中文摘要：

已有报道一些药物进入体内后在各种代谢酶的作用下转化为反应性代谢物，然后与生物大分子（如蛋白、DNA）共价结合，导致毒性。在药物发现和开发阶段进行反应性代谢物筛查，对上市药物进行反应性代谢物监测已经成为一个重要的研究领域。通常，反应性代谢物具有亲电性，能被小分子亲核试剂（如谷胱甘肽及其衍生物、氰离子、胺类等）体外捕获，采用液相色谱一串联质谱法检测并鉴定这些结合物的结构是研究反应性代谢物的基本方法。本文综述了液相色谱与不同质谱仪联用（三重四极杆、离子阱、四极杆一线性离子阱、高分辨质谱仪）检测反应性代谢产物的方法以及应用进展。

英文摘要：

A number of therapeutical drugs were reported to undergo metabolic activation by drug-metabolizing enzymes. The bioactivation forms reactive metabolite（s）, which readily covalently bind to macromolecules, such as proteins and DNA, and then lead to toxicities. In recent years, screening drug candidates for their tendency to generate reactive metabolites during drug discovery and development process and as well monitoring the bioactivation for post-marketing drugs have become increasingly important. Most reactive metabolites are electrophilic in nature and can react with nucleophiles. In vitro microsomal incubations, small nucleophilic molecules, such as glutathione, cyanide and amines are generally used to trap reactive metabolites. Structural elucidation of these stable adducts are conducted by liquid chromatography-tandem mass spectrometry. In this review, different mass spectrometers including triple quadrupole, ion trap, quadrupole-linear ion trap, and high-resolution mass spectrometer, employed for assessing reactive metabolites are described. The recent advances of different techniques and approaches are also discussed.