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目的:建立测定大鼠血浆中大黄酸的固相萃取-高效液相色谱方法,研究大黄酸在大鼠体内的药动学规律。方法:单次给予SD大鼠不同剂量的大黄酸,于不同时间点采集大鼠血浆。以固相萃取法处理血浆样品,用HPLC内标法测定血药浓度,色谱柱为Venusil XBP C18(L)(4.6 mm×250 mm,5μm),流动相为甲醇-0.1%磷酸水(75∶25),柱温为30℃,检测波长254 nm,以DAS2.0软件拟合计算药动学参数。结果:大黄酸的血药浓度在0.019 2～11.72 mg.L-1线性关系良好(R2=0.999 1),检测限为0.009 6 mg.L-1,定量限为0.019 2 mg.L-1,提取回收率均大于80%,日内、日间精密度RSD均小于6%。结论:大鼠灌胃给药大黄酸血药浓度-时间曲线呈二室模型。该法操作简便、快速、灵敏,适用于大黄酸在大鼠体内的药物动力学研究。
OBJECTIVE: To establish a method for the determination of rhein in rat plasma by high performance liquid chromatography (HPLC) and study the pharmacokinetics of rhein in rats. Methods: The rats were given single dose of rhein at different dosages and plasma was collected at different time points. The plasma samples were processed by solid-phase extraction (SPE), and the plasma concentration was determined by HPLC internal standard method. The chromatographic column was Venusil XBP C18 (L) (4.6 mm × 250 mm, 5 μm) 25). The column temperature was 30 ℃ and the detection wavelength was 254 nm. The pharmacokinetic parameters were calculated by software DAS2.0. Results: Rhein had a good linearity of 0.019 2 ~ 11.72 mg.L-1 (R2 = 0.999 1), the limit of detection was 0.009 6 mg.L-1, the limit of quantification was 0.019 2 mg.L-1, The recovery rates were more than 80%. The RSDs of intra-day and inter-day precision were less than 6%. Conclusion: The concentration-time curve of rhein in rats administered by gavage is a two-compartment model. The method is simple, rapid, sensitive and suitable for the pharmacokinetics of rhein in rats.