化学衍生用于代谢物异构体质谱分析  

Chemical Derivatization for Mass Spectrometric Analysis of Metabolite Isomers

作　　者：王子璇 厉欣 再帕尔·阿不力孜 Zixuan Wang;Xin Li;Zeper Abliz(State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Center for Imaging and Systems Biology,Minzu University of China,Beijing 100081,China)

机构地区：[1]中国医学科学院/北京协和医学院药物研究所天然药物活性物质与功能国家重点实验室,北京100050 [2]中央民族大学生物成像与系统生物学研究中心,北京100081

出　　处：《化学进展》2021年第3期406-416,共11页Progress in Chemistry

基　　金：国家自然科学基金项目(No.21927808);中国医学科学院医学与健康科技创新工程协同创新团队项目(No.2017-I2M-3-010)资助

摘　　要：内源性代谢物是机体生命活动的中间体和终产物,对其进行定性和定量分析在生命科学研究中具有重要意义。质谱能够同时提供化合物的定性和定量信息,已经成为一种通用的内源性代谢物分析技术。由于质谱是通过检测离子质荷比获取化合物组成信息,区分生物体内复杂多样代谢物同分异构体仍然是质谱分析亟待解决的难题之一。化学衍生通过放大同分异构体理化性质差异,能够增强质谱检测的灵敏度和特异性。本文介绍了化学衍生用于代谢物异构体质谱检测的研究进展,对用于脂质、糖类和手性氨基酸等精细结构异构体的化学衍生质谱分析方法及应用进行了综述。特别强调了微液滴化学反应加速在衍生化质谱分析中的发展,其有望成为代谢物实时原位衍生化检测的新方法。此外,将生物组织原位衍生化与质谱成像分析技术相结合,对于研究低丰度、非极性和异构体代谢物的空间分布及其功能具有重要价值。Being the intermediates and final products of life metabolic activities,endogenous metabolites precisely mirror metabolic changes in vivo,providing clues for the study of diseases and other life processes.Mass spectrometry has become a universal technique for qualitative and quantitative analysis of endogenous metabolites,with high sensitivity,high specificity and wide dynamic range.However,it remains a limitation on the detection and differentiation of subtle structural differences of metabolite isomers in heterogeneous biological tissue using mass spectrometry.Therefore,how to improve sensitivity and specificity of mass spectrometry needs to be solved in the study of metabolite isomers’analysis.Chemical derivatization takes advantage of bringing high proton affinity groups,hydrophobicity or chiral selectors to desired analytes,which is expected to broaden the applications of mass spectrometry for analysis of metabolite isomers.In this review,advances in chemical derivatization-based mass spectrometric analysis of metabolic isomers are summarized,including(1)reaction approaches and(2)methods and applications of lipids,carbohydrates and chiral amino acids.Special emphasis is placed on on-line derivatization microdroplet accelerate reaction by mass spectrometry,in which chemical derivatization of analytes occurring simultaneously with spray ionization,providing a promising way for instant and in-situ metabolite derivatization.The emerging study of on-tissue derivatization mass spectrometry imaging is of great value for providing spatial distribution of low abundance,non-polar and isomer metabolites.In the second part,different approach of detailed structural characterization of various compound classes are discussed,with a focus on lipids,carbohydrates and chiral amino acids.

关 键 词：质谱分析 化学衍生 异构体 代谢物分析 反应质谱 

分 类 号：O657.63[理学—分析化学]