LC-MS/MS法同时测定人血浆中福沙匹坦和代谢物阿瑞匹坦  

Simultaneous determination of fosaprepitant and its metabolite aprepitant in human plasma by liquid chromatography-tandem mass spectrometry

作　　者：沈佳乐 昝斌 陈笑艳 钟大放[1,2] 

机构地区：[1]浙江工业大学药学院,浙江杭州310014 [2]中国科学院上海药物研究所,上海201203

出　　处：《药学学报》2018年第1期121-126,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81521005)

摘　　要：建立了LC-MS/MS法同时测定人血浆中福沙匹坦及其代谢物阿瑞匹坦,并应用于中国健康受试者的药动学研究。本法中血浆样品以乙腈沉淀蛋白处理,经Cortex C18+色谱柱(50 mm×2.1 mm,2.7μm)分离,以甲醇-10 mmol·L^(-1)醋酸铵(含0.1 mmol·L^(-1) EDTA)为流动相。采用电喷雾离子源(ESI源),以多反应监测负离子模式检测。以稳定同位素标记内标d_4-福沙匹坦和d_4-阿瑞匹坦分别作为福沙匹坦和阿瑞匹坦的内标,用于定量分析的离子反应分别为m/z 613.1→78.9(福沙匹坦)、m/z 617.0→78.9(d_4-福沙匹坦)、m/z 533.2→275.1(阿瑞匹坦)和m/z 537.2→279.1(d_4-阿瑞匹坦)。由于福沙匹坦为阿瑞匹坦的磷酸化前药,在血浆中快速降解,所以实验中采用碱性缓冲液处理血浆以确保其稳定。测定福沙匹坦标准曲线线性范围为15~6 000 ng·m L^(-1);测定阿瑞匹坦标准曲线线性范围为10~4 000 ng·m L^(-1)。各待测物的日内、日间精密度和准确度均符合生物样品分析相关要求。该方法经验证后,成功应用于12名中国健康受试者静脉滴注150 mg福沙匹坦双葡甲胺后药动学研究。An LC-MS/MS method was developed for the simultaneous determination of fosaprepitant and aprepitant in human plasma,and applied to a pharmacokinetic study of 150 mg fosaprepitant dimeglumine injection to 12 Chinese healthy volunteers.The analytes and internal standards were extracted from plasma by protein precipitation with acetonitrile and separated on a Cortex C18＋（50 mm×2.1 mm,2.7μm）column using a gradient elution procedure.Mass spectrometry was performed in negative MRM mode,and parent-to-produce transitions were as follows：m/z 613.1→78.9 for fosaprepitant,m/z 617.0→78.9 for d4-fosaprepitant,m/z533.2→275.1 for aprepitant and m/z 537.2→279.1 for d4-aprepitant.Plasma sample was basified to stabilize fosaprepitant.The standard curves were demonstrated to be liner in the range of 15.0 to 6 000 ng·mL^-1 for fosaprepitant and 10.0 to 4 000 ng·mL^-1 for aprepitant.The intra-day precisions and inter-day precisions and accuracy were within the acceptable limits for all concentrations.

关 键 词：LC-MS/MS 福沙匹坦 阿瑞匹坦 稳定性 人体药动学 

分 类 号：R917[医药卫生—药物分析学]