HPLC-MS/MS法测定人血浆中阿奇霉素浓度及药动学研究

Determination of azithromycin in human plasma by liquid chromatography-tandem mass spectrometry and its pharmacokinetic study

目的:建立测定人体内阿奇霉素血药浓度的HPLC-MS/MS方法,用于研究阿奇霉素分散片人体药动学。方法:应用建立的HPLC-MS/MS法测定人血浆中阿奇霉素浓度,以DAS软件进行房室模型拟合,计算主要药动学参数。结果:在选定的HPLC-MS/MS条件下阿奇霉素与内标及血浆杂质分离良好,在1.0～1000ng·mL-1的范围内线性良好。本方法回收率为88.7%～113.2%,日内和日间RSD均<15%。健康志愿者口服阿奇霉素分散片500mg后的药-时曲线符合二房室开放模型,主要药动学参数:t1/2α为(5.174±9·0)h;t1/2β为(31.4±22.7)h;ke为(0.022±0.008)h-1;Tmax为(1.70±0.66)h;Cmax为(549.8±242.9)ng·mL-1;k12为(0.199±0.262)h-1;k21为(0.217±0.463)h-1;AUC0～96为(3193±1166)ng·h·L-1;AUC0～∞为(3519±1333)ng·h·L-1。结论:本方法灵敏度高,无杂质干扰,结果准确。适用于阿奇霉素分散片人体内药动学研究。

Objective： To establish an HPLC-MS/MS method for determining azithromycin in human plasma and to study the pharmacokinetics of azithromycin dispersible table in healthy volunteers. Methods： The plasma concentration of azithromycin was determined by HPLC-MS/MS assay,and its pharmacokinetic parameters were calculated by DAS program. Results： The linear regressive curves were obtained in the range of 1.01000ng·mL^-1,and recoveries of azithromycin were 88.7%113.2% using this method. Within-day and between-day RSDs were less than 15% after a single oral dose of 500mg azithromycin dispersible tables in 20 healthy volunteers. The pharmacokinetic process fitted with the two compartment open models. The main pharmacokinetic parameters were： t1/2α（5.174±9.0）h;t1/2β（31.4±22.7）h;ke（0.022±0.008）h^-1;Tmax（1.70±0.66）h;Cmax（549.8±242.9）ng·mL^-1;k12（0.199±0.262）h^-1;k21（0.217±0.463）h^-1;AUC096（3193±1166）ng·h·L^-1;AUC0-∞（3519±1333）ng·h·L^-1,respectively. Conclusion： The HPLC-MS/MS method established in this study is accurate and sensitive with no endogenous interference,which can be adapted to pharmacokinetic study.