格列吡嗪血药浓度测定及中国健康人体药物动力学研究

Determination of glipizide in human plasma by RP-HPLC and its pharmacokinetics in Chinese healthy subjects

目的建立反相高效液相色谱法测定人血浆中格列吡嗪浓度的方法,以及研究格列吡嗪片在中国健康人体的药物动力学。方法以KiomasalC18(4.6mm×125mm,5μm)为分析柱,乙腈0.05mol·L-1磷酸二氢钾缓冲液(38∶62,v/v)为流动相,流速为1.0mL·min-1,二极管阵列检测器(DAD)检测波长为225nm,艾司唑仑为内标,测定血浆中格列吡嗪的浓度。结果在浓度20.4～2040ng·mL-1,格列吡嗪和内标峰面积比值与浓度呈良好的线性关系(r=0.9993)。格列吡嗪高、中、低3个浓度的平均回收率分别为(105.2±4.4)%、(92.9±5.0)%、(109.4±8.4)%;日内、日间RSD均小于10%。药物动力学研究表明,格列吡嗪体内过程符合一室模型,体内药物tmax、cmax、t1/2(Ke)、AUC0～24分别为(1.6±0.3)h、(728.5±229.7)ng·mL-1、(3.3±0.9)h、(4130.5±1383.0)ng·h·mL-1。结论方法简便、快速准确、重现性好,可用于格列吡嗪的药物动力学研究。

OBJECTIVE To establish an RP-HPLC method for the determination of glipizide in human plasma and investigate the pharmacokinetics of glipizide in Chinese healthy subjects.METHODS Serum concentration of glipizede and internal standard(estazolam) were determined by DAD at UV 225 nm. Using Kiomasal C_ 18(4.6 mm×125 mm,5 μm)analytical column, the mobile phase consisted of acetonitrile - 0.05 mol·L~ -1 potassium dihydrogen phosphate (38∶62 ,v/v) at the flow rate of 1.0 mL· min~ -1.RESULTS The linear ranges of glipizide were 20.4～204 0 ng· mL~ -1 (r=0.999 3). The average recoveries for the three concentrations of glipizide were (105.2±4.4)%,(92.9±5.0)%,and(109.4±8.4)%,respectively. The RSD of within-day and between-day was less than 10%. The pharmacokinetics of glipizide fit an one-compartment model. The t_ max, c_ max, t_ 1/2(Ke),and AUC_ 0~24 of glipizide were (1.6±0.3) h, [KG-*4](728.5±229.7)ng·mL~ -1, (3.3±0.9) h,and (4 130.5±1 383.0)ng·h·mL~ -1, respectively.CONCLUSIONS The method is convenient,fast, reproducible and suitable for pharmacokinetic study of glipizide.