Evaluating Exposome Analysis Using LC–MS and GC–MS

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A team from Örebro University and the University of Turku and Åbo Akademi University has recently looked at how using alternate approaches alongside liquid- and gas chromatography–mass spectrometry (LC–MS and GC–MS) methods can streamline and improve exposome analysis. Their findings were published in the Journal of Chromatography A (1).

Research equipment, gas chromatograph. Scientific machine for studying the composition of a substance. | Image Credit: © nordroden - stock.adobe.com

Research equipment, gas chromatograph. Scientific machine for studying the composition of a substance. | Image Credit: © nordroden - stock.adobe.com

An exposome is defined as the measure of all an individual’s exposures in a lifetime, and how those exposures relate to health (2). With environmental factors playing a critical role in human health, exposome research aims to explore the effects of these factors by capturing chemical, biological, and physical stressors and their association with human (patho)physiological responses. By determining external exposures, biological responses to exposures, or host susceptibility at a systems level, one can establish links between the exposome and health outcomes. However, characterizing one’s exposome is challenging because exposome profiles are highly dynamic, individual-based, and associated with both nonchemical parameters (lifestyle, demographic factors) and the chemical profiles of inorganic and organic substances.

Due to the complexity of the chemical space in exposome research, analytical approaches typically combine various types of methods, including target, non-target, and suspect screening methods. LC–MS and GC–MS are typically used for this approach, with the goal being to comprehensively cover endogenous and exogenous substances, with some tradeoffs in the accuracy of the compounds detected. MS-based methods are vital to exposome research because they possess the ability to explore a broad spectrum of chemical exposures. However, the use of MS comes with its own set of challenges, such as the complexity of MS data, requiring the expertise of biologists, chemists, clinicians, and data analysts to integrate and interpret MS data with other datasets.

For this review, the scientists focused on analytical approaches applied to a comprehensive chemical profiling of organic substances, including both endogenous metabolites as well as xenobiotics, with a focus on environmental pollutants. According to the scientists, the “omics” era advances rapidly, which stems from constant developments of AI-based algorithms and increases in accessible data; that said, further efforts are necessary to ensure that exposomics outputs are comparable and reproducible, thus enhancing research findings (1).

Comprehensive exposomics workflows require nonselective extraction methods and robust GC–MS and LC–MS techniques. These techniques can be hyphenated with different approaches, such as ion mobility spectrometry (IMS). Using high-resolution MS (HRMS) analyzers alongside these techniques offers advantages, such as improved separation/annotation.

These experimental approaches must all be followed by proper quality control and consistent reporting standards to ensure their robustness and reproducibility. Further, while environmental monitoring is a large part of exposomics, it is not the only field where exposomes matter. Exposomics encompasses a broader chemical space, which hopes to explore the relationship between human metabolism and xenobiotics (foreign chemicals that may accumulate in the body and affect the normal metabolism of a living organism) (3). Looking into this dynamic can provide a more comprehensive understanding of how exposure affects human health. Overall, when properly approached and integrated with other data, exposomics can help uncover complex human-environment interactions and advance personalized healthcare.

References

(1) Castro-Alves, V.; Nguyen, A. H.; Barbosa, J. M. G.; Orešič, M.; Hyötyläinen, T. Liquid and Gas-Chromatography-Mass Spectrometry Methods for Exposome Analysis. J. Chromatogr. A 2025, 1744, 465728. DOI: 10.1016/j.chroma.2025.465728

(2) Exposome and Exposomics. Centers for Disease Control and Prevention 2022. https://archive.cdc.gov/www_cdc_gov/niosh/topics/exposome/default.html (accessed 2025-2-12)

(3) Xenobiotic. ScienceDirect 2022. https://www.sciencedirect.com/topics/immunology-and-microbiology/xenobiotic (accessed 2025-2-12)

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