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

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

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DAS2.1 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t1/2分别为（16.66±1.56）、（16.81±2.21） 和（17.88±2.05） min，AUC0-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。

AIM： To develop an UPLC method for the determination of plasma concentration of gly- co-gambogic acid （Glyco-GA） and study the phar- macokinetics of Glyco-GA in rat plasma. METH- ODS： An UPLC method was established for the de- termination of Glyco-GA in rat plasma and using Gambogenic acid as the internal standard. The plas- ma concentration of Glyco-GA in rats was deter- mined 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 in- tra-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 T1/2 of Glyco-GA was （ 16.66 ± 1.56）, （ 16.81 ±2.21） and （17.88 ±2.05） rain, the AUG_0-t was （12.92 ±13.14）, （37.3 ±18.58） and （68.22 ± 20.91 ） min · mg · L^-1, respectively. CONCLU- SION： A simple, rapid and specific UPLC method for the analysis of Glyco-GA was successfully devel- oped and applied to a pharmacokinetic study of Gly- co-GA in rat plasma.