人全血中阿莫地喹的LC-MS/MS法测定及其药动学

Determination of Amodiaquine in Human Whole Blood by LC-MS/MS and Its Pharmacokinetics

建立了液相色谱-串联质谱法测定健康志愿者全血中的阿莫地喹（1）,并考察其在健康志愿者体内的药动学。以羟化氯喹为内标,使用Agilent Zorbax SB C18柱,乙腈∶20 mmol/L乙酸铵溶液（23∶77）为流动相;采用大气压力化学电离源（APCI）,多反应监测（MRM）模式,正离子检测,监测离子对为m/z 356.3→m/z 283.2（1）和m/z 336.0→m/z247.1（内标）。1在0.5~100 ng/ml浓度范围内线性关系良好,日内和日间RSD均小于10.0%,提取回收率大于70.4%。18名男性健康志愿者口服青蒿琥酯1盐酸盐片,主要药动学参数为cmax（25.9±4.7）ng/ml,tmax（1.1±0.3）h,t1/2（13.9±3.9）h,AUC0→t（294.5±42.8）ng·h·ml-1,AUC0→∞（310.3±45.0）ng·h·ml-1。

A LC-MS/MS method was established for the determination of amodiaquine （1） in whole blood from healthy volunteers, and its pharmacokinetics was studied. Hydroxychloroquine was used as the internal standard. An Agilent Zorbax SB C18 column was used, with the mobile phase of acetonitrile ： 20 mmol/L ammonium acetate solution （23 ： 77）, in the application of APCI source, in MRM and positive ionization mode, with the ion transitions of m/z 356.3→m/z 283.2 （1） and m/z 336.0→m/z 247.1 （internal standard）. The calibration curve of 1 was linear in the concentration range of 0.5 - 100 ng/ml. The intra- and inter-day RSDs were less than 10.0 %, and the extraction recovery was more than 70.4 %. The main pharmacokinetic parameters of 1 in 18 male healthy volunteers after oral administration of artesunate and 1 hydrochloride tablets were as follows： cmax（25.9±4.7）ng/ml,tmax（1.1±0.3）h,t1/2（13.9±3.9）h,AUC0→t（294.5±42.8）ng·h·ml-1,AUC0→∞（310.3±45.0）ng·h·ml-1