液相色谱法测定吗氯贝胺及其多剂量口服后在人体的药动学(英文)

目的 :建立人血浆中吗氯贝胺的反相高效液相色谱检测方法 ,并研究中国健康男性志愿者多剂量口服吗氯贝胺后的药动学特征。方法 :采用反相高效液相色谱法测定人血浆中吗氯贝胺含量。血浆样品在碱性条件下 (pH 11)用二氯甲烷提取处理。色谱柱为 μ BondapakTM C18(12 5 ,10 μm ,3.9mm× 15 0mm)。流动相为乙腈 :0 .0 6 7mol·L- 1磷酸二氢钾溶液 (1∶5 ,V/V ,pH 2 .6 ) ,2 4 0nm检测。内标为甲氧氯普胺。应用 3P97程序拟合药动学参数。结果 :吗氯贝胺在 4 0～ 4 0 0 0 μg·L- 1范围内线性关系良好 (r =0 .9999) ,方法回收率在 99%～10 3%之间 ,日内日间RSD小于 8.14 %。吗氯贝胺血药浓度 时间曲线符合一室模型 ,主要稳态药动学参数Cmax为 (3911± 14 2 ) μg·L- 1;Tmax为 (1.4 2± 0 .2 0 )h ;T1/2 (kel) 为 (2 .6± 0 .3)h ;AUC0 2 4 为(2 2 5 83± 182 1) μg·h·L- 1;MRT为 (4.76± 0 .2 5 )h ;CL/F(s) 为 (2 1.2± 1.2 )L·h- 1。结论 :该方法快速、准确、灵敏度高、专属性强 ,可应用于吗氯贝胺的血药浓度测定

Determination of moclobemide in human plasma by high pressure liquid chromatography and its pharmacokinetics after multiple oral dosing in healthy volunteers

AIM: To establish a reversed-phase high performance liquid chromatography method for the determination of moclobemide in human plasma and investigate the pharmacokinetic of moclobemide after multiple oral dosing in healthy Chinese male volunteers. METHODS: The concentrations of moclobemide in plasma were determined by the reversedphase high performance liquid chromatography. Moclobemide and internal standard ( metoclopramide )were extracted from basified plasma (pH 11) with dichloromethane and separated on μ-BondapakTM C18column (125A, 10 μm, 3.9 mm × 150 mm) with a mobile phase consisting of acetonitrile and 0. 067V/V, pH 2.6). The detection wavelength was 240nm. The partial pharmacokinetic parameters were calculated with 3P97 pharmacokinetic program.RESULTS: The linearity was excellent over the methodological recoveries of moclobemide were from 99 % to 103 %. The within-day and between-days relative standard deviations were less than 8.14 %.The concentration-time profile was best fitted with an one-compartment model with first-order absorption.The steady-state pharmacokinetic parameters of moclobemide tablets after multiple oral dosing were as (1.42± 0. 20) h, T1/2(kel) was (2. 6 ± 0. 3) h,h-1, respectively. CONCLUSION: The elaborated HPLC method is sensitive, precise, and selective, and can be used in measurement of moclobemide in plasma.