Strategies for studying in vivo biochemical formation pathways and multilevel distributions of sulfanilamide metabolites in food (2012-2022).

Sulfonamide metabolites are a major source of food pollution worldwide. However, the formation of internal sulfanilamide metabolites has only been investigated for selected compounds. In this paper, the fragmentation mechanism and characteristic ions of sulfonamide metabolites are reviewed using density functional theory and Q-Orbitrap high-resolution mass spectrometry. The result of the protonation site, rearrangement and bond breaking induced fragmentations at CHNOSm/z 156.01138, CHNOm/z 108.04439, and CHNm/z 92.04948. Mass shifts are calculated for derivative metabolites, including hydrogenation, acetylation, oxidation, glucosylation, glucosidation, sulfation, deamination, formylation, desulfonation and O-aminomethylation. Given their homologous series, it is demonstrated that similar metabolic reactions occur for all sulfonamides. The suspicious sulfonamide metabolites are confirmed by d-labelling experiments and reference standards. This is the first review of the latest advances in the field of sulfonamide metabolite prediction (2012-2022), and scheme design for metabolite multirresidue screening, as well as the challenges in the mass spectrometry evolution.