高效液相色谱法测定人血浆中丁咯地尔含量及药动学研究

 目的建立人血浆中丁咯地尔含量的高效液相色谱法，并用该法研究盐酸丁咯地尔片在健康人体内的药动学。方法色谱柱为ALLTECH C₁₈(5μm,200 mm×4.6 mm)，流动相为甲醇-水-三乙胺(60∶40∶0.4)，用冰醋酸调节pH 6.5，以地西泮为内标，紫外检测波长275 nm。结果浓度在0.02～4.00 mg·L^-1范围内对样品峰面积与内标峰面积比呈良好线性关系，其相关系数r=0.9995。方法平均回收率93.3%，日内、日间相对误差＜12.0%。应用该法研究了12例健康志愿者po300 mg盐酸丁咯地尔片后的药动学；其体内过程符合一室模型,t_max为(1.58±0.29)h,c_max为(2.39±0.48) mg·L^-1,AUC_0～24为(17.68±4.66) mg·h·L^-1。结论此法简便、快速，适用于药物分析，其药动学数据可为临床合理用药、新药研制及剂型改进提供理论依据。

Studies on determination of buflomedil in human plasma and its pharmacokinetics by high-performance liquid chromatography

OBJECTIVE A reversed phase high performance liquid chromatographic method was established for the determination of buflomedil in human plasma and was applied to the pharmacokinetic study of buflomedil in 12 healthy volunteers.METHOD The chromatographic separation was achieved on a Alltech C₁₈(column (200 mm×4.6 mm,5μm),with methanol-H₂O -triethylamine(60∶40∶0.4 pH 6.5)as the mobile phase.The detection wavelength was at 275 nm.The internal standard was Diazepam. After alkaline with 2 mol·L^-1NaOH,the plasma was extracted with n hexane dichloromethane(3∶1).RESULTS A good linearity was obtained from 0.02 mg·L^-1to 4.00 mg·L^-1of buflomedil in human plasma with a correlation coefficient of 0.9995.The detection limit was 0.01 mg·L^-1.The extraction recovery was more than 93%. The within day and between day RSD were less than 12.0%.The pharmacokinetic analysis of buflomedil hydrochloride in 12 healthy volunteers after oral administration of 300 mg was studied.It was found to be fitted to a one compartment open model and its pharmacokinetic parameters were as follow:t_max(1.58±0.29)h,c_max(2.39±0.48) mg·L^-1,AUC_0～24(17.68±4.66) mg·h·L^-1,respectively.CONCLUSION The pharmacokinetics of buflomedil in human provided a useful index for clinical trial.