Characterization of glutathione conjugates by fast atom bombardment/tandem mass spectrometry.

The collisionally activated decomposition of [M + H]+ ions, generated by fast atom bombardment (FAB) of glutathione conjugates, has been studied by tandem mass spectrometry (MS/MS) using hybrid sector/quadrupole instruments. Abundant fragments of diagnostic utility were present in the daughter ion spectra. Common fragmentation modes were observed but their relative importance was strongly dependent on the nature of the conjugated species. As an example of a general approach to the characterization of glutathione conjugates in biological samples, the acetaminophen-glutathione conjugate was identified in rat bile, following coadministration of (2H0)- and (2H3)acetaminophen, using the experimental sequence: (i) conventional FAB mass spectrometric analysis, (ii) MS/MS using constant neutral loss (129 u) scanning to identify parent ions corresponding to glutathione conjugates, (iii) MS/MS to yield daughter ion spectra of parents so identified and corresponding to (2H0)- and (2H3)-labeled conjugates.