化学同位素标记-质谱分析技术在环境健康研究中的最新进展

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

代谢组和暴露组的分析表征在环境风险和健康效应研究中具有重要意义。由于人体代谢物和外源性化合物的理化性质多样和样品基质复杂,对其进行综合分析与表征是一项巨大的挑战。质谱(MS)虽然具有强大的定性和定量能力,但存在对一些分析物的灵敏度、特异性等不足的问题。化学同位素标记(CIL)技术与MS结合不仅可以提高检测灵敏度,而且在特异性、准确度、组学覆盖率和分析通量等方面有着显著的优势。近年来,化学同位素标记-质谱(CIL-MS)技术广泛应用于与环境和健康相关的代谢物和暴露标志物的靶向或非靶向分析。本文综述了近3年来CIL-MS在含氨基、羧基、羰基、羟基和巯基的代谢物/外源性化合物研究中的最新进展,关注与其相关的环境风险与健康效应,并总结CIL技术在MS分析中的优势、最新动态以及存在的不足,展望CIL-MS技术的发展趋势。

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.