Recent Advances in Small Molecule Metabolites Analysis by Ion Mobility-Mass Spectrometry

Recently, different types of ion mobility techniques have sprung up. Combined with mass spectrometry, the utility of ion mobility spectrometry has been enhanced in metabolomics, natural products, characterization of supramolecular materials, and other research fields. Since small molecule metabolites provide deep insight into the dynamic phenotypes of biological systems and show potential value in disease diagnosis and functional interpretation, in-depth analysis of small molecule metabolites plays a key role in medicine and pharmacy. The potential benefits of ion mobility spectrometry used in chiral recognition of amino acids, structural analysis of glycans, and structural characterization of lipids and steroids have become the specific focus of work. However, small molecule metabolites possess a wide variety of chemical properties, ubiquitous isomerism, and various biological functions, so it is difficult to analyze small molecule metabolites comprehensively. On the other hand, small molecule metabolites with low concentrations usually exist in various complex biological matrices, such as plasma, feces, urine, saliva, sweat, infected tissues or exudates, breath, and breast milk, which pose additional challenges to researchers. Over the last few decades, ion mobility-mass spectrometry (IM-MS) has undergone inordinate growth in instrument development and performance, which has opened a new door to rapidly analyze small molecular metabolites in complex biological matrices. Small molecular metabolites and their isomers can be distinguished and characterized in milliseconds by IM-MS that offer high selectivity and three-dimensional information about them, including mass-charge ratio, collision cross section (CCS), and structural information. The collision cross section can be used as an additional identification basis in targeted and untargeted analyses. In this paper, the main commercial IM-MS instruments were briefly covered. An overview of the latest applications in small molecular metabolites was offered. Additionally, the advantages and shortcomings of IM-MS in the analysis of small molecular metabolites were discussed. And the future application of particular and unknown metabolites by IM-MS in the studies on the biological mechanism and precision medicine was prospected.