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目的建立测定大鼠血浆中甘草甜素反相高效液相色谱法(HPLC),并研究脾虚大鼠灌胃甘草甜素的药物动力学(PK)。方法以联苯为内标,流动相为:甲醇一水一醋酸(80:19:1,v/v),固定相为 ODS-3色谱柱(150 mm×4.6 mm,5μm),检测波长:250nm,流速:1.0 mL/min。Wistar大鼠利血中每日肌肉注射0.3 mg/kg,连续14 d造成脾虚模型。空腹14 h,灌胃甘草甜素并分别在5、10、20、30、0、120和 180 min取血,获得血浆,测定血药浓度一时间数据,以 3P87软件包进行拟合。结果本方法最低检测限为 2 ng,日间和日内 CV%均< 10%,回收率在 96.20%和 103,21%之间,在 40.8~ 1467. 8 μg/mL范围内符合良好的线性关系。PK属于开放性二室模型。结论本法简便、快速、灵敏而准确,适用于大鼠血浆GL的测定。
Objective To establish a reversed-phase high performance liquid chromatography (HPLC) method for the determination of glycyrrhizin in rat plasma and to study the pharmacokinetics (PK) of glycyrrhizin administered to the spleen asthenia rats. Methods Biphenyl was used as the internal standard. The mobile phase consisted of methanol-water-acetic acid (80:19:1, v/v) and the stationary phase was ODS-3 column (150 mm×4.6 mm, 5 μm). Wavelength: 250 nm, flow rate: 1.0 mL/min. Wistar rats received intramuscular injection of 0.3 mg/kg intramuscularly daily for 14 days to cause a spleen deficiency model. On the fasting 14 h, glycyrrhizin was intragastrically administered and blood was taken at 5, 10, 20, 30, 0, 120 and 180 min respectively to obtain plasma. The plasma concentration was measured for one time and was fitted with the 3P87 software package. Results The minimum detection limit of the method was 2 ng, the intra- and intra-day CV% were both less than 10%, and the recoveries were between 96.20% and 103.21%, ranging from 40.8 to 1467. A good linear relationship was observed in the 8 μg/mL range. PK is an open two-room model. Conclusion This method is simple, rapid, sensitive and accurate, suitable for the determination of plasma GL in rats.