Advancing Untargeted Metabolomics Through FT-ICR-MS: Challenges and Applications

Metabolomics is the study of the complete set of small molecules involved in the biochemical processes within a biological system. It links directly to metabolism, capturing the biochemical pathways and processes in a state-specific manner and aiming to understand the dynamic interactions within these metabolites, including how they reflect the physiological and environmental conditions as well as cellular and physiological responses. Presently, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) is the highest performance mass spectrometry technology for untargeted metabolomic analysis, allowing the simultaneous detection of thousands of compounds in a single analysis. This analytical performance is due to its extreme mass resolution and exceptional mass accuracy, unmatched by any other type of mass spectrometer. This technology enables precise identification and differentiation of metabolites within complex biological samples, providing highly accurate molecular formulas, based on exact mass and fine isotopic distribution. This review focuses on new developments in FT-ICR-MS technology for metabolomic analysis, new methodologies and recent applications. It also addresses the current challenges and perspectives for the use of FT-ICR-MS in metabolomics.