液相色谱-电喷雾离子化-质谱联用法测定大鼠血浆中柴胡皂苷a浓度及其药代动力学

Pharmacokinetic study of saikosaponin a in rat plasma by LC-ESI-MS

目的建立测定柴胡皂苷a血浆药物浓度的液相色谱-电喷雾离子化-质谱联用的分析方法(LC-ESI-MS),探讨其在大鼠体内的药代动力学研究中的应用。方法SD大鼠12只,随机分为2组,分别单剂量静注(5mg·kg-1)和灌胃(50mg·kg-1)柴胡皂苷a,用LC-MS法测定给药后大鼠血浆中药物浓度,利用DAS软件拟合并计算其药代动力学参数。结果柴胡皂苷a的血药浓度在0.025～5mg·mL-1范围内线性关系良好,最低检测限为25μg.L-1,以质控样品计算,在各浓度水平下,此法的回收率均大于80%,日间和日内精密度小于10%,符合生物样品分析要求。大鼠单剂量静注柴胡皂苷a5mg·kg-1后,血药浓度-时间曲线呈二室模型。主要药动学参数Tmax,Cmax,AUC0-t,T12β,CL,Vd分别为:5min,1907μg.L-1,64370mg.h-1.L-1,100.6min,0.0867L·min-1.kg-1,21.89L.kg-1。结论该方法操作简便、快速、灵敏、专属性强,可用于柴胡皂苷a的体内大批量样品定量分析及药代动力学研究。

Aim To establish an LC-ESI-MS method for determination of saikosaponin a and investigate its application to pharmacokinetic study in rats. Methods 12 rats were given 5 or 50 mg · kg^-1 saikosaponin a via iv or ig. Drug plasma concentration was determined by LC-ESI-MS and pharmacokinetic parameters were e- valuated by DAS Software. Results Calibration curve was linear between 0. 025 - 5 mg · kg^-1and LOQ was 25 μg · kg^-1, the recoveries of saikosaponin a from plasma over than 80% , and RSD of inter-day and intra-day assay was limited in 10%. After iv administra-tion of 5 mg · kg^-1 saikosaponin a, the pharmacokinetic parameters of T C AUC0,, Tmax, CL and Vd were 5 rain, 1 907 μg· L^-1,64370 mg·h^-1 · L^-1, 100.6 rain,0. 0867 L · min^-1 · kg^-1,21.89 L · kg^-1 respectively. Conclusion The above-mentioned method is sensitive and specific, and suitable for phannacokinetie studies of saikosaponin a in rats.