Applications of tandem mass spectrometry to the characterization of derivatized glutathione conjugates. Studies with S-(N-methylcarbamoyl)glutathione, a metabolite of the antineoplastic agent N-methylformamide.
Daughter ion spectra are reported for [M + H]+ ions generated by fast atom bombardment mass spectrometry of S-(N-methylcarbamoyl)glutathione (1) and a series of alkoxycarbonyl methyl ester derivatives thereof. Structurally informative, even-electron fragment ions, which serve to define the nature of both the xenobiotic and peptide components of the conjugate, are observed in the collisionally activated dissociation (CAD) spectra of 1 and its ethoxy- and benzyloxycarbonyl methyl esters. Studies with the t-butyloxycarbonyl (tBOC) methyl ester derivative, on the other hand, indicated that the tBOC group exerts a powerful directing influence on the CAD process, and that the major daughter ions in this case are associated with cleavage of the tBOC functionality itself and are of little diagnostic value. Of the derivatives examined, the benzyloxycarbonyl congener, which may be generated readily from 1 in aqueous media, is judged to be the most useful from the standpoints of ease of formation, desirable high-performance liquid chromatographic properties, and informative mass spectral fragmentation characteristics under CAD conditions.
Pearson
P G
PG
Department of Medicinal Chemistry, School of Pharmacy, University of Washington, Seattle 98195.
Threadgill
M D
MD
Howald
W N
WN
Baillie
T A
TA
D000818:Animals; D000970:Antineoplastic Agents / Q000032:analysis / Q000378:metabolism*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005559:Formamides / Q000032:analysis / Q000378:metabolism*; D005978:Glutathione / Q000031:analogs & derivatives* / Q000032:analysis*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains
D000970:Antineoplastic Agents; D005559:Formamides; C053323:S-(N-methylcarbamoyl)glutathione; D005978:Glutathione; C002950:methylformamide