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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 the determination of azithromycin in human body for the study of human pharmacokinetics of azithromycin dispersible tablets. Methods: The concentration of azithromycin in human plasma was determined by HPLC-MS / MS method. The main pharmacokinetic parameters were calculated by DAS software. Results: The azithromycin was separated from the internal standard and plasma impurities under the selected HPLC-MS / MS conditions. The linearity was good in the range of 1.0 ~ 1000 ng · mL-1. The recovery rate of this method was 88.7% ~ 113.2%, RSD both within and outside the day were <15%. The drug-time curve of oral administration of 500 mg azithromycin dispersible tablets in healthy volunteers was in accordance with the two-compartment open model. The main pharmacokinetic parameters were t1 / 2α (5.174 ± 9.0) h, t1 / 2β (31.4 ± 22.7) h, ke was (0.022 ± 0.008) h-1, Tmax was (1.70 ± 0.66) h, Cmax was (549.8 ± 242.9) ng · mL-1, k12 was (0.199 ± 0.262) h-1 and k21 was (0.217 ± 0.463) ) h-1; AUC0 ~ 96 was (3193 ± 1166) ng · h · L-1; AUC0 ~ ∞ was (3519 ± 1333) ng · h · L-1. Conclusion: The method has high sensitivity, no impurity interference and accurate results. Pharmacokinetics for azithromycin dispersible tablets in human body.