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目的测定小鼠血浆中二甲双胍的浓度,并进行小鼠体内的药动学研究。方法小鼠灌胃给予盐酸二甲双胍(200、400、800mg/kg)并在0、0.33、0.67、1、2、3、4、6、8、10h共10个时间点采集血样(每个时间点小鼠3只),用HPLC法测定血浆样品中二甲双胍的浓度。结果二甲双胍在2～100mg/l的范围内呈线性关系;定量下限为2mg/L;低、中、高三种浓度加标回收率(%)分别为(93.4±2.7)、(87.3±1.9)、(86.4±1.7);日内RSD<5.2%,日间RSD<5.4%。二甲双胍在小鼠体内的血药浓度-时间曲线符合二室模型。主要药动学参数:三个剂量的AUC分别为(52.93±2.34)、(112.49±8.88)、(136.88±7.16)h/l;CL分别为(0.059±0.002)、(0.063±0.004)、(0.093±0.004)l/h;t1/2分别为(3.61±0.22)、(2.83±0.23)、(3.12±0.16)h;tmax均为0.67h;Cmax分别为(18.61±0.78)、(42.77±1.05)、(39.32±0.33)mg/l。结论该法简便、准确、灵敏,可用于二甲双胍药动学研究。
Objective To determine the concentration of metformin in the plasma of mice and study the pharmacokinetics in mice. Methods Mice were given metformin hydrochloride (200,400,800mg / kg) by gavage and blood samples were taken at 10 time points of 0, 0.33, 0.67, 1, 2, 3, 4, 6, 8 and 10h 3 mice), and the concentration of metformin in plasma samples was determined by HPLC. Results The metformin showed a linear relationship in the range of 2-100 mg / l with the lower limit of quantification being 2 mg / L. The recoveries (%) of low, medium and high concentrations were (93.4 ± 2.7) and (87.3 ± 1.9) (86.4 ± 1.7); intraday RSD <5.2%, daytime RSD <5.4%. The plasma concentration-time curve of metformin in mice conformed to the two-compartment model. The main pharmacokinetic parameters were as follows: the AUC of the three doses were (52.93 ± 2.34), (112.49 ± 8.88) and (136.88 ± 7.16) h / (3.93 ± 0.23) and (3.12 ± 0.16) h respectively; tmax was 0.67 h; Cmax were (18.61 ± 0.78) and (42.77 ± 1.05), (39.32 ± 0.33) mg / l. Conclusion The method is simple, accurate and sensitive and can be used for pharmacokinetics of metformin.