title: Electrochemical oxidation by square-wave potential pulses in the imitation of phenacetin to acetaminophen biotransformation.
abstract: Electrochemistry in combination with mass spectrometry is emerging as a versatile analytical technique in the imitation of oxidative drug metabolism during the early stages of drug discovery and development. Here, we present electrochemical O-dealkylation of phenacetin to acetaminophen by square-wave potential pulses consisting of consecutive sub-second oxidation and reduction steps. This O-dealkylation could not be achieved by oxidation at constant potential or longer potential pulses because of the fast hydrolysis of the reactive intermediates. Electrochemical conversion by square-wave potential pulses can thus widen the scope of electrochemical synthesis of metabolites and imitation of in vivo drug metabolism.
authors: Analytical Biochemistry and Mass Spectrometry Core Facility, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors: Eslam
authors: E
authors: Nouri-Nigjeh
authors: Rainer
authors: R
authors: Bischoff
authors: Andries P
authors: AP
authors: Bruins
authors: Hjalmar P
authors: HP
authors: Permentier
mesh_terms: D000082:Acetaminophen / Q000737:chemistry* / Q000378:metabolism; D001711:Biotransformation; D003640:Dealkylation; D055808:Drug Discovery / Q000379:methods; D055664:Electrochemical Techniques / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods; D010084:Oxidation-Reduction; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010615:Phenacetin / Q000737:chemistry* / Q000378:metabolism
chemical_list: D004364:Pharmaceutical Preparations; D000082:Acetaminophen; D010615:Phenacetin