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目的建立大鼠血浆中没食子酸的高效液相测定方法;研究大鼠灌胃与静脉给药后没食子酸的药物动力学过程及生物利用度。方法分别灌胃和静脉给予大鼠没食子酸,不同时间点采血,样品经甲醇沉淀蛋白后,采用Phenomenex C18(250 mm×4.6 mm,4μm)色谱柱,甲醇-体积分数为0.5%的冰醋酸水溶液(体积比为7∶93)为流动相,流速为1.0 mL.min-1,检测波长为272 nm,以对乙酰氨基酚为内标测定血浆中没食子酸的浓度。应用DAS 2.0软件计算药物动力学参数。结果大鼠灌胃给药后t1/2α为46.57 min,t1/2β为56.54 min,tmax为66.00 min,ρmax为3.96 mg.L-1,AUC0~t为396.5 mg.min.L-1;静脉给药后t1/2α为9.90 min,t1/2β为78.88 min,AUC0~t为461.9 mg.min.L-1。结论大鼠灌胃和静脉给予没食子酸后,其药-时过程均符合二室模型,绝对生物利用度为42.9%。
Objective To establish a HPLC method for the determination of gallic acid in rat plasma and study the pharmacokinetics and bioavailability of gallic acid after intragastric and intravenous administration in rats. Methods Gallic acid was intragastrically and intravenously administered to rats. At different time points, blood was collected. After the sample was precipitated with methanol, Phenomenex C18 (250 mm×4.6 mm, 4 μm) column was used. The methanol-aqueous 0.5% glacial acetic acid solution was used. The volume ratio of 7:93 was the mobile phase, the flow rate was 1.0 mL.min-1, the detection wavelength was 272 nm, and the concentration of gallic acid in plasma was determined using acetaminophen as the internal standard. DAS 2.0 software was used to calculate pharmacokinetic parameters. Results After intragastric administration, t1/2α was 46.57 min, t1/2β was 56.54 min, tmax was 66.00 min, ρmax was 3.96 mg.L-1, and AUC0~t was 396.5 mg.min.L-1. After administration, t1/2α was 9.90 minutes, t1/2β was 78.88 minutes, and AUC0-t was 461.9 mg.min.L-1. Conclusion After gavage and intravenous administration of gallic acid in rats, the drug-time course was consistent with the two-compartment model, and the absolute bioavailability was 42.9%.