Bioactive compounds in functional food using mass spectrometry: A systematic review

This systematic review provides a comprehensive, data-centric overview of bioactive compound discovery in functional foods using mass spectrometry (MS) between 2020 and 2025. Evaluating 250 foodomics studies, we identified over 2000 unique molecules across 14 food macro-categories and 11 molecular classes. Phenolic compounds, specifically ferulic acid, gallic acid, and rutin, emerged as the most pervasive markers, particularly in fruits and botanicals. Methodological analysis reveals that while UHPLC-ESI-QTOF-MS/MS dominates untargeted discovery, significant analytical vulnerabilities remain, including solvent-induced extraction biases, thermal degradation, and severe matrix effects leading to ion suppression. We highlight a critical standardization gap, where the over-reliance on automated spectral library matching without authentic standard validation frequently leads to false-positive annotations. This review synthesizes the current state of MS-bioactive compounds in foodomics, provides a critical evaluation of chemometric workflows, and advocates for integrated analytical strategies, combining untargeted HRMS discovery with targeted QqQ quantification, to ensure the structural and functional integrity of bioactive compounds in functional food research.