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2009-06-06 - Colloque/Présentation - communication orale - Anglais - 1 page(s)

Hambye Stéphanie , Kauffmann Jean-Michel, Blankert Bertrand , "“On-line electrochemistry/mass spectrometry: tools of high potentiality for predictive drug biotransformation studies.”" in Pre-satellite meeting PharmSciFair '09 (Young Pharmaceutical Scientists), Nice, France, 2009

  • Codes CREF : Analyse et contrôle pharmaceutique (DI3450), Chimie analytique (DI1314), Sciences pharmaceutiques (DI3400), Métabolisme (DI3223)
  • Unités de recherche UMONS : Analyse pharmaceutique (M130)
  • Instituts UMONS : Institut des Sciences et Technologies de la Santé (Santé)

Abstract(s) :

(Anglais) The development of newer and sound bioanalytical methods dedicated to the process of drug discovery and development, will contribute to overcome the crucial point constituted by stopping the development of unsuitable drug candidates at early stages of the selection process. Thanks to the possibility to combine on-line an electrochemical cell and a mass spectrometer (eventually completed and improved with a separation step), accurate identification of oxidation products is achieved1. We illustrate the potential of on-line combination of EC-MS studies in the pharmaceutical era by studying the complex in vitro electrooxidation of several neuroleptics, namely structurally related phenothiazines and clozapine. This study permitted to postulate a general oxidation mechanism for phenothiazines depending on the structure of their lateral chain2. In the case of clozapine (a dibenzoazepine), several (but not all) phase I and phase II metabolites were identified. Of additional special interest, this set up allows for the study of the oxidation of these molecules in the presence of thiols (glutathione, cysteine etc…) and identification of nucleophilic substitution3. The really high capacity to mimic partially the CYP450 system as well as for metabolites identifications than for glutathione adducts recognition, confers to the described hyphenated system a promising future. 1. Gamache, P.; Smith, R.; McCarthy, R.; Waraska, J. and Acworth, I.,Spectroscopy, 18 (2003) 14 - 41 2. Blankert, B.; Hayen, H.; van Leeuwen, S.M.; Karst, U.; Bodoki, E.; Lotrean, S.; Sandulescu, R.; Mora Diez, N.; Dominguez, O.; Arcos, J. and Kauffmann, J.-M. Electroanalysis, 17 (2005) 1501 - 1510, 3. Van Leeuwen, S.M.; Blankert, B.; Kauffmann, J.-M. and Karst, U., Anal. Bioanal. Chem., 382 (2005) 742 - 750.