UPLC法测定大鼠血浆中藤黄酸葡萄糖酯及其药代动力学研究

目的: 建立测定大鼠血浆中藤黄酸葡萄糖酯浓度的UPLC方法,并探讨其在大鼠体内的药代动力学。方法: 以新藤黄酸为内标,建立大鼠血浆中藤黄酸葡萄糖酯的UPLC测定方法。采用该方法测定大鼠单剂量静脉注射2、 4 、8 mg/kg 藤黄酸葡萄糖酯后,不同时间点大鼠血浆中的藤黄酸葡萄糖酯的浓度,对其血药浓度-时间采用DAS 2.1 软件拟合,计算药动学参数。结果: 血浆中藤黄酸葡萄糖酯在 0.05～14.0 mg/L 浓度范围内线性关系良好(r=0.9999) ,定量下限为 0.05 mg/L,提取回收率均大于87%,其日内日间RSD均小于10% ,藤黄酸葡萄糖酯按2、4和 8 mg/kg 静脉给药后,在大鼠体内的t_1/2分别为(16.66±1.56)、(16.81±2.21) 和(17.88±2.05) min,AUC_0-t 分别为(12.92±13.14)、(37.3±18.58) 和 (68.22±20.91) min·mg·L^-1。结论: 所建立的UPLC方法操作简便、快速、专属性强,能满足藤黄酸葡萄糖酯在大鼠体内的药代动力学研究。

Determination of glyco-gambogic acid and its pharmacokinetics in rat plasma by UPLC

AIM: To develop an UPLC method for the determination of plasma concentration of glyco-gambogic acid (Glyco-GA) and study the pharmacokinetics of Glyco-GA in rat plasma.METHODS: An UPLC method was established for the determination of Glyco-GA in rat plasma and using Gambogenic acid as the internal standard. The plasma concentration of Glyco-GA in rats was determined by UPLC after intravenous administration of Glyco-GA at a does of 2, 4 and 8 mg/kg, and the pharmacokinetic parameters were calculated by DAS 2.1.RESULTS: Calibration curve was linear over the range of 0.05-14.0 mg/L(r=0.9999). The lower limit of quantification was 0.05 mg/L. The extraction recoveries were higher than 87%. The intra-day and inter-day precision(RSD%) was lower than 10%, respectively. This method was applied to a pharmacokinetic study after i.v. administration of Glyco-GA in rats at a does of 2, 4 and 8 mg/kg. The T_1/2 of Glyco-GA was (16.66±1.56), (16.81±2.21) and (17.88±2.05) min, the AUC_0-t was (12.92±13.14), (37.3±18.58) and (68.22±20.91) min·mg·L^-1, respectively.CONCLUSION: A simple,rapid and specific UPLC method for the analysis of Glyco-GA was successfully developed and applied to a pharmacokinetic study of Glyco-GA in rat plasma.