Title:Distribution of Synthetic Cannabinoids JWH-210, RCS-4 and Δ 9-Tetrahydrocannabinol After Intravenous Administration to Pigs
Volume: 15
Issue: 5
Author(s): Nadine Schaefer*, Mattias Kettner, Matthias W. Laschke, Julia Schlote, Andreas H. Ewald, Michael D. Menger, Hans H. Maurer and Peter H. Schmidt
Affiliation:
- Institute of Legal Medicine, Saarland University, Building 80.2, D-66421 Homburg (Saar),Germany
Keywords:
Synthetic cannabinoids, tetrahydrocannabinol, pigs, tissue distribution, LC-MS/MS, pharmacokinetics
Abstract: Background: Synthetic cannabinoids (SCs) have become an increasing issue in forensic
toxicology. Controlled human studies evaluating pharmacokinetic data of SCs are lacking and only
few animal studies have been published. Thus, an interpretation of analytical results found in
intoxicated or poisoned individuals is difficult. Therefore, the distribution of two selected SCs, namely
4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210) and 2-(4-methoxyphenyl)-1-(1-
pentyl-indol-3-yl)methanone (RCS-4) as well as Δ9-tetrahydrocannabinol (THC) as reference were
examined in pigs.
Methods: Pigs (n = 6 per drug) received a single intravenous 200 μg/kg BW dose of JWH-210, RCS-
4, or THC. Six hours after administration, the animals were exsanguinated and relevant organs,
important body fluids such as bile, and tissues such as muscle and adipose tissue, as well as the
bradytrophic specimens dura and vitreous humor were collected. After hydrolysis and solid phase
extraction, analysis was performed by LC-MS/MS. To overcome matrix effects of the LC-MS/MS
analysis, a standard addition method was applied for quantification.
Results: The parent compounds could be detected in every analyzed specimen with the exception of
THC that was not present in dura and vitreous humor. Moderate concentrations were present in brain,
the site of biological effect. Metabolite concentrations were highest in tissues involved in metabolism
and/or elimination
Conclusions: Besides kidneys and lungs routinely analyzed in postmortem toxicology, brain, adipose,
and muscle tissue could serve as alternative sources, particularly if other specimens are not available.
Bile fluid is the most appropriate specimen for SCs and THC metabolites detection.
