Enhancing tandem mass spectrometry-based metabolite annotation with online chemical labeling
- Giovanni Andrea Vitale
- Shu-Ning Xia
- Kai Dührkop
- Mohammad Reza Zare Shahneh
- Heike Brötz-Oesterhelt
- Yvonne Mast
- Corinna Brungs
- Sebastian Böcker
- Robin Schmid
- Mingxun Wang
- Chambers C. Hughes
- Daniel Petras
2025-07-26
Metabolite identification in non-targeted mass spectrometry-based metabolomics remains a major challenge due to limited spectral library coverage and difficulties in predicting metabolite fragmentation patterns. Here, we introduce Multiplexed Chemical Metabolomics (MCheM), which employs orthogonal post-column derivatization reactions integrated into a unified mass spectrometry data framework. MCheM generates orthogonal structural information that substantially improves metabolite annotation through in silico spectrum matching and open-modification searches, offering a powerful new toolbox for the structure elucidation of unknown metabolites at scale.