title: Photolytic and photocatalytic degradation of the antipsychotic agent tiapride: Kinetics, transformation pathways and computational toxicity assessment.
abstract: The photolytic and photocatalytic transformation of tiapride with the use of TiO2and H2O2was investigated. A novel micro-scale method for simultaneous irradiation with simulated full solar spectrum of multiple samples in photostability chamber was proposed. RP-UHPLC-DAD coupled with ESI-Q-TOF mass spectrometer was used for the quantitative and qualitative analysis of the processes. Quantitative method was fully validated, and kinetic parameters of tiapride photodegradation were compared. Structures of twenty-one photoproducts as well as phototransformation pathways were proposed. Based on the elucidated structures, computational toxicity assessment with the use of various software was performed and some of transformation products were found as a potentially highly mutagenic and carcinogenic compounds. The multivariate statistical method (principal component analysis) was used to compare toxicity of phototransformation products as well as toxicity assessment.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland. Electronic address: jakub.trawinski@umlub.pl.
authors.forename: Jakub
authors.initials: J
authors.lastname: Trawiński
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
authors.forename: Robert
authors.initials: R
authors.lastname: Skibiński
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D059001:Aquatic Organisms; D002273:Carcinogens / Q000633:toxicity; D002384:Catalysis; D003621:Daphnia; D005399:Fishes; D006861:Hydrogen Peroxide / Q000737:chemistry; D007700:Kinetics; D007928:Lethal Dose 50; D051379:Mice; D009153:Mutagens / Q000633:toxicity; D010777:Photochemistry; D010782:Photolysis; D025341:Principal Component Analysis; D051381:Rats; D012015:Reference Standards; D013472:Sunlight; D063325:Tiapride Hydrochloride / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*; D014025:Titanium / Q000737:chemistry
chemical_list: D014150:Antipsychotic Agents; D002273:Carcinogens; D009153:Mutagens; C009495:titanium dioxide; D063325:Tiapride Hydrochloride; D006861:Hydrogen Peroxide; D014025:Titanium
keywords: Computational toxicity; LC–MS; Photocatalysis; Photolysis; Tiapride