High-resolution mass spectrometry for metabolomics

Abstract

Objective

To elucidate the potential of high-resolution mass spectrometry (HRMS) in metabolomics, particularly within the field of toxicology.

Metabolomics refers to the simultaneous detection and (semi)-quantification of a large-scale of small molecules, commonly known as endogenous metabolites. Compared to other omics approaches, metabolomics correlates well with phenotype, providing an amplified and dynamic measure of changes resulting from processes involving the genome, transcriptome, proteome, and the environment. Through its ability to highlight changes in the overall metabolic profile rather than focusing on a single metabolite, metabolomics presents itself as a promising tool for elucidating physiopathological mechanisms or even identifying new biomarkers, including in the field of toxicology.

Methods

Metabolomic can follow either a targeted (hypothesis-driven) or an untargeted (hypothesis-generating) approach. Common technological tools for metabolomic data production are based on nuclear magnetic resonance spectroscopy and mass spectrometry, each with complementary properties regarding sensitivity and metabolome coverage. HRMS-based metabolomics is particularly powerful, as it offers a high sensitivity and accuracy, broad chemical coverage, and, above all, enhanced structural information, enabling better identification of unknown features. For these reasons, HRMS is especially well suited for untargeted metabolomic approaches.

Results

HRMS-based metabolomics shows significant potential to address unmet clinical needs in biological and forensic toxicology by confirming exposure, effects, and/or toxicity related to xenobiotics, and enhancing post-mortem interpretation in forensic cases. As a highly dynamic and rapidly evolving field, biological and forensic toxicology are constantly confronted with new challenges, such as the need to confirm acute drug consumption, extend detection windows, discriminate addiction from occasional consumers, improve post-mortem investigations (cause of death, post-mortem interval), provide unambiguous evidence of sports doping.

Discussion–conclusion

Although HRMS applications have been demonstrated in several research contexts, challenges remain before it can be fully implemented in routine forensic and clinical practice. Key obstacles include the technical complexity of data interpretation and bioinformatic workflows, along with a lack of standardized protocols.