TY  - JOUR
PY  - 2018//
TI  - Fatal intoxication by 5F-ABD and diphenidine: detection, quantification, and investigation of their main metabolic pathways in human by LC/MS/MS and LC/Q-TOFMS
JO  - Drug testing and analysis
A1  - Kusano, Maiko
A1  - Zaitsua, Kei
A1  - Taki, Kentaro
A1  - Hisatsune, Kazuaki
A1  - Nakajima, Jun'ichi
A1  - Moriyasu, Takako
A1  - Asano, Tomomi
A1  - Hayashi, Yumi
A1  - Tsuchihashi, Hitoshi
A1  - Ishii, Akira
SP  - 284
EP  - 293
VL  - 10
IS  - 2
N2  - 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.<br><br>This article is protected by copyright. All rights reserved.<p />  <p>Language: en</p>
LA  - en
SN  - 1942-7603
UR  - http://dx.doi.org/10.1002/dta.2215
ID  - ref1
ER  -