化学
质谱法
电化学
电喷雾电离
代谢物
自旋俘获
亚硫酸
激进的
光化学
组合化学
色谱法
有机化学
生物化学
电极
物理化学
作者
Kudzanai Chipiso,Reuben H. Simoyi
标识
DOI:10.1016/j.jelechem.2015.10.041
摘要
Methimazole (MMI), an antithyroid drug, is associated with idiosyncratic toxicity. Reactive metabolites resulting from bioactivation of the drug have been implicated in these adverse drug reactions. Mimicry of enzymatic oxidation of MMI was carried out by electrochemically oxidizing MMI using a coulometric flow-through cell equipped with a porous graphite working electrode. The cell was coupled on-line to electrospray ionization mass spectrometry (EC/ESI-MS). ESI spectra were acquired in both negative and positive modes. In acidic medium, ESI spectral analysis showed that the dimer was the main product, while in neutral and basic media, methimazole sulfenic acid, methimazole sulfinic acid and methimazole sulfonic acid were observed as the major electrochemical oxidation products. Oxidation of MMI and subsequent trapping with nucleophiles resulted in formation of adducts with N-acetylcysteine. Some of the electrochemically generated species observed in these experiments were similar to metabolites that have been observed from in vitro and in vivo studies. Trapping studies also showed that bioactivation of MMI proceeds predominantly through the S-oxide and not through formation of thiyl radicals. These results show that electrochemistry coupled to mass spectrometry can be used in mimicry of oxidative metabolism and subsequent high throughput screening of metabolites.
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