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

Published

Journal Article

A potent and selective sulfonamide beta3 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 SO(2). 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 SO(2) 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 SO(2) has been proposed.

Full Text

Duke Authors

Cited Authors

  • Wang, Z; Hop, CECA; Kim, M-S; Huskey, S-EW; Baillie, TA; Guan, Z

Published Date

  • January 2003

Published In

Volume / Issue

  • 17 / 1

Start / End Page

  • 81 - 86

PubMed ID

  • 12478558

Pubmed Central ID

  • 12478558

Electronic International Standard Serial Number (EISSN)

  • 1097-0231

International Standard Serial Number (ISSN)

  • 0951-4198

Digital Object Identifier (DOI)

  • 10.1002/rcm.877

Language

  • eng