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目的建立测定大鼠血浆中1,8-二川芎嗪基大黄酸浓度的HPLC方法,并对大鼠尾静脉注射给药1,8-二川芎嗪基大黄酸后,研究其在大鼠体内的药代动力学。方法采用大黄素为内标,血浆样品用甲醇沉淀蛋白后进行HPLC分析,流动相为甲醇-0.1%甲酸水(78∶22,V/V),流速为1.0m L·min-1,检测波长为275 nm。大鼠单剂量静脉注射2、4、8 mg·kg-11,8-二川芎嗪基大黄酸后,测定给药后不同时间点大鼠血浆中1,8-二川芎嗪基大黄酸的浓度,并对其血药浓度-时间曲线采用DAS 2.1软件拟合,计算药动学参数。结果 1,8-二川芎嗪基大黄酸在0.05-10.00 mg·L-1血浆浓度范围内线性关系良好(r=0.996 2),定量下限为0.05mg·L-1,提取回收率均大于88%,日内和日间差异RSD均小于6%,方法学考察均符合要求。1,8-二川芎嗪基大黄酸按2、4和8 mg·kg-1静脉注射给药后,在大鼠体内的T1/2分别为(68.35±1.36)、(69.32±2.21)、(69.32±2.03)min,AUC0-t分别为(101.03±24.9),(144.79±3.29),(231.92±19.30)min·mg·L-1。结论本实验所建立的HPLC方法操作简便、快速、专属性强,可用于1,8-二川芎嗪基大黄酸血药浓度分析及其药代动力学研究。
OBJECTIVE To establish an HPLC method for the determination of 1,8-Ligustrazine-based rhein in rat plasma and to study the effects of 1,8-D-toltazine-based rhein on rat tail vein injection Pharmacokinetics. Methods Emodin was used as an internal standard. The plasma samples were precipitated with methanol and analyzed by HPLC. The mobile phase consisted of methanol-0.1% formic acid water (78:22, V / V) and the flow rate was 1.0 m L · min-1. 275 nm. After single-dose intravenous injection of 2,4,8 mg · kg-11,8-trimethoprim-L-rhein, the concentrations of 1,8-Ligustrazine in rat plasma at different time points after administration , And its plasma concentration - time curve using DAS 2.1 software fitting, calculation of pharmacokinetic parameters. Results The linear relationship was found between the concentrations of 1,8-Ligustrazine and rhein in the concentration range of 0.05-10.00 mg · L-1 (r = 0.996 2), the lower limit of quantitation was 0.05 mg · L-1, and the recoveries were both higher than 88 %, Intra-day and inter-day difference RSD were less than 6%, methodological inspection met the requirements. Twenty-two ligustrazine-based rhein were intravenously administrated at 2, 4 and 8 mg · kg-1, respectively, with T1 / 2 in rats being (68.35 ± 1.36), (69.32 ± 2.21) and 69.32 ± 2.03) min and AUC0-t were (101.03 ± 24.9), (144.79 ± 3.29) and (231.92 ± 19.30) mg · L-1, respectively. Conclusion The HPLC method established in this experiment is simple, rapid and specific. It can be used for the analysis of 1,8-Ligustrazine-based rhein concentration and its pharmacokinetics.