Distribution of Synthetic Cannabinoids JWH-210, RCS-4 and Δ 9-Tetrahydrocannabinol After Intravenous Administration to Pigs.
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.
Institute of Legal Medicine, Saarland University, Building 80.2, D-66421 Homburg (Saar). Germany.
Nadine
N
Schaefer
Institute of Legal Medicine, Saarland University, Building 80.2, D-66421 Homburg (Saar). Germany.
Mattias
M
Kettner
Institute for Clinical & Experimental Surgery, Saarland University, D-66421 Homburg (Saar). Germany.
Matthias W
MW
Laschke
Institute of Legal Medicine, Saarland University, Building 80.2, D-66421 Homburg (Saar). Germany.
Julia
J
Schlote
Institute of Legal Medicine, Saarland University, Building 80.2, D-66421 Homburg (Saar). Germany.
Andreas H
AH
Ewald
Institute for Clinical & Experimental Surgery, Saarland University, D-66421 Homburg (Saar). Germany.
Michael D
MD
Menger
Department of Experimental and Clinical Toxicology, Saarland University, Building 46 D-66421 Homburg (Saar). Germany.
Hans H
HH
Maurer
Institute of Legal Medicine, Saarland University, Building 80.2, D-66421 Homburg (Saar). Germany.
Peter H
PH
Schmidt
D061605:Administration, Intravenous; D000818:Animals; D001921:Brain / Q000378:metabolism; D002186:Cannabinoids / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D013759:Dronabinol / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D007211:Indoles / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D009281:Naphthalenes / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics*; D016658:Psoas Muscles / Q000378:metabolism; D013154:Spleen / Q000378:metabolism; D013552:Swine; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
C000613875:2-(4-methoxyphenyl)-1-(1-pentyl-indol-3-yl)methanone; C582338:4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone; D002186:Cannabinoids; D007211:Indoles; D009281:Naphthalenes; D013759:Dronabinol
LC-MS/MS; Synthetic cannabinoids; pharmacokinetics; pigs; tetrahydrocannabinol; tissue distribution