کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
218086 463181 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Electrochemistry-coupled to mass spectrometry in simulation of metabolic oxidation of methimazole: Identification and characterization of metabolites
ترجمه فارسی عنوان
الکتروشیمیایی با طیف سنجی جرمی در شبیه سازی اکسیداسیون متابولیک ممازول: شناسایی و مشخص کردن متابولیت ها
کلمات کلیدی
موضوعات مرتبط
مهندسی و علوم پایه مهندسی شیمی مهندسی شیمی (عمومی)
چکیده انگلیسی


• This manuscript involves the mimicry of metabolic activation of Methimazole using an electrochemical technique.
• Using this electrochemical technique, we have been able to detect genotoxic metabolites that had been hitherto elusive.
• We can use this technique to rationalize observed toxicities associated with this drug.

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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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Electroanalytical Chemistry - Volume 761, 15 January 2016, Pages 131–140
نویسندگان
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