Advances and perspectives in chemical isotope labeling-based mass spectrometry methods for metabolome and exposome analysis

Metabolomics and exposomics are important in the studies of human health and diseases. Chemical isotope labeling (CIL) combined with mass spectrometry (MS) can not only improve sensitivity but also bring significant benefits for selectivity, accuracy, omics coverage, and analysis throughput. Therefore, MS-based CIL techniques have been increasingly used in metabolome and exposome analysis. In this review, we summarize the advantages of MS-based CIL techniques in sensitivity, accuracy, selectivity, stability, analysis throughput, and applicability, and also discuss the potential shortcomings. Moreover, based on five subgroups of representative metabolites and xenobiotics containing amino, carboxyl, carbonyl, hydroxyl and sulfhydryl groups, we review the advances of MS-based CIL techniques in targeted and not-targeted analysis. Notably, some novel CIL techniques emerged in the structural design of CIL reagents has also discussed. Finally, we give our perspective on the future of MS-based CIL techniques in this field, especially on the structural design of ideal CIL reagents.