An electrochemical pipette for the study of drug metabolite
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Abstract
Electrochemistry offers an effective means of mimicking enzymatic metabolite pathways, particularly the oxidative pathways catalyzed by the cytochrome P450 superfamily. The electrochemical generation and identification of metabolites are time-sensitive, necessitating adjustable cell designs for accurate mechanistic interpretation.
In chapters one and two, we present a thin-layer electrode (TLE) that addresses the needs of both analytical and synthetic electrochemical generation of drug metabolites. TLE’s ability to conduct experiments on a minute-to-hour timescale allows for detailed observation of reaction mechanisms for metabolites not easily identified by traditional methods.
In chapter three, the utility of the TLE for drug metabolite was benchmarked for electrochemical oxidation of acetaminophen, acebutolol, and 2-acetyl-4-butyramidophenol, known to produce quinone imine metabolites, i.e., NAPQI, upon oxidation. When combined with a microelectrode (μE), the TLE enables probing the concentration profiles for metabolic oxidation of these drugs. The micromole scale and pipette-type structure of the TLE facilitate comprehensive structural elucidation of intermediates and products using chromatographic and spectroscopic techniques.
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Introduction and background -- Experimental -- Results and discussion -- Conclusion and outlook
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M.S. (Master of Science)