The unanticipated loss of SO2 from sulfonamides in collision-induced dissociation.
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.
Wang
Zhen
Z
Department of Drug Metabolism, Merck Research Laboratories, Rahway, NJ 07065-0900, USA. zhen_wang@merck.com
Hop
Cornelis E C A
CE
Kim
Mi-Sook
MS
Huskey
Su-E W
SE
Baillie
Thomas A
TA
Guan
Ziqiang
Z
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D017357:Cyclotrons; D005583:Fourier Analysis; D007477:Ions / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D013058:Mass Spectrometry; D015394:Molecular Structure; D008970:Molecular Weight; D051381:Rats; D017207:Rats, Sprague-Dawley; D013416:Sulfamerazine / Q000737:chemistry; D013431:Sulfates / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry* / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D007477:Ions; C470788:N-(4-(2-(2-hydroxy-2-pyridin-3-ylethylamino)ethyl)phenyl)-4-(4-(4-trifluoromethylphenyl)thiazol-2-yl)benzsulfonamide; D013431:Sulfates; D013449:Sulfonamides; D013844:Thiazoles; D013416:Sulfamerazine