Overview

• Published on August 22 in Nature Protocols, the method provides step-by-step guidance for untargeted and semi-targeted analyses of metabolites from cells, tissues and biofluids.
• An inline electrolytic ion suppressor neutralizes hydroxide ions and removes counterions after separation, producing a neutral aqueous eluent optimized for negative-ion MS and enabling direct coupling.
• The workflow requires minimal sample preparation and delivers robust, sensitive and selective measurements across hundreds of metabolites spanning core metabolic pathways.
• The approach resolves a decades-old barrier that made direct coupling of ion-exchange chromatography to mass spectrometry difficult since the 1970s.
• Demonstrated and planned applications include circulating microbiome-derived butyrate studies, diabetic β-cell metabolism, gut microbiome research, antimicrobial resistance effects on bacterial metabolism and early cancer biomarker discovery.