Effects of lipophilicity and functional groups of synthetic cannabinoids on their blood concentrations and urinary excretion

•Fifteen synthetic cannabinoids (SCs) were determined in the urine or blood from 31 SC users who were involved in car crashes.•Lipophilic SCs were not detected in urine while water-soluble SCs were often detected.•Range of lipophilic SCs concentrations in blood were much narrower than that of water-soluble SCs concentrations.•Concentrations SCs with a terminal ester moiety were much lower than those of SCs with a terminal amide moiety. The influence of lipophilicity and functional groups of synthetic cannabinoids (SCs) on their blood concentrations and urinary excretion has been studied by analyzing blood and urine specimens sampled from drivers who were involved in a car crashes under the influence of SCs. A total of 58 specimens (26 urine and 31 blood specimens), sampled within 13h of the occurrence, were analyzed by liquid chromatography-tandem mass spectrometry. Fifteen SCs were detected in those specimens; the SCs detected were categorized as follows: Class 1, Naphthoyl/Benzoyl indole (EAM2201 and three other analogs); Class 2, Indole–3–carboxylate/carboxamide containing naphthol/quinol (5F–PB–22 and four other analogs); and Class 3, Indazole–3–carboxamide containing valine/tert–leucine derivative (5F–AMB and five other analogs). The calculated lipophilicity index log P, the octanol/water participation coefficient, of those SCs in Classes 1, 2, and 3 ranged between 5.01–8.14, 5.80–6.74 and 2.29–3.81, respectively. Class 3 SCs were detectable in 12 out of 13 urine specimens, but those in Classes 1 and 2 were not detected in urine. Our analytical results indicated that the boundary line for their detectability in urine lies between log P 4 and 5. The blood concentrations of Class 3 SCs varied widely (0.0036–31ng/ml) depending on their log P, while much smaller variation was observed among those in Class 2 (0.10–5.0ng/ml).