Abstract
The glutathione conjugate of 2-furamide has been screened for and structurally characterized by tandem mass spectrometry (MS(MS) by using a hybrid instrument of BEqQ design. Mass spectrometry experiments employed fast atom bombardment (FAB) ionization of a crude bile extract from a rat dosed with a 1:1 mixture of unlabeled and [ 13C12-furamide. Initial screening for glutathione conjugates employed constant neutral loss scanning to detect the loss of 129 u, corresponding to the loss of the γ-glutamyl moiety of the conjugates. By direct comparison with control bile, [M + H] + ions of m/z 417 and 418 were readily identified as candidate ions corresponding to the glutathione conjugates of unlabeled and 13C-labeled 2-furamide. Complementary screening information was generated by using a methylated bile extract, with constant neutral loss scanning to detect the loss of the methylated γ-glutamyl moiety (143 u). An alternative screening procedure employing parent ion scanning to detect the sodium adducts of methylated glutathione conjugates was also developed. Structural information was generated by frrst-generation product ion scanning of the protonated and sodium cationized forms of the candidate species, both native and derivatized. This provided a body of internally consistent evidence that the conjugate retains the pseudoaromatic furan ring system without ring hydroxylation. The utility of sequential mass spectrometry (MS(MS(MS) capability of the hybrid instrument in the analysis of complex biological mixtures was also demonstrated. Using the bile extract, first-generation product ions that formed in either the first or second field-free region of the double-focusing portion of the instrument were subsequently collisionally activated in the rf-only quadrupole followed by mass analysis of the second-generation product ions. Structural information so provided for the glutathione conjugate of 2-furamide further substantiated its retention of the pseudoaromatic furan ring system and facilitated plausible assignment of structures to ionic species generated through multiple decomposition events.
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Ballard, K.D., Raftery, M.J., Jaeschke, H. et al. Multiple scan modes in the hybrid tandem mass spectrometric screening and characterization of the glutathione conjugate of 2-furamide. J Am Soc Spectrom 2, 55–68 (1991). https://doi.org/10.1016/1044-0305(91)80061-B
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DOI: https://doi.org/10.1016/1044-0305(91)80061-B