Citation

Kusano M, Zaitsua K, Taki K, Hisatsune K, Nakajima J, Moriyasu T, Asano T, Hayashi Y, Tsuchihashi H, Ishii A. Drug Test. Anal. 2018; 10(2): 284-293.

Affiliation

Department of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, Nagoya, Japan.

Copyright

(Copyright © 2018, John Wiley and Sons)

DOI

10.1002/dta.2215

PMID

28544560

Abstract

Despite the implementation of the new blanket scheduling system in 2013, new psychoactive substance (NPS) abuse remains a serious social concern in Japan. We present a fatal intoxication case involving 5F-ADB (methyl 2-[1-(5-fluoropentyl)-1H-indazole-3-carboxamido]-3,3-dimethylbutanoate) and diphenidine. Postmortem blood screening by liquid chromatography/quadrupole time-of-flight mass spectrometry (LC/Q-TOFMS) in the information dependent acquisition (IDA) mode only detected diphenidine. Further urinary screening using an in-house database containing new NPS and metabolites detected not only diphenidine but also possible 5F-ADB metabolites; subsequent targeted screening by LC/tandem mass spectrometry (LC/MS/MS) allowed for the detection of very low level of unchanged 5F-ADB in postmortem heart blood. Quantification by standard addition resulted in the postmortem blood concentrations to be 0.19±0.04 ng/mL for 5F-ADB and 12±2.6 ng/mL for diphenidine. Investigation of the urinary metabolites revealed pathways involving ester hydrolysis (M1) and oxidative defluorination (M2), and further oxidation to the carboxylic acid (M3) for 5F-ADB. Mono- and di-hydroxylated diphenidine metabolites were also found. The present case demonstrates the importance of urinary metabolite screening for drugs with low blood concentration. Synthetic cannabinoids (SCs) fluorinated at the terminal N-alkyl position are known to show higher cannabinoid receptor affinity relative to their non-fluorinated analogues; 5F-ADB is no exception with high CB1 receptor activity and much greater potency than Δ(9) -THC and other earlier SCs, thus we suspect its acute toxicity to be high comparable to other structurally relative SC analogues. The low blood concentration of 5F-ADB may be attributed to enzymatic and/or non-enzymatic degradation, and further investigation into these possibilities is underway.

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Language: en

Keywords

5F-ADB; LC/MS/MS; LC/Q-TOFMS; designer drugs; diphenidine; metabolism; new psychoactive substances; synthetic cannabinoids