4F‐MDMB‐BINACA: A New Synthetic Cannabinoid Widely Implicated in Forensic Casework

153

Drug misuse in prisons contributes to increased disruption and violence and negatively impacts prisoner safety, rehabilitation, and recovery. Synthetic cannabinoid receptor agonists (SCRAs), colloquially known as “spice”, are infused into papers and are of particular concern in a prison setting where they are commonly vaped. Methods for the qualitative and quantitative analysis of SCRA infused papers, including impurity profiling, were developed using gas chromatography–mass spectrometry (GC–MS) with qualitative confirmation by ultra high pressure liquid chromatography with photodiode array and quadrupole time of flight mass spectrometry detection (UPLC‐PDA‐QToF‐MS) and applied to 354 individual seized paper samples originating from 168 seizures from three Scottish prisons. Of these samples, 41% (146 samples from 101 seizures) contained at least one SCRA and multiple SCRAs were detected on 23% of these papers. Concentrations ranged from < 0.05–1.17 mg/cm2 paper, representing the first reported quantitative data for SCRA infused papers. An evolution in the SCRAs detected was demonstrated; 5F‐MDMB‐PINACA (5F‐ADB) predominated until late 2018, after which time 5F‐MDMB‐PICA and 4F‐MDMB‐BINACA became increasingly more prevalent, followed by the arrival of MDMB‐4en‐PINACA in June 2019. Concentration mapping data from two seized paper samples demonstrated that SCRA concentrations across larger papers were highly variable (0.47–2.38 mg/cm2 paper) making consistent dosing by users, and representative sampling by laboratory analysts, difficult. Near real‐time qualitative and quantitative information on SCRAs circulating in prisons acts as an early warning system for SCRAs emerging on the wider illicit market, inform the methods used to detect them and limit supply, and provide information to support harm reduction measures.

Section: Resultsmentioning

confidence: 99%

Detection and quantitation of synthetic cannabinoid receptor agonists in infused papers from prisons in a constantly evolving illicit market

Norman

Walker

McKirdy

et al. 2020

153

“…The metabolism of APP‐BINACA has not been previously reported. Theoretical metabolites of APP‐BINACA were formulated based on knowledge of previously reported metabolic pathways for similar synthetic cannabinoids . The resulting theoretical metabolites were converted to formulae (and exact mass) and added to a targeted screening program.…”

Section: Methodsmentioning

confidence: 99%

“…LC‐QTOF‐MS data independent acquisition (DIA) allowed for detection of all theoretical masses and fragment ions during the run (within 100–550 Da). This afforded the opportunity to data mine for metabolites; a process that has been used successfully in the investigation of other members of this NPS class . The above formulae for APP‐BINACA metabolites were converted to exact mass and searched in the datafiles of APP‐BINACA positive extracts using PeakView® (SCIEX, Version 2.2) and MasterView™ (SCIEX, Version 1.1).…”

Section: Methodsmentioning

confidence: 99%

“…The extract of seized drug material prepared for GC–MS analysis was diluted (1:100) in mobile phase prior to LC‐QTOF‐MS analysis. LC‐QTOF‐MS analysis was performed using a SCIEX (Framingham, MA, USA) TripleTOF® 5600+ QTOF coupled with a Shimadzu Nexera XR UHPLC . The method created separation using a standard reverse phase gradient of (A) ammonium formate (10mM, pH 3.0) and (B) 0.1% formic acid in methanol and acetonitrile (50:50, v:v) over a Phenomenex® Kinetex C18 (50 mm x 3.0 mm, 2.6 μm) analytical column.…”

Section: Methodsmentioning

confidence: 99%

“…Herein, we report identifications of APP‐BINACA in the U.S. through analysis of human biological specimens and seized drug materials using liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS), gas chromatography mass spectrometry (GC–MS), and/or nuclear magnetic resonance (NMR) spectroscopy . In addition, we examined the in vivo metabolism of APP‐BINACA through re‐interrogation of LC‐QTOF‐MS datafiles of blood cases testing positive for the parent drug and all urine cases analyzed.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Detection and characterization of the new synthetic cannabinoid APP‐BINACA in forensic casework

Krotulski

Mohr

Diamond

et al. 2019

Self Cite

New psychoactive substances (NPS) continue to emerge around the world. APP‐BINACA (or APP‐BUTINACA), a novel synthetic cannabinoid, was first reported in Europe in January 2019 and later in the United States in March 2019. APP‐BINACA was identified in the United States for the first time in blood sample extracts from forensic casework by liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS). To date, APP‐BINACA has been identified in 11 forensic toxicology cases from five states and in both medicolegal death investigations and drug impaired driving investigations. APP‐BINACA was commonly found in combination with 4F‐MDMB‐BINACA. Subsequent to its discovery in biological samples, APP‐BINACA was detected and characterized in seized drug material by gas chromatography mass spectrometry (GC–MS), LC‐QTOF‐MS, and nuclear magnetic resonance (NMR) spectroscopy. Further analysis of biological specimens resulted in the identification of five metabolites, including 4‐HO‐APP‐BINACA and APP‐BINACA 3‐phenylpropanoic acid. The frequency of APP‐BINACA detection appears to be increasing and this new synthetic cannabinoid has been identified as a possible contributory factor in adverse events, including death. This is the first literature report regarding the characterization of the new synthetic cannabinoid APP‐BINACA in humans. Since it is not widely tested for, it is not yet known the extent to which APP‐BINACA is contributing to morbidity and mortality, but forensic scientists, public health officials, and others should be aware of its possible presence and impact. Laboratories should incorporate APP‐BINACA into testing workflows for detection and confirmation, where possible.

The next generation of synthetic cannabinoids: Detection, activity, and potential toxicity of pent‐4en and but‐3en analogues including MDMB‐4en‐PINACA

Krotulski

Cannaert

Stove

et al. 2020

Self Cite

A new class of synthetic cannabinoids has emerged as new psychoactive substances (NPS). Similar in structure to JWH‐022, these substances contain alkene modifications to the tail region of the synthetic cannabinoid core structure, and nomenclature denotes these new analogues as pent‐4en or but‐3en species. Internationally, two analogues from this new series recently emerged: MDMB‐4en‐PINACA and MMB‐4en‐PICA. Previously, data regarding activity and potential toxicity were not available. In vitro assessment of cannabinoid receptor 1 (CB1) activation via the β‐arrestin 2 recruitment was studied for three (3) pent‐4en analogues, one (1) but‐3en analogue, and one (1) principal metabolite. MDMB‐4en‐PINACA (2.47 nM, 239%), MDMB‐4en‐PICA (11.5 nM, 302%), and MDMB‐3en‐BINACA (14.3 nM, 286%) were highly potent and efficacious (comparison: JWH‐018, 25.3 nM, 100%), while the potencies of MMB‐4en‐PICA and MDMB‐4en‐PINACA 3,3‐dimethylbutanoic acid were markedly lower. Modifications to core and tail structural features (i.e., indole vs. indazole) led to relatively small differences in potency, while changes among the head region led to larger differences. Sample‐mining and data‐mining conducted on toxicology samples led to the identification of MDMB‐4en‐PINACA in 25 forensic toxicology cases, including postmortem and impaired driving investigations, with case details and limited histories described herein. Moderate geographical distribution of MDMB‐4en‐PINACA was noted in the United States with emergence in the Northeast, Midwest, South, and West regions. Results from toxicology testing paired with case history show the potential for MDMB‐4en‐PINACA to cause or contribute to impairment or death. Forensic scientists, public health and public safety officials, law enforcement, clinicians, medical examiners, and coroners should consider involvement of emergent synthetic cannabinoids in their work and that new analogues containing an alkene tail can retain similar or increased potency and toxicity.