Use of UPLC-HRMS/MS for In Vitro and In Vivo Metabolite Identification of Three Methylphenidate-derived New Psychoactive Substances
| Autor: | Sascha K. Manier, Sophia Niedermeier, Jan Schäper, Markus R. Meyer |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
Health Toxicology and Mutagenesis Metabolite Urine Toxicology Tandem mass spectrometry 01 natural sciences High-performance liquid chromatography Designer Drugs Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Tandem Mass Spectrometry In vivo Animals Humans Environmental Chemistry Toxicokinetics Screening procedures Psychotropic Drugs Chemical Health and Safety Chromatography Chemistry 010401 analytical chemistry Rats 0104 chemical sciences Substance Abuse Detection S9 fraction Methylphenidate 030217 neurology & neurosurgery Chromatography Liquid |
| Zdroj: | Journal of Analytical Toxicology. 44:156-162 |
| ISSN: | 1945-2403 0146-4760 |
| Popis: | The distribution of so-called new psychoactive substances (NPS) as substitute for common drug of abuse was steadily increasing in the last years, but knowledge about their toxicodynamic and toxicokinetic properties is lacking. However, a comprehensive knowledge of their toxicokinetics, particularly their metabolism, is crucial for developing reliable screening procedures and to verify their intake, e.g., in case of intoxications. The aim of this study was therefore to tentatively identify the metabolites of the methylphenidate-derived NPS isopropylphenidate (isopropyl 2-phenyl-2-(2-piperidyl) acetate, IPH), 4-fluoromethylphenidate (methyl 2-(4-fluorophenyl)-2-(piperidin-2-yl) acetate, 4-FMPH) and 3,4-dichloromethylphenidate (methyl 2-(3,4-dichlorophenyl)-2-(piperidin-2-yl) acetate, 3,4-CTMP) using different in vivo and in vitro techniques and ultra-high performance liquid chromatography–high-resolution mass spectrometry (UHPLC-HRMS/MS). Urine samples of male rats were analyzed, and the transfer to human metabolism was done by using pooled human S9 fraction (pS9), which contains the microsomal fraction of liver homogenisate as well as its cytosol. UHPLC-HRMS/MS analysis of rat urine revealed 17 metabolites for IPH (14 phase I and 3 phase II metabolites), 13 metabolites were found for 4-FMPH (12 phase I metabolites and 1 phase II metabolite) and 7 phase I metabolites and no phase II metabolites were found for 3,4-CTMP. pS9 incubations additionally indicated that all investigated substances were primarily hydrolyzed, resulting in the corresponding carboxy metabolites. Finally, these carboxy metabolites should be used as additional analytical targets besides the parent compounds for comprehensive mass spectrometry–based screening procedures. |
| Databáze: | OpenAIRE |
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