高效液相色谱法测定吡美拉唑血药浓度及其药代动力学

摘要

目的 建立测定吡美拉唑血药浓度的高效液相色谱(HPLC)方法,并初步考察其在人体内的药代动力学特性.方法 受试者口服吡美拉唑10 mg后,分别于给药前,给药后0.5,1,1.5,2,4,8,12,21,36,48,60和72 h采集血样,通过HPLC吡美拉唑的血药浓度,并应用3P87软件拟合并计算药代动力学参数.结果 吡美拉唑的线性范围为25 ～4000μg·L-1,最低检测浓度为25 μ8·L-1,回收率95.2％ ～107.7％,日内精密度均＜6.9％,日间精密度＜10.2％.吡美拉唑的主要药代动力学参数:t1/2为(22.58±1.59)h,AUC0-72为(29089±8886) μg·h·L-1,Cl/F为(338.9±114.0)L·h-1,tmax为(2.67±1.54)h,cmax为(1585±469)μg·L-1.结论 吡美拉唑在人体内吸收快,半衰期较长,有效作用时间长,疗效好.%OBJECTIVE To establish a high performance liquid chromatography (HPLC) method for pymeprazole in humans, and to explore its pharmacokinetics. METHODS HPLC column was Diamond C18(5 μm, 250 mm ×4. 6 mm) column, the mobile phase was 0. 05 mol·L-1 phosphatic buffer (pH =6.50)-acetonitrile (64:36, V/V) , flow rate was 1.0 ml-min"1, and UV detection wavelength was set at 305 nm. Subjects were given pymeprazole 10 mg (po) before blood samples were collected at 0, 0. 5 , 1, 1.5,2,4,8, 12, 24, 36, 48, 60 and 72 h after administration. Concentrations of pymeprazole in plasma were determined by HPLC, and parameters were calculated with 3P87 software. RESULTS The calibration curve of pymeprazole in plasma samples was linear over the range of 25 - 4000 μg · L-1 ( r = 0. 99998). The lower limit of quantification for pymeprazole in plasma was 25μg·L-1. The recovery of the method was from 95. 2% to 107. 7%. The intra-day RSD and inter-day RSD were less than 6. 9% and 10. 2% , respectively. The main pharmacokinetic parameters of pymeprazole were t1/2 (22. 58 ± 1. 59) h, AUC0_72 (29 089 ± 8886)μg·h·L-1 CI/F (338.9 ± 114. 0)L·h-1, tmax(2.67 ±1.54)h, and Cmax was (1585 ± 469)μg·L-1. CONCLUSIONS HPLC method is simple, quick, sensitive and accurate. Pymeprazole is rapidly absorbed, and its t1/2 is longer than that of other proton inhibitors in subjects.