Illuminating the exposome with high-resolution accurate-mass mass spectrometry and nontargeted analysis

Exposomics seeks a comprehensive understanding of the links between human health and environmental chemical ex-posures. Analytical chemistry tools capable of identifying low-level organic contaminants in complex environmental samples are needed to meet the demands of exposomics studies. High -resolution accurate-mass mass spectrometry (HR/AM MS) and nontargeted analysis currently provide the only framework capable of achieving the sensitivity, specificity, and throughput required by large-scale exposomics studies. However, prac-tical tools for the automated and reproducible structure anno-tation of small molecules by HR/AM MS remain underdeveloped. Herein, we review the principles of and recent advances in HR/AM MS-enabled nontargeted analysis with an emphasis on approaches to assigning chemical information to HR/AM MS data.