Identification of 5-Fluoro ADB in Human Whole Blood in Four Death Cases

Usui, Kiyotaka; Fujita, Yuji; Kamijo, Yoshito; Kokaji, Tetsuo; Funayama, Masato

doi:10.1093/jat/bkx088

Cited by 30 publications

(23 citation statements)

References 13 publications

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“…There was no sample where only parent 5F‐ADB was detected. The low blood concentration of 5F‐ADB and AMB‐FUBINACA are consistent with reports where median concentration of related parent SCs in blood was at or below 1 ng/mL . 5F‐ADB was also detected in 70 post‐mortem blood samples at concentrations between 0.10 and 1.55 ng/mL, with a mean of 0.40 ng/mL …”

Section: Resultssupporting

confidence: 85%

Simultaneous analysis of 29 synthetic cannabinoids and metabolites, amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

Ong

Kappatos

Russell

et al. 2019

Drug Testing and Analysis

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We describe the validation of a method for the simultaneous analysis of 29 synthetic cannabinoids (SCs) and metabolites, 4 amphetamines, and 2 cannabinoids in human whole blood. This method enables one analysis to cover what previously required multiple analyses for these classic and novel drugs-of-abuse with diverse physicochemical properties. The scope of targeted analytes was based on the most prevalent drugs-ofabuse and SCs encountered at the New Zealand border in 2017 and included parent compounds and metabolites belonging to the indole and indazole carboxamide, quinolinyl indole carboxylate, and naphthoylindole classifications. Samples were prepared by supported-liquid-extraction (SLE) followed by liquid chromatography −tandem mass spectrometry (LC−MS/MS) analysis with positive electrospray ionization (ESI). The method was validated with respect to selectivity, matrix effects, process efficiency, sensitivity, repeatability, extract stability, and carryover for qualitative confirmation. Linearity as well as accuracy and precision data at target decision concentrations were also evaluated. The limits of detection and confirmation ranged from 0.1 to 6.0 ng/mL and 1.0 to 6.0 ng/mL, respectively. The described method was successfully applied to the analysis of 564 ante-and post-mortem blood samples in 2018. There were 132 cases (23%) with positive findings of at least one SC, with the five most commonly detected SCs being AMB-FUBINACA and/or acid (61%), 5F-ADB and/or acid (40%), ADB-FUBINACA (11%), 5F-MDMB-PICA acid (6%), and MDMB-FUBINACA acid (6%). The results also demonstrate the predominant presence of metabolites at higher levels than the unchanged parent SCs in blood, highlighting the need to maintain forensic screening methods capable of the simultaneous detection of both parent compounds and metabolites.

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Section: Resultssupporting

confidence: 85%

Simultaneous analysis of 29 synthetic cannabinoids and metabolites, amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

Ong

Kappatos

Russell

et al. 2019

Drug Testing and Analysis

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show abstract

“…Sample preparation and extraction procedures varied widely: liquid-liquid extraction was the most frequently used, though solid-phase extraction (24,44,47,53) and QuEChERS dispersive solid-phase extraction (29,30,35,50) were also reported. Only in a minority of the cases, the standard addition method was employed for quantification (19,23,28,30).…”

Section: Analytical Issuesmentioning

confidence: 99%

“…Atherosclerotic disease and other cardiac abnormalities, such as cardiomegaly and dilatative cardiomyopathy, pose an additional challenge to the assessment of the role of SCRAs in death cases (50,61). In fact, drugs can either exacerbate a preexisting condition, or be considered an irrelevant finding (33).…”

Section: Cause and Mechanism Of Death Tssmentioning

confidence: 99%

“…In cases of polydrug abuse, the evaluation of role cannot leave aside concentrations of xenobiotics, leading to attribution of different TSS on a case-by-case basis, e.g., TSS U with 3 g/L of ethanol, positive unquantified SCRAs and suspected arrhythmias (20) vs TSS 3 with 1.8 g/L ethanol, 1.5 ng/mL AB-CHMINACA and acute cardiorespiratory depression (50).…”

Section: Cause and Mechanism Of Death Tssmentioning

confidence: 99%

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Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists

et al. 2020

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Background: Synthetic cannabinoid receptor agonists (SCRAs) have become the largest group of new psychoactive substances monitored by the European Union Early Warning System. Despite the wide diffusion on the market, data regarding effects, toxicities, and mechanisms as well as toxic/lethal doses are still scarce. Methods: A comprehensive literature search for articles published up to January 2019 was performed in multiple electronic databases. Only cases of death in which toxicological analyses revealed the presence of SCRAs in blood or urine and at least an external examination was performed, including those occurred in emergency departments, were included. Results: Of 380 studies identified, 354 were excluded, while 8 additional manuscripts were included through the screening of relevant references cited in the selected articles. A total number of 34 manuscripts (8 case series and 26 case reports) were included. Conclusions: Typical toxic ranges for SCRAs have not been so far identified, and the results of toxicological analyses should be interpreted with caution. In death cases involving SCRAs, a thorough post-mortem examination is a prerequisite to assess the role of the substance use in the deceased and to identify a probable mechanism of death. Even after a comprehensive analysis of clinical, circumstantial, toxicological, and autoptic data, the cause and manner of death remain unclear in some cases.

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“…Importantly, hydroxypentyl metabolites detected from metabolism experiments with pooled human liver microsomes were also detected in urine samples from two individuals who had been suspected of consuming AB-PINACA , demonstrating that these metabolic products occur in humans. 5F-ADB/5F-MDMB-PINACA, which was implicated in four deaths in Japan of people who had been in possession of a product called "Heart Shock BLACK" (Usui et al, 2018) and others (Hasegawa et al, 2015;Kusano et al, 2018), can also be metabolized to form hydroxylated metabolites, including at the 5 position of the pentyl chain (Barcelo et al, 2017). Metabolism of other synthetic cannabinoids, including AMB, 5F-AMB (Andersson et al, 2016), and EG-018 (Mogler et al, 2018), have been reported to lead to hydroxypentyl metabolites.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Cannabinoid Hydroxypentyl Metabolites Retain Efficacy at Human Cannabinoid Receptors

Gamage

Farquhar

McKinnie

et al. 2018

J Pharmacol Exp Ther

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Synthetic cannabinoids (SCs) are novel psychoactive substances that are easily acquired, widely abused as a substitute for cannabis, and associated with cardiotoxicity and seizures. Although the structural bases of these compounds are scaffolds with known affinity and efficacy at the human cannabinoid type-1 receptor (hCB 1 ), upon ingestion or inhalation they can be metabolized to multiple chemical entities of unknown pharmacological activity. A large proportion of these metabolites are hydroxylated on the pentyl chain, a key substituent that determines receptor affinity and selectivity. Thus, the pharmacology of SC metabolites may be an important component in understanding the in vivo effects of SCs. We examined nine SCs (AB-PINACA, 5F-AB-PINACA, ADB/MDMB-PINACA, 5F-ADB, 5F-CUMYL-PINACA, AMB-PINACA, 5F-AMB, APINACA, and 5F-APINACA) and their hydroxypentyl (either 4-OH or 5-OH) metabolites in [ 3 H]CP55,940 receptor binding and the [ 35 S] GTPgS functional assay to determine the extent to which these metabolites retain activity at cannabinoid receptors. All of the SCs tested exhibited high affinity (,10 nM) and efficacy for hCB 1 and hCB 2 . The majority of the hydroxypentyl metabolites retained full efficacy at hCB 1 and hCB 2 , albeit with reduced affinity and potency, and exhibited greater binding selectivity for hCB 2 . These data suggest that phase I metabolites may be contributing to the in vivo pharmacology and toxicology of abused SCs. Considering this and previous reports demonstrating that metabolites retain efficacy at the hCB 1 receptor, the full pharmacokinetic profiles of the parent compounds and their metabolites need to be considered in terms of the pharmacological effects and time course associated with these drugs.

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Identification of 5-Fluoro ADB in Human Whole Blood in Four Death Cases

Cited by 30 publications

References 13 publications

Simultaneous analysis of 29 synthetic cannabinoids and metabolites, amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

Simultaneous analysis of 29 synthetic cannabinoids and metabolites, amphetamines, and cannabinoids in human whole blood by liquid chromatography–tandem mass spectrometry – A New Zealand perspective of use in 2018

Post-Mortem Toxicology: A Systematic Review of Death Cases Involving Synthetic Cannabinoid Receptor Agonists

Synthetic Cannabinoid Hydroxypentyl Metabolites Retain Efficacy at Human Cannabinoid Receptors

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