title: Understanding the degradation of electrochemically-generated reactive drug metabolites by quantitative NMR.
abstract: Phenacetin is known to be metabolized to N-AcetylParaBenzoQuinoneImine (NAPQI), which is a common metabolite of paracetamol (also called acetaminophen or APAP). The electrochemical conversion of APAP to NAPQI was shown in 1989 by Getek and co-workers, thus demonstrating the capacity of electrochemistry to mimic the formation of NAPQI from APAP as well as from phenacetin. This study focuses on a preparative electrochemical electrolysis associated with quantitative (1)H NMR. On one hand, this method is able to synthesize reactive metabolites in sufficient concentrations and amounts for NMR analysis. On the other hand, NMR allows the simultaneous detection and quantification of all chemical species, in contrast to mass spectrometry. The combination of electrochemistry with quantitative NMR is thus presented as a relevant method for elucidating the degradation of reactive metabolites and may be considered a valuable complementary tool to EC-MS.
authors.affiliation: LUNAM Université de Nantes, CNRS, Chimie et Interdisciplinarité: Synthèse, Analyse et Modélisation (CEISAM), UMR 6230, 2 rue de la Houssinière, BP 92208, F-44322 Nantes cedex 3, France. Electronic address: ugo.bussy@univ-nantes.fr.
authors.forename: Ugo
authors.initials: U
authors.lastname: Bussy
authors.forename: Patrick
authors.initials: P
authors.lastname: Giraudeau
authors.forename: Illa
authors.initials: I
authors.lastname: Tea
authors.forename: Mohammed
authors.initials: M
authors.lastname: Boujtita
mesh_terms: D000082:Acetaminophen / Q000032:analysis* / Q000737:chemistry; D016227:Benzoquinones / Q000032:analysis* / Q000737:chemistry; D001711:Biotransformation; D004572:Electrolysis; D006801:Humans; D007097:Imines / Q000032:analysis* / Q000737:chemistry; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods*; D010615:Phenacetin / Q000032:analysis* / Q000737:chemistry; D012996:Solutions
chemical_list: D016227:Benzoquinones; D007097:Imines; D012996:Solutions; D000082:Acetaminophen; D010615:Phenacetin; C028473:N-acetyl-4-benzoquinoneimine
keywords: Degradation; Electrochemistry; Phenacetin; Quantitative NMR; Quinone imine