title: Determination of psychostimulants and their metabolites by electrochemistry linked on-line to flowing atmospheric pressure afterglow mass spectrometry.
abstract: The flowing atmospheric pressure afterglow (FAPA) ion source operates in the ambient atmosphere and has been proven to be a promising tool for direct and rapid determination of numerous compounds. Here we linked a FAPA-MS system to an electrochemical flow cell for the identification of drug metabolites generated electrochemically in order to study simulated metabolic pathways. Psychostimulants and their metabolites produced by electrochemistry (EC) were detected on-line by FAPA-MS. The FAPA source has never been used before for an on-line connection with liquid flow, neither for identification of products generated in an electrochemical flow cell. The system was optimized to achieve the highest ionization efficiency by adjusting several parameters, including distances and angles between the ion source and the outlet of the EC system, the high voltage for plasma generation, flow-rates, and EC parameters. Simulated metabolites from tested compounds [methamphetamine (MAF), para-methoxy-N-methylamphetamine (PMMA), dextromethorphan (DXM), and benzydamine (BAM)] were formed in the EC cell at various pH levels. In all cases the main products were oxidized substrates and compounds after N-demethylation. Generation of such products and their thorough on-line identification confirm that the cytochrome P450 - driven metabolism of pharmaceuticals can be efficiently simulated in an electrochemical cell; this approach may serve as a step towards predictive pharmacology using a fast and robust design.
authors.affiliation: Department of Biochemistry and Neurobiology, Faculty of Materials Science and Ceramics, AGH-University of Science and Technology, Mickiewicza 30, 30-059 Krakow, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Smoluch
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Mielczarek
authors.forename: Edward
authors.initials: E
authors.lastname: Reszke
authors.forename: Gary M
authors.initials: GM
authors.lastname: Hieftje
authors.forename: Jerzy
authors.initials: J
authors.lastname: Silberring
mesh_terms: D000893:Anti-Inflammatory Agents / Q000032:analysis* / Q000378:metabolism; D001274:Atmospheric Pressure; D001591:Benzydamine / Q000032:analysis* / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000032:analysis* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003915:Dextromethorphan / Q000032:analysis* / Q000378:metabolism; D055664:Electrochemical Techniques / Q000295:instrumentation; D004867:Equipment Design; D018691:Excitatory Amino Acid Antagonists / Q000032:analysis* / Q000378:metabolism; D006801:Humans; D013058:Mass Spectrometry / Q000295:instrumentation*; D053858:Metabolic Networks and Pathways; D008694:Methamphetamine / Q000031:analogs & derivatives / Q000032:analysis* / Q000378:metabolism; D008745:Methylation; D010084:Oxidation-Reduction
chemical_list: D000893:Anti-Inflammatory Agents; D000697:Central Nervous System Stimulants; D018691:Excitatory Amino Acid Antagonists; D008694:Methamphetamine; D001591:Benzydamine; D003915:Dextromethorphan; D003577:Cytochrome P-450 Enzyme System