.4→m/z 105.1（酮咯酸）和m/z 446.4→m/z 321.1（格列吡嗪）.酮咯酸在0.05～10 μg/ml浓度范围内线性关系良好,方法回收率为88.6％～108.4％,日内、日间RSD小于5.3％.采用该法考察Beagle犬给予酮咯酸氨丁三醇鼻内喷雾剂（Sprix（R）） 31.25 mg后的药动学,主要参数分别为：cmax（4.72±1.06） μg/ml,AUC0→t（28.56±9.17） μg·ml-1·h,AUC0→∞（31.63±10.74）μg·ml-1·h,tmax（0.60±0.24）h,t1/2（9.48±7.43）h,MRT0→t（7.87±3.85）h.

A LC-MS/MS method was established for the determination of ketorolac in Beagle dog plasma. The detection of analyte and internal standard （glipizide） were conducted under positive ionization mode with an electrospray ionization （ESI） interface. A multiple reaction monitoring mode was chosen for the detection of m/z 256.4→m/z 105.1 （ketorolac） and m/z 446.4→m/z 321.1 （glipizide）. The calibration curve was linear in the concentration range of 0.05 - 10 μg/ml. The method recoveries were 88.6% - 108.4%. The intra- and inter-day RSDs were less than 5.3%. The pharmacokinetic characteristics in Beagle dogs after intranasal administration of 31.25 mg ketorolac tromethamine nasal spray （Sprix） was also investigated. The main pharmacokinetic parameters were as follows： cmax（4.72±1.06） μg/ml,AUC0→t（28.56±9.17） μg·ml-1·h,AUC0→∞（31.63±10.74）μg·ml-1·h,tmax（0.60±0.24）h,t1/2（9.48±7.43）h,MRT0→t（7.87±3.85）h.