Establishing a systematic, untargeted framework for the human exposure by high-resolution mass spectrometry

Over a lifetime, humans experience thousands of chemical exposures from multiple sources. A more complete estimate of environmental exposures across the lifespan would be a transformative research initiative. The use of high-resolution, mass spectrometry (HRMS) provides a key platform for assessing the exposome and provides measures of thousands of chemical signals in a single human sample. Untargeted assays for the exposome primarily rely on strategies that were initially developed for metabolomic analysis, resulting in sample preparation, data acquisition and processing, and compound identification methods optimized for high-abundance metabolites. Therefore, current approaches have limited capability to capture many exposure biomarkers present in biological samples at concentrations orders of magnitude lower than endogenous metabolites and a critical need exists to optimize analytical procedures and data processing workflows for detection of exposome chemicals.

This presentation will discuss the limitations of using analytical frameworks primarily optimized for metabolomics analysis for measuring the exposome and highlight recent advances that include incorporating multiple untargeted analytical platforms, sample preparation techniques, data processing and annotation strategies that allow improved capture of exposure biomarkers in human samples. The use of enhanced exposome analytical frameworks based upon untargeted HRMS are poised to provide a robust foundation for exposome research and facilitate development of a knowledge base of environmental chemicals, their products, distributions and associated effects.