泮托拉唑钠对映体在犬体内的药代动力学研究

目的: 建立采用HPLC-MS/MS测定血浆中泮托拉唑钠对映体的方法,研究泮托拉唑钠对映体在犬体内的药代动力学特征.方法: 血浆用乙腈沉淀蛋白,非那西丁做内标.色谱条件:采用多糖衍生物共价键合手性柱,以乙腈-水(28:72,v/v)为流动相;质谱条件:离子化方式为电喷雾-正离子,多重反应监测模式.用此方法测定了犬静注给予消旋体泮托拉唑钠1.6 mg·kg^-1后6 h内对映体的血浆药物浓度.结果: 该法的线性范围为1.5~1500 ng·mL^-1,提取回收率范围为90.9%~105.8%,日内及日间精密度在0.4%~6.8%范围内.血药浓度-时间数据经DAS 2.1.1程序处理,泮托拉唑钠左旋体与右旋体的主要药代动力学参数分别为:C_max(2886.07±719.22)、(2816.06±917.91)μg·L^-1;AUC_(0-6h)(2228.78±551.03),(2360.56±622.59)μg·L^-1·h;T_1/2(0.46±0.08)、(0.51±0.14)h.结论: 试验结果表明,泮托拉唑钠在Beagle犬体内代谢迅速,泮托拉唑钠中左旋体与右旋体AUC_{(0-6 h)}的比值是0.94,未发现左旋体与右旋体之间存在明显的相互转化.

Objective: To establish a method to determine pantoprazole sodium(Pan-Na)enantiomers in plasma and study its pharmacokinetics. Methods: The plasma protein was precipitated by acetonitrile with phenacetin as the internal standard.Liquid chromatography conditions were as follows.The polysaccharide derivative covalent bonding chiral column was used with the mobile phase consisting of acetonitrile-water(28:72).Mass spectrometry conditions were set as follows.The ionization way was electrospray ionization(ESI)at a positive ion mode.The pattern was multiple reaction monitoring.The plasma concentration of enantiomers was determined under these conditions within six hours after intravenous administration of racemic Pan-Na in dogs. Results: The linear range was 1.5-1500 ng·mL^-1.The recovery was 90.9%-105.8%.The intra- and inter-day precisions were 0.4%-6.8%.Concentration-time data were processed by DAS 2.1.1. Maximal plasma concentration(C_max)for l-Pan-Na was(2886.07±719.22)μg·L^-1, for d-Pan-Na was(2816.06±917.91)μg·L^-1.Area under blood concentration-time(AUC_{(0-6 h)})for l-Pan-Na was(2228.78±551.03)μg·L^-1·h, for d-Pan-Na was(2360.56±622.59)μg·L^-1·h.The biological half-life(T_1/2)for l-Pan-Na was(0.46±0.08)h, for d-Pan-Na was(0.51±0.14)h. Conclusion: The results showed that Pan-Na was metabolized rapidly in dogs.The AUC_{(0-6 h)} ratio of l-Pan-Na and d-Pan-Na in Pan-Na was 0.94.There was not obvious reciprocal transformation of l-Pan-Na and d-Pan-Na.