Fast-atom bombardment and thermospray mass spectrometry for the characterization of two glucuronide metabolites of methapyrilene

Two conjugated metabolites of methapyrilene hydrochloride isolated from mouse-hepatocytes were examined by mass spectrometry using fast-atom bombardment (FAB) and thermospray ionization. The major metabolite, methapyrilene glucuronide, was identified based on a prominent peak due to the protonated molecule as well as the loss of the dimethylamine and sugar moieties. Identification of the second metabolite was complicated by large signals associated with the biological sample matrix. The complementary nature of the fragmentation observed in the mass spectra using FAB and thermospray ionization allowed this metabolite to be identified as the desmethylmethapyrilene glucuronide. The fragmentation observed using FAB ionization was not greatly affected by the presence of the glucuronide moiety. While loss of the sugar moiety indicated a glucuronide, additional fragmentation confirmed the presence of the underlying ethylenediamine substructure which is characteristic of this class of antihistamines.