Get access

The unanticipated loss of SO2 from sulfonamides in collision-induced dissociation



A potent and selective sulfonamide β3 agonist with an excellent pharmacokinetic profile has recently been synthesized. During the analysis by liquid chromatography/tandem mass spectrometry (LC/MS/MS) of metabolites of the sulfonamide N-{4-[2-(2-hydroxy-2-pyridin-3-ylethylamino)ethyl]phenyl}-4-[4-(4-trifluoromethylphenyl)thiazol-2-yl]benzulfonamide (compound A), we observed loss of 64 Da for a few of the metabolites in the negative ion mode. Accurate mass measurements performed with Fourier transform ion cyclotron resonance (FTICR) mass spectrometry and quadrupole time-of-flight (Q-TOF) mass spectrometry suggested that the loss of 64 Da corresponded to the loss of SO2. The same phenomenon was observed for a group of structurally related and commercially available compounds that also contain a sulfonamide moiety. MS/MS analysis of the fragment ions that had lost SO2 in the ion source suggested that these ions were covalently bound rather than ion-molecule complexes. The neutral loss involving the cleavage of two bonds was unanticipated and suggested a complex rearrangement process. A mechanism for the loss of SO2 has been proposed. Copyright © 2002 John Wiley & Sons, Ltd.