Mass spectrometry does produce different ion forms, but claiming the metabolome is mostly known is misleading. Analysis LC-MS data of 30,000 chemical standards found fewer in-source fragments than expected, suggesting they’re not as prevalent in biological samples as some argue. Even within a well-studied US National Institute of Standards and Technology (NIST) human fecal reference standard dataset, a staggering 82% of molecules lacked annotations for any ion form when carefully grouped by retention time, MS/MS data, and peak shape. This compelling finding underscores that the dark metabolome remains a significant frontier for discovery, holding countless unannotated features that could potentially represent novel molecules or provide crucial biochemical insights.
Y El Abiead et al. Nat. Metab. (2025) doi: 10.1038/s42255-025-01239-4
