Fatal intoxication by 5F–ADB and diphenidine: Detection, quantification, and investigation of their main metabolic pathways in humans by LC/MS/MS and LC/Q‐TOFMS

• DOI: 10.1002/dta.2215
• Publication Date: 2017-05-23T22:31:25Z
• Authors: Maiko Kusano; Kei Zaitsu; Kentaro Taki; Kazuaki Hisatsune; Jun'ichi Nakajima; Takako Moriyasu; Tomomi Asano; Yumi Hayashi; Hitoshi Tsuchihashi; Akira Ishii
• Keywords: Psychotropic Drugs; Indazoles; Cannabinoids; Urinalysis; 01 natural sciences; 0104 chemical sciences; 3. Good health; Japan; Piperidines; Receptor, Cannabinoid, CB1; Tandem Mass Spectrometry; Humans; Metabolic Networks and Pathways; Chromatography, Liquid

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