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  

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

作　　者：李汇涓 孙鲁宁[1] 张宏文 应玉雯 焦慧文 马云苏 谢利军 陈娟 欧宁 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)

机构地区：[1]南京医科大学第一附属医院临床药理研究室,南京210029 [2]广西壮族自治区人民医院药物临床试验机构办公室,南宁530021

出　　处：《中国临床药理学杂志》2018年第7期866-869,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(81503160)

摘　　要：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。Objective To develop a LC -MS/MS method for the deter- mination of antofloxacin in human plasma and to study the pharmacoki- netic characteristics of antofloxacin after oral administration of antofloxa- cin hydrochloride tablets. Methods The samples were precipitated by acetonitrile and ornidazole was selected as the internal standard. The separation was carried on a Agilent Poroshell 120 SB -C1s（2. 1 mm x 50 mm, 2.7 μm） column with a mobile phase of acetonitrile：5 mmol · L-1 ammonium formate （containing 0. 1% formic acid） = 12：88 at a flow of 0.4 mL · min-1 12 healthy subjects were given orally single dose of antofloxacin hydrochloride 400 mg dose, blood samples were collected at different time points, the concentration of antofloxacin in human plasma was measured, and the main pharmacokinetic parameters were calculated by DAS 2. 1.1 and Excel 2003. Results All the analytes showed good linearity over their concentration ranges on 0.01 - 15.00 μg·m L-1The accuracy, inter- run and intra -run precisions were all below 15%. Analytes were stable during the study. The main pharmacokinetic parameters after antofloxaein 400 mg single drug administration ： Cm,x was （3.57 ± 0.54） μg·m L-1, tmat was （ 2. 25 ± 0. 92 ） h, t1/2 was（ 11.76 ± 1.64） h, AUC0, was （ 60.38 ± 7.47 ） μg·m L-1 h. Conclusion This method can be used to determine the concentration of antofloxacin in human plasma and to study the pharmacokinetics of antofloxacin hydrochloride tablets.

关 键 词：安妥沙星 LC-MS/MS法 药代动力学 

分 类 号：R978.1[医药卫生—药品]