RP-HPLC测定巴洛沙星的人体血药浓度及生物等效性研究

 目的建立人血浆中巴洛沙星的HPLC测定法,研究巴洛沙星胶囊健康人体相对生物利用度。方法采用双周期自身交叉对照试验设计,20名健康志愿者口服受试巴洛沙星胶囊和参比巴洛沙星片各200 mg后采用HPLC测定血浆药物浓度。色谱柱为Lichmspher ODS(4.6 mm×25 cm,5μm)柱,流动相为水-乙腈-三乙胺-冰醋酸(78:22:1:1),紫外检测波长295 nm。结果巴洛沙星在0.03～4.0 mg·L^-1内线性关系良好(r=0.9997),提取回收率为85.37%～88.34%,相对回收率为98.45%～103.63%。受试、参比制剂的主要药动学参数如下:t_1/2(8.59±1.48)和(8.79±1.43)h,t_max (1.0±0.5)和(1.1±0.5)h,ρ_max(2.09±0.76)和(1.95±0.56)mg·L^-1,AUC_0-36h(15.15±2.98)和(16.77±11.36)mg·h·L^-1,AUC_0-∞(16.00±3.13)和(18.64±11.72)mg·h·L^-1,经对数转换根据两种制剂血药浓度-时间曲线下面积计算国产巴洛沙星胶囊剂相对生物利用度为(99.1±14.0)%。经方差分析及双单侧t检验,显示两制剂无显著性差异,具有生物等效性。结论此法简便、灵敏、准确、稳定,可用于体内药物分析,巴洛沙星胶囊和巴洛沙星片具有生物等效性。

Determination of Balofloxacin in Human Plasma by RP-HPLC and Its Application to Bioequivalence Research

OBJECTIVE To develop a HPLC method for the determination of balofloxacin in plasma and evaluate relative bioavailability of domestic balofloxacin capsule in healthy volunteers.METHODS A single oral dose of 200 mg balofloxacin domestic capsule and tablet was given to 20 health volunteers in a randomized crossover study.The balofloxacin concentrations in plasma were determined by HPLC method.The prepared sample was separated on the column of Lichrospher ODS(4.6 mm×25 cm,5μm), with the mobile phase consisting of H₂O-Acetonitrile-Triethylamine-HAc(78:22:1:1).The eluted peaks were detected by UV detector at 295 nm.RESULTS The calibration curve was linear in the range of 0.03%-4.0mg·L^-1(r=0.9997),the clean-up recovery of balofloxacin was 85.37%-88.34% and the analytical recovery was 98.45%-103.63%.The pharmacokinetic parameters of domestic capsules and tablets were as follows respectively:t_1/2(8.59±1.48)and(8.79±1.43)h,t_max(1.0±0.5)and (1.1±0.5)h,ρ_max(2.09±0.76)and(1.95±0.56)mg·L^-1,AUC_0-36h(15.15±2.98)and(16.77±11.36)mg·h·L^-1,AUC_0-∞(16.00±3.13)and(18.64±11.72)mg·h·L^-1.The relative bioavailability of domestic capsules was(99.1±14.0)%.The domestic capsules and tablets were bioequivalent.CONCLUSION The method was simple,sensitive,reliable and good enough to be used in pharmacokinetic study of balofloxacin.Two formulations in research are bioequivalent.