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Metabolic and pharmacokinetic characterization of a new synthetic cannabinoid APINAC in rats

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Abstract

Purpose

Adamantan-1-yl 1-pentyl-1H-indazole-3-carboxylate (APINAC), a new synthetic cannabinoid, was recently isolated from a dietary supplement and identified in our laboratories. The metabolism and pharmacokinetics of APINAC were studied in vitro and in vivo with a rat model.

Methods

APINAC (2.0 μM) was incubated with rat liver microsomes (RLMs) for up to 90 min to determine its phase I metabolic profile. APINAC was also administered to rats at a dose of 5 mg/kg intravenously (i.v.) or 10 mg/kg per os (p.o.). Blood samples were collected at specific time points, and urine samples were also collected for 1 day following APINAC administration. The analyses were conducted by both high- and low-resolution liquid chromatography–tandem mass spectrometry.

Results

Although APINAC was rapidly metabolized by RLMs (t 1/2, 15.2 ± 0.4 min), in vivo pharmacokinetic experiments in rats revealed moderate to long half-lives [11.3 h (i.v.) and 3.8 h (p.o.)]. A total of 22 APINAC metabolites could be detected in the RLMs and rat urine. APINAC was predominantly metabolized via ester hydrolysis to carboxylic acids M1 (with hydroxylation) and M18 (without hydroxylation), representative markers for APINAC intake. Hydroxylation of APINAC, with or without subsequent oxidation and glucuronidation, was observed in the case of the other metabolites.

Conclusions

The diagnosis of illegal APINAC intake can be realized through the detection of several characteristic APINAC metabolites in human urine and/or APINAC itself in blood.

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Acknowledgements

This research was supported by a research grant (15182MFDS523) from the Ministry of Food and Drug Safety (MFDS) in Korea and by research grants from Kangwon National University. We thank the Central Laboratory of Kangwon National University for providing technical assistance with the spectroscopic experiments.

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Authors and Affiliations

  1. College of Pharmacy, Kangwon National University, 1 Kangwondaehak-gil, Chuncheon, Gangwon-do, 24341, Republic of Korea

    Jungjoong Hwang, Jiho Hwang, Bogonda Ganganna, Insuk Song, Moon Young Heo, Sung-Hoon Ahn & Jongkook Lee

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  1. Jungjoong Hwang
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  2. Jiho Hwang
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  3. Bogonda Ganganna
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  4. Insuk Song
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  7. Jongkook Lee
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Correspondence to Jongkook Lee.

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The authors declare that they have no conflict of interest.

Ethical approval

This article does not describe any studies that include human participants performed by any of the authors. All experimental protocols involving the animals in this study were approved by the Institutional Animal Care and Use Committee of Kangwon National University (permit number: KW-161219-2).

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Hwang, J., Hwang, J., Ganganna, B. et al. Metabolic and pharmacokinetic characterization of a new synthetic cannabinoid APINAC in rats. Forensic Toxicol 36, 88–101 (2018). https://doi.org/10.1007/s11419-017-0387-4

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  • DOI: https://doi.org/10.1007/s11419-017-0387-4

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