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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
Objective: To establish a method for the determination of moclobemide in human plasma by RP-HPLC and to study the pharmacokinetics of moclobemide after multiple doses of Chinese male volunteers. Methods: The content of moclobemide in human plasma was determined by RP-HPLC. Plasma samples were extracted with dichloromethane under basic conditions (pH 11). The column was μ Bondapak ™ C18 (125, 10 μm, 3.9 mm × 150 mm). The mobile phase was acetonitrile: 0.06 7mol·L -1 potassium dihydrogen phosphate solution (1: 5, V / V, pH 2.6), 240nm detection. The internal standard is metoclopramide. Application of 3P97 program to fit pharmacokinetic parameters. Results: The calibration curve was linear in the range of 40-400 μg · L -1 (r = 0.9999). The recovery was between 99% and 103%. The intraday RSD was lower than 8.14%. The pharmacokinetic parameters of moclobemide were in accordance with one-compartment model. The main pharmacokinetic parameters Cmax were (3911 ± 14 2) μg · L- 1; Tmax was (1.4 2 ± 0.2) h; T1 / 2 (kel) was (2.6 ± 0.3) h; AUC0 2 4 was (2 2 5 83 ± 182 1) μg · h · L- 1; MRT was (4.76 ± 0.52) h; CL / F (s) is (2 1.2 ± 1.2) L · h-1. Conclusion: The method is rapid, accurate, sensitive and specific and can be applied to the determination of plasma concentration of moclobemide