title: Comparison of TiO2 photocatalysis, electrochemically assisted Fenton reaction and direct electrochemistry for simulation of phase I metabolism reactions of drugs.
abstract: The feasibility of titanium dioxide (TiO2) photocatalysis, electrochemically assisted Fenton reaction (EC-Fenton) and direct electrochemical oxidation (EC) for simulation of phase I metabolism of drugs was studied by comparing the reaction products of buspirone, promazine, testosterone and 7-ethoxycoumarin with phase I metabolites of the same compounds produced in vitro by human liver microsomes (HLM). Reaction products were analysed by UHPLC-MS. TiO2 photocatalysis simulated the in vitro phase I metabolism in HLM more comprehensively than did EC-Fenton or EC. Even though TiO2 photocatalysis, EC-Fenton and EC do not allow comprehensive prediction of phase I metabolism, all three methods produce several important metabolites without the need for demanding purification steps to remove the biological matrix. Importantly, TiO2 photocatalysis produces aliphatic and aromatic hydroxylation products where direct EC fails. Furthermore, TiO2 photocatalysis is an extremely rapid, simple and inexpensive way to generate oxidation products in a clean matrix and the reaction can be simply initiated and quenched by switching the UV lamp on/off.
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland. Electronic address: miina.ruokolainen@helsinki.fi.
authors.forename: Miina
authors.initials: M
authors.lastname: Ruokolainen
authors.affiliation: Analytical Biochemistry, Department of Pharmacy, University of Groningen, A Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: t.gul@rug.nl.
authors.forename: Turan
authors.initials: T
authors.lastname: Gul
authors.affiliation: Analytical Biochemistry, Department of Pharmacy, University of Groningen, A Deusinglaan 1, 9713 AV Groningen, The Netherlands. Electronic address: h.p.permentier@rug.nl.
authors.forename: Hjalmar
authors.initials: H
authors.lastname: Permentier
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland. Electronic address: tiina.sikanen@helsinki.fi.
authors.forename: Tiina
authors.initials: T
authors.lastname: Sikanen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland. Electronic address: risto.kostiainen@helsinki.fi.
authors.forename: Risto
authors.initials: R
authors.lastname: Kostiainen
authors.affiliation: Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5E), FI-00014, Finland; Laboratory of Analytical Chemistry, Department of Chemistry, University of Helsinki, P.O. BOX 55 (A.I. Virtasen aukio 1), FI-00014, Finland. Electronic address: tapio.kotiaho@helsinki.fi.
authors.forename: Tapio
authors.initials: T
authors.lastname: Kotiaho
mesh_terms: D002065:Buspirone / Q000737:chemistry* / Q000378:metabolism; D002384:Catalysis; D003374:Coumarins / Q000737:chemistry* / Q000378:metabolism; D003640:Dealkylation; D004563:Electrochemistry; D006801:Humans; D006865:Hydrogenation; D006900:Hydroxylation; D007501:Iron / Q000737:chemistry; D008862:Microsomes, Liver / Q000378:metabolism; D010084:Oxidation-Reduction; D011395:Promazine / Q000737:chemistry* / Q000378:metabolism; D013739:Testosterone / Q000737:chemistry* / Q000378:metabolism; D014025:Titanium / Q000737:chemistry* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D003374:Coumarins; C009495:titanium dioxide; C017299:7-ethoxycoumarin; D013739:Testosterone; D014025:Titanium; D007501:Iron; D011395:Promazine; D002065:Buspirone
keywords: Electrochemistry; Fenton reaction; Liquid chromatography–mass spectrometry; Metabolism; Simulation; Titanium dioxide photocatalysis