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Metabolic profiling of four synthetic stimulants,including the novel indanyl-cathinone 5-PPDi,after human hepatocyte incubation

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Journal of Pharmaceutical Analysis 2020年第2期10卷 147-156页

作者： David Fabregat-Safont Marie Mardal Juan V.Sancho Félix Hernández kristian linnet María Ibánez Research Institute for Pesticides and Water University Jaume IAvda.Sos Baynat s/n12071CastellónSpain Department of Forensic Medicine Section of Forensic ChemistryFaculty of Health and Medicinal SciencesUniversity of CopenhagenFrederik V's vej 112100KФbenhavnФDenmark Department of Occupational and Environmental Medicine University Hospital of Northern NorwaySykehusvegenTromsoeNorway

Synthetic cathinones are new psychoactive substances that represent a health risk worldwide.For most of the 130 reported compounds,information about toxicology and/or metabolism is not available,which hampers their detection(and subsequent medical treatment)in intoxication cases.The principles of forensic analytical chemistry and the use of powerful analytical techniques are indispensable for stab-lishing the most appropriate biomarkers for these substances.Human metabolic fate of synthetic cathinones can be assessed by the analysis of urine and blood obtained from authentic consumers;however,this type of samples is limited and difficult to access.In this work,the metabolic behaviour of three synthetic cathinones(4-CEC,4-CPrC and 5-PPDi)and one amphetamine(3-FEA)has been evalu-ated by incubation with pooled human hepatocytes and metabolite identification has been performed by high-resolution mass spectrometry.This in vitro approach has previously shown its feasibility for obtaining excretory human metabolites.4-CEC and 3-FEA were not metabolised,and for 4-CPrC only two minor metabolites were obtained.On the contrary,for the recently reported 5-PPDi,twelve phase I metabolites were elucidated.Up to our knowledge,this is the first metabolic study of an indanyl-cathinone.Data reported in this paper will allow the detection of these synthetic stimulants in intoxi-cation cases,and will facilitate future research on the metabolic behaviour of other indanyl-based cathinones.

关键词： Synthetic cathinones 5-PPDi Metabolite identification In vitro metabolism Hepatocyte incubation High resolution mass spectrometry

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