confirmed that the molecular weight increased to m/z 534, indicating that there were seven exchangeable protons in this GSH adduct, of which six were contributed by GSH. This result suggested that the metabolite was a GSH adduct of a free thiol formed through the opening of the thiophene ring. The free thiol provided the extra exchangeable proton and the opened ring could be envisioned to close during fragmentation to yield product ions that correspond to GSH and 2-(4-methoxybenzoyl)thiophene.
To further confirm the structure of this GSH adduct, dansylaziridine was used to derivatize the free-thiol group. Thiol groups react specifically with dansylaziridine to form dansyl-sulfonamide derivatives . Figure 10.7 shows the product-ion MS/MS spectrum and the proposed fragmentation scheme of the dansylaziridine-derived ring-opened GSH adduct. Loss of glycine and GSH from the molecular ion ([M + H]+ at m/z 802) generated the product ions at m/z 727 and m/z 495. The product ion at m/z 135 corresponds to the 4-methoxybenzaldehyde portion of the molecule. The fragmentation pattern was very similar for the iodoacetic acid-derived ring-opened GSH adduct shown in Figure 10.8. Loss of GSH from the molecular ion ([M + H]+ at m/z 584) generated the product ion at m/z 277 and the product-ion at m/z 135, which corresponded to the 4-methoxybenzaldehyde portion of the molecule.
An electrophilic a,p-unsaturated aldehyde intermediate was also formed in rat and human liver microsomes in the presence of reduced form of nicotinamide adenosine dinucleotide phosphate (NADPH), and its structure
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