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Erschienen in: Forensic Toxicology 1/2020

10.10.2019 | Original Article

In vivo and in vitro metabolism of the novel synthetic cannabinoid 5F-APINAC

verfasst von: Svetlana A. Appolonova, Covadonga Palacio, Ksenia M. Shestakova, Natalia V. Mesonzhnik, Alex Brito, Roman M. Kuznetsov, Pavel A. Markin, Natalia L. Bochkareva, Dmitry Burmykin, Maxim Ovcharov, Giacomo Musile, Franco Tagliaro, Sergey A. Savchuk

Erschienen in: Forensic Toxicology | Ausgabe 1/2020

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Abstract

Purpose

New generations of synthetic cannabinoids (SCs) have recognized strong psychoactive effects, rapidly becoming potent drugs of abuse. Characterization of metabolites associated with SCs is useful for their subsequent detection in biological samples. We aimed to investigate the metabolism of 5F-APINAC, a novel SC, in human liver microsomes (HLMs) (in vitro) and in a rat model (in vivo).

Methods

For the in vitro study, the standard solution of 5F-APINAC was incubated with HLMs for 1 h at 37 °C. In the in vivo study, rats received 15 mg/kg of 5F-APINAC diluted in ethanol or in dimethyl sulfoxide, while a vehicle control group received placebo. Urine was collected 3, 6, and 24 h after administration. The metabolic characterization was performed using liquid chromatography–ion trap mass spectrometry and liquid chromatography–quadrupole time-of-flight mass spectrometry.

Results

In total, 15 metabolites associated with 5F-APINAC were tentatively identified. The metabolites were classified as: 1-adamantol metabolites, oxidative defluorination metabolites, and N-fluoropentylindazole-3-carboxylic acid metabolites. The modifications included ester hydrolysis, mono-, di-, and trihydroxylation of adamantyl ring and N-fluoropentylindazole moiety, oxidation (carbonyl formation) of the N-fluoropentyl side chain, oxidative loss of fluorine, and glucuronidation, as well as combinations thereof. The predominant metabolic reaction was ester hydrolysis in both in vitro and in vivo experiments and formation of M9 (5-fluoropentylindazole-3-carboxylic acid). However, the most recommendable metabolites for proving 5F-APINAC consumption in urine were M4.1, M7, and M13. No metabolites were detected in rat’s urine 24 h after drug administration.

Conclusions

The discovered metabolites are proposed to be incorporated into routine screening analytical methods as the urine markers of 5F-APINAC consumption. This is the first report to demonstrate the metabolism of 5F-APINAC to our knowledge.
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Metadaten
Titel
In vivo and in vitro metabolism of the novel synthetic cannabinoid 5F-APINAC
verfasst von
Svetlana A. Appolonova
Covadonga Palacio
Ksenia M. Shestakova
Natalia V. Mesonzhnik
Alex Brito
Roman M. Kuznetsov
Pavel A. Markin
Natalia L. Bochkareva
Dmitry Burmykin
Maxim Ovcharov
Giacomo Musile
Franco Tagliaro
Sergey A. Savchuk
Publikationsdatum
10.10.2019
Verlag
Springer Singapore
Erschienen in
Forensic Toxicology / Ausgabe 1/2020
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI
https://doi.org/10.1007/s11419-019-00503-z

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