HPLC-MS/MS研究阿奇霉素片人体药动学

 目的建立HPLC-MS/MS检测体内阿奇霉素血药浓度,并用于研究阿奇霉素片人体药动学。方法应用建立的HPLC-MS/MS方法测定人血清中阿奇霉素的浓度,并通过PKs软件进行房室模型拟合,计算主要药动学参数。结果阿奇霉素的线性范围为3.33～833μg·L^-1,方法回收率为100%～115%,日内、日间RSD值均小于6%,人po阿奇霉素500 mg后的药-时曲线均符合二房室开放模型,其主要药动学参数t_1/2α为(2.93±3.38)h,t_1/2β为(36.24±8.34)h,t_1/2ka为(0.61±0.34)h,ρ_max为(415.9±114.4)μg·L^-1,t_max为(1.812±0.650)h,AUC_0-t为(6 937±1 626)μg·h·L^-1,CL/F为(0.076±0.018 2)L·h^-1,Vd/F为(3.976±1.413)L,t_lag为(0.349±0.173)h,k₁₀为(0.110±0.039)h^-1,k₂₁为(0.067±0.025)h^-1,k₁₂为(0.223±0.109)h^-1。结论该法简便、灵敏、特异,适用于阿奇霉素片人体药动学研究。

Pharmacokinetics Study of Azithromycin Tablets in Health Volunteers by HPLC-MS/MS

OBJECTIVE To establish HPLC-MS/MS method for the determination of azithromycin in human serum,study pharmacokinetics of azithromycin in healthy volunteers.METHODS azithromycin in serum were determined by LC-MS/MS and the pharmacokinetic parameters were calculated by PKs program.RESULTS The linear regressive curves were obtainedinthe range of 3.33～833μg·L^-1.Re-coveries usingthe method of azithromycin was 100 %～115 %.The within-day and betweenday RSDs were lessthan 6 %.After oral adminationof azithromycintablets in 18 healthy volunteers,the pharmacokinetive process was fittedtothe two-compartment mode,the main pharmacoki-netics parameters were :t_1/2α(2.93±3.38)h,t_1/2β(36.24±8.34)h,t_1/2ka(0.61±0.34)h,ρ_max(415.9±114.4)ng·mL^-1,t_max(1.812±0.650)h,AUC_0-t(6937±1626) μg·h·mL^-1,CL/F(0.076±0.0182) L·h^-1,Vd/F(3.976±1.413) L,t_lag(0.349±0.173)h,k₁₀(0.110±0.039)h^-1,k₂₁(0.067±0.025)h^-1 and k₁₂(0.223±0.109)h^-1.CONCLUSION HPLC-MS/MS method established in thisstudyis simple,sensitive with good accuracy and precision,which can be adaptedto pharmacokinetics study.