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

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.