Abstract
New psychoactive substances, especially synthetic cannabinoids (SC), are gaining increasing relevance in postmortem forensic toxicology. Particularly, the interpretation of analytical results is challenging, as usually, no toxicokinetic (TK) data concerning distribution in organs and tissues are available. Thus, a controlled pig TK study allowing for examination of organ and tissue distribution of SC was performed. For this purpose, 12 pigs received a single pulmonary dose of 200 µg/kg body weight each of 4-ethylnaphthalene-1-yl-(1-pentylindole-3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1-pentylindole-3-yl)methanone (RCS-4), and Δ9-tetrahydrocannabinol (THC) via an ultrasonic nebulizer. Eight hours after administration, the animals were put to death by the administration of T61. Thereupon, relevant organs, important body fluids such as bile and colon content, and tissues such as muscle tissue were collected. After enzymatic hydrolysis and solid-phase extraction, analysis was performed by liquid chromatography–tandem mass spectrometry. For quantification, a standard addition method was applied. The parent compounds could be detected in every analyzed specimen with the exception of colon content. Regarding JWH-210, the kidneys and lungs are viable matrices for postmortem analysis. In terms of RCS-4, the lungs were found to be an appropriate matrix. Concerning THC, the liver, bile fluid as well as duodenum content were suitable matrices for detection. Metabolites were only detected in tissues/body fluids involved in metabolism and/or elimination. Bile fluid and duodenum content were shown, as the most appropriate specimens for quantification of metabolites.
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Acknowledgements
The authors thank Benjamin Peters and the staff of the Institute for Clinical & Experimental Surgery at Saarland University for their support and help during the study as well as the Saarland University for the research grant (Anschubfinanzierung von Forschungsprojekten, 61-cl/Anschub 2017/bew-Schäfer).
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All experiments were performed in accordance with the German legislation on protection of animals and the National Institutes of Health Guide for the Care and Use of Laboratory Animals (permission number: 69/2013).
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Schaefer, N., Kröll, AK., Körbel, C. et al. Distribution of the (synthetic) cannabinoids JWH-210, RCS-4, as well as ∆9-tetrahydrocannabinol following pulmonary administration to pigs. Arch Toxicol 93, 2211–2218 (2019). https://doi.org/10.1007/s00204-019-02493-8
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DOI: https://doi.org/10.1007/s00204-019-02493-8