高效液相色谱-高分辨质谱法研究药物代谢产物的数据处理策略

摘要

高效液相色谱-高分辨质谱(HPLC-HRMS)联用技术具有高灵敏度、快速和高质量准确度的特点,是药物代谢产物分析的有力手段.通过使用HPLC-HRMS产生高分辨质谱数据(高分辨质量数、多级质谱数据、同位素分布),结合多重采集后数据处理技术,可用于药物代谢产物的快速发现和结构鉴定.本工作综述了近年来基于HPLC-HRMS技术应用最为广泛的几种数据挖掘策略及应用,如,提取离子色谱、质量亏损过滤、同位素过滤、本底扣除、产物离子过滤、质谱树状图过滤、SWATH和MSE以及这些技术的联用等.通过合理地使用其中一种或几种策略对HPLC-HRMS产生的数据进行处理,可以有效地进行药物代谢产物的发现和鉴定.%High performance chromatography coupled with high-resolution mass spectrometer (HPLC-HRMS) has been widely used to discover and identify drug metabolites due to its high sensitivity, rapidity and high mass accuracy.Drug metabolites can be rapidly detected and identified based on mass data (high resolution mass and multiple stage mass) and mass data processing strategy.This paper reviews the strategies and applications for the discovery and identification of drug metabolites using HPLC-HRMS after consulting related papers in recent years.These strategies, including extracted-ion chromatography (EIC), mass defect filter (MDF), isotope pattern filter (IPF), background subtraction (BS), product ion filter (PIF), mass spectral trees similarity filter (MTSF), SWATH and MSE, were developed for the detection and identification of drug metabolites in complex biologic systems.Drug metabolites can be effectively detected and identified through the joint application of one or more strategies.