Global Profiling of Urinary Mercapturic Acids Using Integrated Library-Guided Analysis

Wedescribe an exposomics platform for profiling of urinarymercapturic acid metabolites derived from reactive chemicals of environmentaland endogenous origins. Urinary mercapturic acids (MAs) areoften used as biomarkers formonitoring human exposures to occupational and environmental xenobiotics.In this study, we developed an integrated library-guided analysisworkflow using ultraperformance liquid chromatography-quadrupoletime-of-flight mass spectrometry. This method includes expanded assignmentcriteria and a curated library of 220 MAs and addresses the shortcomingsof previous untargeted approaches. We employed this workflow to profileMAs in the urine of 70 participants 40 nonsmokers and 30 smokers.We found approximately 500 MA candidates in each urine sample, and116 MAs from 63 precursors were putatively annotated. These include25 previously unreported MAs derived mostly from alkenals and hydroxyalkenals.Levels of 68 MAs were comparable in nonsmokers and smokers, 2 MAswere higher in nonsmokers, and 46 MAs were elevated in smokers. Theseincluded MAs of polycyclic aromatic hydrocarbons and hydroxyalkenalsand those derived from toxicants present in cigarette smoke (e.g.,acrolein, 1,3-butadiene, isoprene, acrylamide, benzene, and toluene).Our workflow allowed profiling of known and unreported MAs from endogenousand environmental sources, and the levels of several MAs were increasedin smokers. Our method can also be expanded and applied to other exposure-wideassociation studies.

Automated summary

We developed an exposomics platform to analyze urinary mercapturic acid metabolites from reactive chemicals. Our workflow enabled profiling of known and unreported MAs from endogenous and environmental sources, and revealed increased levels of several MAs in smokers. This method has wide applications in exposure-wide association studies.