液相色谱-串联质谱法研究四物汤中芍药苷和芍药内酯苷在大鼠体内药代动力学

目的 建立LC-MS/MS法同时测定大鼠血浆中芍药苷和芍药内酯苷的含量，并研究灌胃给药四物汤后芍药苷和芍药内酯苷在大鼠体内的药代动力学性质。方法 大鼠血浆样品用乙腈沉淀蛋白；以甲醇和0.1%甲酸-水溶液为流动相梯度洗脱，用色谱柱Thermo Syncronis C18（2.1 mm×100 mm, 5 μm）进行分离；定量分析采用API 4000质谱仪的多反应监测扫描方式、负离子模式检测。将建立的方法应用于大鼠口服四物汤后芍药苷和芍药内酯苷的药代动力学研究。药代动力学参数由WinNonlin 5.2统计软件进行计算。结果 芍药苷和芍药内酯苷分别在2～1000 μg/L和1～1000 μg/L范围内线性关系良好，批内和批间精密度和准确度结果显示，批内、批间变异均小于15%，相对误差分别为-1.10%～2.74%和-4.02%～4.00%，方法学考察均符合要求。结论 所建方法专属性强，灵敏度高，可用于芍药苷和芍药内酯苷的药动学研究。

Pharmacokinetic study of paeoniflorin and albiflorin in Si-Wu decoction in rats by LC-MS/MS

Objective To establish a LC-MS/MS method for the determination of paeoniflorin and albiflorin in rat plasma and to investigate pharmacokinetic properties of paeoniflorin and albiflorin after oral administration of Si-Wu decoction to rats. Methods Plasma samples were treated by precipitating protein with acetonitrile and chromatographed by a Thermo Syncronis C18 column（2.1 mm×100 mm, 5 μm） with the mobile phase consisting of methanol and 0.1% formic acid solution. Quantitation was carried out by multiple-reaction monitoring in negative mode on an API 4000 LC-MS/MS system. Pharmacokinetic parameters were determined with WinNonlin 5.2 statistical software. Results Good linearity was found in the range of 2-1000 μg/L for paeoniflorin and 1-1000 μg/L for albiflorin, respectively. Intra-and inter-batch precisions were both less than 15%. The relative error was in the range of -1.10%-2.74% for paeoniflorin and -4.02%-4.00% for albiflorin, respectively. All items of method validation were in line with the requirements. Conclusion The established LC-MS/MS method is specific and sensitive, and can be applied to pharmacokinetic study of paeoniflorin and albiflorin.