高效液相色谱法测定吡美拉唑血药浓度及其药代动力学  

Determination of pymeprazole in human plasma by RP-HPLC and its pharmacokinetics

作　　者：孙黎[1] 苏克剑[1] 姚晓东[1] 茅益民 

机构地区：[1]上海交通大学医学院附属仁济医院临床药理研究室,上海200001 [2]上海交通大学医学院附属仁济医院消化科,上海200001

出　　处：《中国药理学与毒理学杂志》2012年第3期340-343,共4页Chinese Journal of Pharmacology and Toxicology

基　　金：国家科技部"重大新药创制"科技重大专项(2008ZX09312-007)~~

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25μg.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(29 089±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 col- umn 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 25 μg.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, C1/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.

关 键 词：吡美拉唑 高效液相色谱法 药代动力学 

分 类 号：R969.1[医药卫生—药理学] R975[医药卫生—药学]