Acute intoxication caused by synthetic cannabinoids 5F-ADB and MMB-2201: A case series

Barceló, Bernardino; Pichini, Simona; López-Corominas, Victoria; Gomila, Isabel; Yates, Chris; Busardò, Francesco Paolo; Pellegrini, Manuela

doi:10.1016/j.forsciint.2017.01.020

Cited by 86 publications

(46 citation statements)

References 11 publications

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“…Since M20 and M8 were detected in all urine samples, should be proposed as sensitive biomarkers for the consumption of 5F‐ADB. M20 was reported in three cases involving 5F‐ADB . M8 was reported by Kusano et al The biomarkers are in accordance with the biomarkers used in currently available literature.…”

Section: Discussionsupporting

confidence: 81%

“…Until now, cases involving 5F‐ADB have been reported after the first identification and quantification of 5F‐ADB in postmortem human specimens was reported in 2014 by Hasegawa et al Some metabolites of 5F‐ADB were reported in these studies. Barcelo et al reported two phase I metabolites of 5F‐ADB in urine samples taken from five patients . Kusano et al detected three metabolites of 5F‐ADB in a postmortem urine sample .…”

Section: Introductionmentioning

confidence: 99%

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Metabolic profiling of synthetic cannabinoid 5F‐ADB by human liver microsome incubations and urine samples using high‐resolution mass spectrometry

Yeter

Öztürk

2019

Drug Testing and Analysis

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5F‐ADB (methyl 2‐{[1‐(5‐fluoropentyl)‐1H‐indazole‐3‐carbonyl] amino}‐3,3‐dimethylbutanoate) is a frequently abused new synthetic cannabinoid that has been sold since at least the end of 2014 on the drug market and has been classified as an illicit drug in most European countries, as well as Turkey, Japan, and the United States. In this study, the in vitro metabolism of 5F‐ADB was investigated by using pooled human liver microsomes (HLMs) assay and liquid chromatography‐high‐resolution mass spectrometry (LC–HRMS). 5F‐ADB (5 μmol/L) was incubated with HLMs for up to 3 hours, and the metabolites were identified using LC–HRMS and software‐assisted data mining. The in vivo metabolism was investigated by the analysis of 30 authentic urine samples and was compared to the data received from the in vitro metabolism study. Less than 3.3% of the 5F‐ADB parent compound remained after 1 hour of incubation, and no parent drug was detected after 3 hours. We identified 20 metabolites formed via ester hydrolysis, N‐dealkylation, oxidative defluorination, hydroxylation, dehydrogenation, further oxidation to N‐pentanoic acid and glucuronidation or a combination of these reactions in vitro. In 12 urine samples (n = 30), 5F‐ADB was detected as the parent drug. Three of the identified main metabolites 5F‐ADB carboxylic acid (M20), monohydroxypentyl‐5F‐ADB (M17), and carboxypentyl ADB carboxylic acid (M8) were suggested as suitable urinary markers. The screening of 8235 authentic urine samples for identified 5F‐ADB metabolites in vitro resulted in 3135 cases of confirmed 5F‐ADB consumption (38%).

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Metabolic profiling of synthetic cannabinoid 5F‐ADB by human liver microsome incubations and urine samples using high‐resolution mass spectrometry

Yeter

Öztürk

2019

Drug Testing and Analysis

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“…However, other mechanisms, such as an immediate ring formation via some sort of “transesterification” (eg, the ester oxygen attacks the protonated nitrogen and methane is released to form the suggested structure), are possible. This characteristic FI at m/z 251.1184 was not described in previous 5F‐ADB publications, but different mass spectrometric systems were used, which might explain this finding.…”

Section: Resultsmentioning

confidence: 64%

Metabolic fate of the new synthetic cannabinoid 7’N‐5F‐ADB in rat, human, and pooled human S9 studied by means of hyphenated high‐resolution mass spectrometry

Richter

Maurer

Meyer

2018

Drug Testing and Analysis

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New psychoactive substances (NPS) are an important issue in clinical/forensic toxicology. 7'N-5F-ADB, a synthetic cannabinoid derived from 5F-ADB, appeared recently on the market. Up to now, no data about its mass spectral fragmentation pattern, metabolism, and thus suitable targets for toxicological urine screenings have been available. Therefore, the aim of this study was to elucidate the metabolic fate of 7'N-5F-ADB in rat, human, and pooled human S9 (pS9). The main human urinary excretion products, which can be used as targets for toxicological screening procedures, were identified by Orbitrap (OT)-based liquid chromatography-high resolution-tandem mass spectrometry (LC-HRMS/MS). In addition, possible differentiation of 7'N-5F-ADB and 5F-ADB via LC-HRMS/MS was studied. Using the in vivo and in vitro models for metabolism studies, 36 metabolites were tentatively identified. 7'N-5F-ABD was extensively metabolized in rat and human with minor species differences observed. The unchanged parent compound could be found in human urine but metabolites were far more abundant. The most abundant ones were the hydrolyzed ester (M5), the hydrolyzed ester in combination with hydroxylation of the tertiary butyl part (M11), and the hydrolyzed ester in addition to glucuronidation (M30). Besides the parent compound, these metabolites should be used as targets for urine-based toxicological screening procedures. Two urine-paired human plasma samples contained mainly the parent compound (c = 205 μg/L, 157 μg/L) and, at a higher abundance, the compound after ester hydrolysis (M5). In pS9 incubations, the parent compound, M5, and M30 were detectable among others. Furthermore, a differentiation of both compounds was possible due to different retention times and fragmentation patterns.

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“…Common methods of use include smoking and vaping [10]. In laboratory-confirmed cases of use, symptoms associated with 5F-ADB include confusion, agitation, psychosis, altered consciousness, headache, dizziness, mydriasis, and vomiting [10,11]. On the basis of multiple analytically confirmed fatalities, 5F-ADB is regarded as one of the most dangerous synthetic cannabinoids [12].…”

Section: Discussionmentioning

confidence: 99%

Impaired Driving Associated with the Synthetic Cannabinoid 5F-ADB

McCain

Jones²,

Chilbert

et al. 2018

Journal of Forensic Science & Criminology

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Synthetic marijuana compounds are more potent than Δ9-tetrahydrocannabinol (Δ9-THC) and are known to produce a wide variety of clinical symptoms including cardiac toxicity, seizures, and death. Erratic driving by a 45 y/o male was witnessed in the fall of 2017 and roadside evaluation of the driver by the responding law enforcement officer concluded that the driver was intoxicated. Comprehensive analysis of the cigarettes by gas chromatography-mass spectrometry detected the synthetic cannabinoid 5-fluoro-ADB (5F-ADB or 5F-MDMB-PINACA). Validated forensic liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were used to detect the 5-fluoro ADB metabolite 7 (26.37 ng/mL) in the driver’s blood sample. No other drugs were detected. This case report is one of the first to conclusively show that designer synthetic cannabinoids, commonly referred to as “K2” and “Spice”, can significantly impair driving at relatively low concentrations.

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Acute intoxication caused by synthetic cannabinoids 5F-ADB and MMB-2201: A case series

Cited by 86 publications

References 11 publications

Metabolic profiling of synthetic cannabinoid 5F‐ADB by human liver microsome incubations and urine samples using high‐resolution mass spectrometry

Metabolic profiling of synthetic cannabinoid 5F‐ADB by human liver microsome incubations and urine samples using high‐resolution mass spectrometry

Metabolic fate of the new synthetic cannabinoid 7’N‐5F‐ADB in rat, human, and pooled human S9 studied by means of hyphenated high‐resolution mass spectrometry

Impaired Driving Associated with the Synthetic Cannabinoid 5F-ADB

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