Recent Progresses of Chemical Isotope Labeling-based Mass Spectrometry Analysis in Environment and Health Studies

With the development of environmental and health research, the relationship between pollutants exposure and human health effects has become an important research field in recent years. The analysis of metabolome and exposome is of great significance in the studies of environmental risk and health effect. Both metabolomics and exposomics require to deeply analyze the characterization of small molecule metabolites and exogenous compounds in living organisms. Due to the diversity of physicochemical properties of metabolites and xenobiotics and the complexity of sample matrix, their comprehensive analysis and characterization are still a great challenge. Mass spectrometry (MS) has powerful qualitative and quantitative capabilities, but it still lacks sensitivity and specificity for some analytes. Chemical derivatization can introduce predesigned and synthesized chemical groups through chemical labeling reaction, which can significantly change the molecular physicochemical properties of analytes, so as to improve the analytical effect. Although the use of isotope internal standard (ISs) can effectively correct the results of mass spectrometry, ISs have the disadvantages of difficult to synthesize and expensive, and can be purchased in extremely limited types and amounts. To solve the above problems, chemical isotope labeling (CIL) technique has been developed and applied to MSbased metabolome and exposome analysis. Chemical isotope labelingbased mass spectrometry (CILMS) is one of the important solutions for comprehensive analysis of metabolome or exposome. In its workflow, biological samples are derivatized using CIL reagents that target specific chemical functional groups. Metabolites or xenobiotics containing corresponding targeted functional groups react with CIL reagents to produce labeled products. CILMS can not only improve sensitivity, but also has advantages of specificity, accuracy, omics coverage and analytical throughput. In recent years, CILMS technique has been increasingly used for targeted or non-targeted analysis of metabolites and exposure biomarkers about environment and health. The entire metabolome or exposome can be divided into several subgroups based on the chemical functional groups of the analytes, including amino, carboxyl, carbonyl, hydroxyl, sulfhydryl, etc., and then LCMS or other MS analytical method based on CIL technique is performed for each subgroup. The analysis results of each subgroup can be combined to obtain a nearly complete overall profile of metabolome or exposome. This review focused on recent progresses of CIL techniques and MS analytical methods for the analysis of amino, carboxyl, carbonyl, hydroxyl and sulfhydrylcontaining metabolites/xenobiotics, and the related environment risk and health effects in the last 3 years. Meanwhile, the advantages, latest development trends and disadvantages of CIL technique in MS analysis were summarized, and the future development trends of MSbased CIL technique were prospected.