{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:42:36Z","timestamp":1790754156642,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2017,7,19]],"date-time":"2017-07-19T00:00:00Z","timestamp":1500422400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:p>Despite the implementation of a 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\u2013ADB (methyl 2\u2010[1\u2010(5\u2010fluoropentyl)\u20101<jats:italic>H<\/jats:italic>\u2013indazole\u20103\u2010carboxamido]\u20103,3\u2010dimethylbutanoate) and diphenidine. Postmortem blood screening by liquid chromatography\/quadrupole time\u2010of\u2010flight mass spectrometry (LC\/Q\u2010TOFMS) in the information\u2010dependent acquisition mode only detected diphenidine. Further urinary screening using an in\u2010house database containing NPS and metabolites detected not only diphenidine but also possible 5F\u2013ADB metabolites; subsequent targeted screening by LC\/tandem mass spectrometry (LC\/MS\/MS) allowed for the detection of a very low level of unchanged 5F\u2013ADB in postmortem heart blood. Quantification by standard addition resulted in the postmortem blood concentrations being 0.19\u00a0\u00b1\u00a00.04\u00a0ng\/mL for 5F\u2013ADB and 12\u00a0\u00b1\u00a02.6\u00a0ng\/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\u2013ADB. Mono\u2010 and di\u2010hydroxylated 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 <jats:italic>N<\/jats:italic>\u2010alkyl position are known to show higher cannabinoid receptor affinity relative to their non\u2010fluorinated analogues; 5F\u2013ADB is no exception with high CB<jats:sub>1<\/jats:sub> receptor activity and much greater potency than \u0394<jats:sup>9<\/jats:sup>\u2010THC and other earlier SCs, thus we suspect its acute toxicity to be high compared to other structurally related SC analogues. The low blood concentration of 5F\u2013ADB may be attributed to enzymatic and\/or non\u2010enzymatic degradation, and further investigation into these possibilities is underway.<\/jats:p>","DOI":"10.1002\/dta.2215","type":"journal-article","created":{"date-parts":[[2017,5,23]],"date-time":"2017-05-23T18:31:25Z","timestamp":1495564285000},"page":"284-293","source":"Crossref","is-referenced-by-count":66,"title":["Fatal intoxication by 5F\u2013ADB and diphenidine: Detection, quantification, and investigation of their main metabolic pathways in humans by LC\/MS\/MS and LC\/Q\u2010TOFMS"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1892-372X","authenticated-orcid":false,"given":"Maiko","family":"Kusano","sequence":"first","affiliation":[{"name":"Department of Legal Medicine and Bioethics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kei","family":"Zaitsu","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine and Bioethics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Taki","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine and Bioethics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Hisatsune","sequence":"additional","affiliation":[{"name":"Forensic Science Laboratory Aichi Prefectural Police Headquarters  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun'ichi","family":"Nakajima","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute of Public Health  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takako","family":"Moriyasu","sequence":"additional","affiliation":[{"name":"Tokyo Metropolitan Institute of Public Health  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine and Bioethics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumi","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Radiological and Medical Laboratory Sciences Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Tsuchihashi","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine and Bioethics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine and Bioethics Nagoya University Graduate School of Medicine  Nagoya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,7,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.1584"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.1483"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/SAR.S73586"},{"key":"e_1_2_7_5_1","first-page":"37","article-title":"Emerging drugs of abuse: Current perspectives on substituted cathinones","volume":"5","author":"Paillet\u2010Loilier M","year":"2014","journal-title":"Subst. 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