Diphenidine, a new psychoactive substance: metabolic fate elucidated with rat urine and human liver preparations and detectability in urine using GC-MS, LC-MSn, and LC-HR-MSn
| Autor: | Julian A. Michely, Carina S. D. Wink, Hans H. Maurer, Andrea Jacobsen-Bauer, Josef Zapp |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chromatography Urinalysis medicine.diagnostic_test medicine.drug_class Chemistry Diphenidine 010401 analytical chemistry Glucuronidation Forensic toxicology CYP1A2 Pharmaceutical Science Urine 01 natural sciences 0104 chemical sciences Analytical Chemistry Designer drug 03 medical and health sciences 030104 developmental biology medicine Environmental Chemistry Gas chromatography–mass spectrometry Spectroscopy |
| Zdroj: | Drug Testing and Analysis. 8:1005-1014 |
| ISSN: | 1942-7603 |
| Popis: | Diphenidine is a new psychoactive substance (NPS) sold as a 'legal high' since 2013. Case reports from Sweden and Japan demonstrate its current use and the necessity of applying analytical procedures in clinical and forensic toxicology. Therefore, the phase I and II metabolites of diphenidine should be identified and based on these results, the detectability using standard urine screening approaches (SUSAs) be elucidated. Urine samples were collected after administration of diphenidine to rats and analyzed using different sample workup procedures with gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-(high resolution)-mass spectrometry (LC-(HR)-MS). With the same approaches incubates of diphenidine with pooled human liver microsomes (pHLM) and cytosol (pHLC) were analyzed. According to the identified metabolites, the following biotransformation steps were proposed in rats: mono- and bis-hydroxylation at different positions, partly followed by dehydrogenation, N,N-bis-dealkylation, and combinations of them followed by glucuronidation and/or methylation of one of the bis-hydroxy-aryl groups. Mono- and bis-hydroxylation followed by dehydrogenation could also be detected in pHLM or pHLC. Cytochrome-P450 (CYP) isozymes CYP1A2, CYP2B6, CYP2C9, and CYP3A4 were all capable of forming the three initial metabolites, namely hydroxy-aryl, hydroxy-piperidine, and bis-hydroxy-piperidine. In incubations with CYP2D6 hydroxy-aryl and hydroxy-piperidine metabolites were detected. After application of a common users' dose, diphenidine metabolites could be detected in rat urine by the authors' GC-MS as well as LC-MSn SUSA. Copyright © 2016 John Wiley & Sons, Ltd. |
| Databáze: | OpenAIRE |
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