摘要
目的：建立LC-MS/MS法测定人血浆中硫辛酸浓度,并对口服0.2 g硫辛酸分散片后的药代动力学进行研究。方法：血浆样品以萘普生为内标,经乙腈沉淀蛋白后进行LC-MS/MS分析。采用高效液相分离系统,色谱柱为Venuseil XPB C18柱（150 mm×2.1 mm,5μm）,流动相为乙腈-10 mmol·L^-1醋酸铵-甲酸（80∶20∶0.2）;采用质谱检测系统,ESI离子源,负离子模式,多反应监测（MRM）方式监测m/z 205→m/z 171（硫辛酸）和m/z 229→m/z 170（萘普生,内标）。结果：建立的LCMS/MS法在2.500-5 000 ng·m L^-1质量浓度范围内,硫辛酸色谱响应与质量浓度相关性良好,定量下限为2.500 ng·m L^-1;批内及批间精密度RSD均小于7%,准确度在96.5%-101.6%。12名受试者单次服用0.2 g硫辛酸分散片后AUC0-t为（1 816±885.6）ng·m L^-1·h,AUC0-∞为（1 837±879.6）ng·m L^-1·h,Cmax为（3 432±2 410）ng·m L^-1,tmax为（0.45±0.44）h,t1/2为（0.45±0.18）h,MRT为（0.73±0.31）h,CL为（133.2±66.63）L·h-1,Vd为（85.60±50.98）L。结论：本测定方法灵敏准确,适用于人血浆中硫辛酸浓度的测定及其药代动力学研究。
Objective： To develop a sensitive and specific LC-MS / MS method for determination of lipoic acid in human plasma and to study its pharmacokinetic feature in healthy volunteers after a single dose of 0. 2 g lipoic acid dispersible tablets. Methods： After adding naproxen as the internal standard,plasma was deproteinized with acetonitrile. The analyte was isocratically eluted on a Venuseil XPB C18column（ 150 mm × 2. 1 mm,5 μm） with acetonitrile-10 mmol·L^-1ammonium acetate-formic acid（ 80 ∶ 20 ∶ 0. 2） by LC-MS / MS with negative ionization. Ions monitored in the multiple reaction monitoring（ MRM） mode were m / z 205 →m / z 171 for lipoic acid and m / z 229 →m / z 170 for naproxen（ IS）. Results： The linear range of the standard curve of lipoic acid was from2. 500 ng·m L^-1to 5 000 ng·m L^-1. The lower limit of quantitation（ LLOQ） of lipoic acid was 2. 500 ng·m L^-1and RSD of intra-and inter-batch precisions was less than 7%,and the accuracy was between 96. 5%-101. 6%.The analysis showed AUC0-twas（ 1 816 ± 885. 6） ng·m L^-1·h,AUC0-∞（ 1 837 ±879. 6） ng·m L^-1·h,Cmax（ 3 432 ±2 410） ng·m L^-1,tmax（ 0. 45 ± 0. 44） h,t1 /2（ 0. 45 ± 0. 18） h,MRT（ 0. 73 ± 0. 31） h,CL（ 133. 2 ± 66. 63） L·h-1,Vd（ 85. 60 ±50. 98） L in 12 volunteers after a single dose of 0. 2 g lipoic acid dispersible tablets. Conclusion： The established LC-MS / MS method is highly sensitive and accurate,which is suitable for the pharmacokinetic study of lipoic acid in human plasma.
出处
《药物分析杂志》
CAS
CSCD
北大核心
2015年第1期70-74,共5页
Chinese Journal of Pharmaceutical Analysis
基金
山东大学第二医院青年基金项目资助(Y2013010075)
关键词
维生素B类药物
硫辛酸
萘普生
生物样品测定
药代动力学
液相色谱-质谱
vitamin B class drug
lipoic acid
naproxen
biological sample determination
pharmacokinetics
liquid chromatography-mass spectrometry
