Isomers are compounds with the same molecular formula. Many different types of isomers are ubiquitous and play important roles in living organisms. Despite their early discovery, the actual analysis of isomers has been tricky and has confounded researchers. Using mass spectrometry (MS) to distinguish or identify isomers is an emergent topic and challenge for analytical chemists. We review some techniques for analyzing isomers with emphasis on MS, e.g., the roles of ion reaction, hydrogen–deuterium exchange, ion mobility mass spectrometry, ion spectroscopy, and energy change in producing isomer-specific fragments. In particular, soft ionization for gas chromatography–mass spectrometry (GC–MS) is a focus in this review. Awareness of the advantages and technical problems of these techniques would inspire innovation in future approaches.
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