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27.05.2020 | Original Article

In vitro metabolic profiles of adamantyl positional isomers of synthetic cannabinoids

verfasst von: Natsuki Kadomura, Tetsuro Ito, Hidenobu Kawashima, Takaya Matsuhisa, Tomoe Kinoshita, Midori Soda, Erina Kohyama, Takaharu Iwaki, Hiroyuki Nagai, Kiyoyuki Kitaichi

Erschienen in: Forensic Toxicology | Ausgabe 1/2021

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Abstract

Purpose

Illegal use of synthetic cannabinoids (SCs) is a serious problem worldwide. Legal regulation of SCs requires fundamental analytical studies regarding the differentiation of potential structural isomers. Accumulation of SC metabolic profiles is also essential for forensic investigation because SCs are immediately metabolized after intake. Thus, we investigated the in vitro metabolism of N-adamantyl-1-(tetrahydropyran-4-ylmethyl)-1H-indazole-3-carboxamide isomers (ATHs) using human liver microsomes (HLMs). Moreover, we validated the applicability of the isomeric differentiation by investigation of N-adamantyl-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide isomers (AFUs).

Methods

Metabolites were collected at designated time points during the incubation period with HLMs for up to 180 min. The structures of the metabolites were annotated on the basis of mass spectroscopic evidence obtained by liquid chromatography–ion trap–time of flight mass spectrometry.

Results

The secondary stage mass (MS2) spectra obtained from the protonated molecules revealed a clear difference in both ATHs and their major metabolites because of the stability of the adamantyl (AD) cation. In HLMs, ATHs were quickly metabolized, and hydroxylation of the AD ring was deduced as the major metabolic pathway. The major metabolites of ATH 1 and ATH 2 after 180 min showed dihydroxylation and monohydroxylation of the AD ring. The AFUs showed analytical and metabolic profiles similar to those of the ATHs described above.

Conclusions

We characterized the metabolism of ATHs for the first time and discriminated between the two isomers by mass spectrometric analysis of either the parent compounds or their major metabolites. Our investigation of AFUs also demonstrated a useful method for distinguishing between AD isomers.

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Titel: In vitro metabolic profiles of adamantyl positional isomers of synthetic cannabinoids
verfasst von: Natsuki Kadomura
Tetsuro Ito
Hidenobu Kawashima
Takaya Matsuhisa
Tomoe Kinoshita
Midori Soda
Erina Kohyama
Takaharu Iwaki
Hiroyuki Nagai
Kiyoyuki Kitaichi
Publikationsdatum: 27.05.2020
Verlag: Springer Singapore
Erschienen in: Forensic Toxicology / Ausgabe 1/2021
Print ISSN: 1860-8965
Elektronische ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-020-00538-7

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In vitro metabolic profiles of adamantyl positional isomers of synthetic cannabinoids

Abstract

Purpose

Methods

Results

Conclusions

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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