LC-MS/MS法测定人血浆中安妥沙星的浓度及盐酸安妥沙星片在健康人体的药代动力学研究

目的用LC-MS/MS法测定人血浆中安妥沙星的浓度,并研究口服盐酸安妥沙星片后安妥沙星在人体内的药代动力学特征。方法血浆样本经乙腈沉淀蛋白后,以奥硝唑为内标。色谱柱:Agilent Poroshell 120 SB-C18(2.1 mm×50mm,2.7μm),流动相:乙腈-5 mmol·L^-1甲酸铵(含0.1%甲酸)=12∶88,流速:0.4 m L·min^-1。12名健康受试者单剂量空腹口服盐酸安妥沙星400 mg,采集不同时间点血样,用LC-MS/MS法测定人血浆中安妥沙星的浓度,并用DAS2.1.1和Excel 2003软件计算主要药代动力学参数。结果安妥沙星在0.01~15.00μg·m L^-1内线性良好,准确度、批内和批间精密度均小于15%,在测定过程中稳定性符合要求。安妥沙星单次给药400 mg后的主要药代动力学参数:Cmax为(3.57±0.54)μg·m L^-1,tmax为(2.25±0.92)h,t1/2为(11.76±1.64)h,AUC0-t为(60.38±7.47)μg·m L^-1·h。结论该方法可用于测定人血浆中安妥沙星的浓度,并可用于研究盐酸安妥沙星片在人体内的药代动力学特征。

Determination the concentration of antofloxacin in human plasma by LC-MS/MS and its application in the pharmacokinetic study of antofloxacin hydrochloride

LI Hui -juan1＇2, SUN Lu -ning, ZHANG Hong - wen , YING Yu - wen1 , JIAO Hui - wen , MA Yun - su1, XIE Li -jun, CHEN Juan1, OU Ning(1. Research Division of Clinical Pharmacology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China; 2. Drug Clinical Trial Institution Office, The People＇s Hospital of Guangxi Zhuang Autonomous Region, Nanning 530021, Chin)