Background: Since their appearance on the drugs of abuse market, synthetic cannabinoids
(SCs) are gaining increasing toxicological relevance. They are consumed without knowledge of their
toxicokinetic (TK) and toxicodynamic properties and human studies are not allowed due to ethical reasons.
A controlled animal TK study following nebulization of 4-ethylnaphthalene-1-yl-(1-pentylindole-
3-yl)methanone (JWH-210), 2-(4-methoxyphenyl)-1-(1-pentyl-indole-3-yl)methanone (RCS-4) as well
as Δ9-tetrahydrocannabinol (THC) to pigs should be helpful for better interpretation of analytical results
in cases of misuse or poisoning. As a prerequisite, an in-vitro test system mimicking a ventilated
pig had to be developed to determine the quantity and reproducibility of which drug dose is delivered to
the pig lung.
Methods: JWH-210, RCS-4, and THC (1 mg in 2 mL ethanol each) were nebulized during ventilation
using an ultrasonic nebulizer. The drug aerosol was delivered via the inspiratory limb and the endotracheal
tube passing through a glass fiber filter (n = 6). The drugs were extracted from the filters using
ethanol and ultrasonication. After several dilution steps and adding an internal standard solution, the
extracts were analyzed by LC-MS/MS.
Results: Extraction of the nebulized drugs revealed delivery efficiencies of 78.8 ± 5.0% for JWH-210,
70.5 ± 6.9% for RCS-4, and 70.8 ± 7.9% for THC. The loss of about 20-30% of the administered dose
might be attributable to retention in the nebulizer device or adhesion of the aerosol particles to the tube
Conclusion: Nevertheless, regarding delivery efficiencies, the minor standard deviations indicate an
acceptable reproducibility, suggesting that this administration system is suitable for application in TK