Yamaoka, Toshikazu published the artcileCharacterization of a highly sensitive and selective novel trapping reagent, stable isotope labeled glutathione ethyl ester, for the detection of reactive metabolites, HPLC of Formula: 40180-04-9, the main research area is reactive metabolite stable isotope glutathione ethyl ester trapping reagent; Bioactivation; Glutathione trapping assay; Idiosyncratic toxicity; Reactive intermediate; Stable isotope.
Glutathione (GSH) trapping assays are widely used to predict the post-marketing risk for idiosyncratic drug reactions (IDRs) in the pharmaceutical industry. Although several GSH derivatives have been introduced as trapping reagents for reactive intermediates, more sensitive and selective reagents are desired to prevent the generation of erroneous results. In this study, stable isotope labeled GSH Et ester (GSHEE-d5) was designed and its detection capability was evaluated. GSHEE-d5 was synthesized and its detection potential was compared with stable isotope labeled GSH ([13C2,15N]GSH) as a reference trapping reagent. The trapping reagents were added to human liver microsomes as a 1:1 mixture with GSHEE or GSH, resp., and incubated with seven IDR pos. drugs and three IDR neg. drugs. The adducts formed between the reagents and reactive metabolites were analyzed by unit resolution mass spectrometer (MS) using isotope pattern-dependent scan with neutral loss filtering. A single-step reaction of GSH and ethanol-d6 produced GSHEE-d5 with a yield of 85%. The GSHEE-d5 assay detected adducts with all seven IDR pos. drugs, and no adducts were detected with the three IDR neg. drugs. In contrast, the [13C2,15N]GSH assay failed to detect adducts with three of the IDR pos. drugs. In the case of diclofenac, the GSHEE-d5 assay showed a 4-times greater signal intensity than the [13C2,15N]GSH assay. GSHEE-d5 enabled the detection of reactive metabolites with greater sensitivity and selectivity than [13C2,15N]GSH. These results demonstrate that GSHEE-d5 would be a useful trapping reagent for evaluating the risk of IDRs with unit resolution MS.
Journal of Pharmacological and Toxicological Methods published new progress about Homo sapiens. 40180-04-9 belongs to class benzothiophene, name is 2-(2,3-Dichloro-4-(thiophene-2-carbonyl)phenoxy)acetic acid, and the molecular formula is C13H8Cl2O4S, HPLC of Formula: 40180-04-9.
Referemce:
Benzothiophene – Wikipedia,
Benzothiophene | C8H6S – PubChem