Detection of the recently emerged synthetic cannabinoid 4F‐MDMB‐BINACA in “legal high” products and human urine specimens

Abstract

Synthetic cannabinoids (SCs) remain one of the largest groups of new psychoactive substances (NPS) on the European drug market. Although the number of new derivatives occurring on the market has dropped in the last two years, newly emerging NPS still represent a challenge for laboratories performing forensic drug analysis in biological matrices. The newly emerged SC 4F‐MDMB‐BINACA has been reported by several law enforcement agencies in Europe and the USA since November 2018. This work aimed at revealing urinary markers to prove uptake of 4F‐MDMB‐BINACA and differentiate from the use of structurally similar SCs. Phase‐I metabolites detected in human urine specimens were confirmed by phase‐I metabolites generated in vitro using a pooled human liver microsomes (pHLM) assay. Seized materials and test‐purchased “legal high” products were analyzed by gas chromatography–mass spectrometry (GC–MS) and liquid chromatography−quadrupole‐time‐of‐flight−mass spectrometry (LC−qToF−MS). Human urine specimens and pHLM assay extracts were measured with liquid chromatography−electrospray ionization−tandem mass spectrometry (LC−ESI−MS/MS) and confirmed by LC−qToF−MS. In January 2019, the Institute of Legal Medicine in Erlangen (Germany) identified 4F‐MDMB‐BINACA in three herbal blends. During the same time period, the described SC was identified in a research chemical purchased online. Investigation of phase‐I metabolism led to the metabolites M10 (ester hydrolysis) and M11 (ester hydrolysis and dehydrogenation) as reliable urinary markers. Widespread distribution on the German drug market was proven by analysis of urine samples from abstinence control programs and by frequent detection of 4F‐MDMB‐BINACA in “herbal blends” and “‘research chemicals” purchased via the Internet.

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

“…In Europe, the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) notified member states of the first seizures/identifications of 4F‐MDMB‐BINACA (7) in France and the Netherlands in October 2018 and in the UK in November 2018 . It was detected in three seized herbal materials (seizure dates unknown) and one small piece of paper (seized following a positive 4F‐MDMB‐BINACA metabolite detection in a prison sample in January 2019) in Germany …”

“…35 SCRAs have been detected in herbal material, powders, e-liquids for vaping, and more recently, infused papers and other materials. [11][12][13][14][36][37][38][39][40] Between December 2014 and June 2015, the most prevalent SCRAs (and/or their metabolites) detected in both urine samples from prisoners and in drug seizures from prisons in England were 5F-AKB48 (1), (N-(adamantan-1-yl)-1-(5-fluoropentyl)-1Hindazole-3-carboxamide), also known as 5F-APINACA, and MDMB- 11 The structures of SCRA compounds discussed in this study are provided in Figure 1 and numbers in bold parentheses refer to these structures throughout the text. 12 This is similar to the ways in which blotters, also known as "tabs", containing hallucinogens, such as d-lysergic acid diethylamide (LSD) and hallucinogenic NPS, have been prepared for some time, 41 although such substances are prepared for sub-lingual use rather than smoking or vaping.…”

“…SCRAs have been detected in herbal material, powders, e‐liquids for vaping, and more recently, infused papers and other materials . Between December 2014 and June 2015, the most prevalent SCRAs (and/or their metabolites) detected in both urine samples from prisoners and in drug seizures from prisons in England were 5F‐AKB48 (1) , ( N ‐(adamantan‐1‐yl)‐1‐(5‐fluoropentyl)‐1H‐indazole‐3‐carboxamide), also known as 5F‐APINACA, and MDMB‐CHMICA (2) (methyl 2‐[[1‐(cyclohexylmethyl)indole‐3‐carboxamide]‐3,3‐ dimethylbutanoate) .…”

How to Study the Metabolism of New Psychoactive Substances for the Purpose of Toxicological Screenings—A Follow-Up Study Comparing Pooled Human Liver S9, HepaRG Cells, and Zebrafish Larvae

“…The five NPS were already shown to be extensively metabolized and therefore suitable for the current comparative metabolism study (Caspar et al, 2018b; FIGURE 1 | Chemical structures of the five new psychoactive substances included in the current study. Haschimi et al, 2019;Krotulski et al, 2019;Wagmann et al, 2019b,c). Caspar et al used pHLS9 incubations and rat urine to investigate the metabolism of 3,4-DMA-NBOMe (Caspar et al, 2018b;Wagmann et al, 2019b,c).…”

Analytical Features of Synthetic Mdmb(n)-073f Cannabimimetics and Its Markers in Biological Material

“…Как было показано ранее, из относительного содержания метаболитов в образцах мочи, основным направлением метаболизма каннабимиметика MDMB(N)-073F является гидролиз сложноэфирной связи MDMB(N)-073F с последующей конъюгацией образующегося продукта (рисунок 1). Данный метаболит фазы I биотрансформации имеет наибольшую интенсивность сигнала на хроматограммах потребителей MDMB(N)-073F и характерный массспектр, что позволяет использовать его в качестве маркера употребления этого каннабимиметика [6,7]. При этом следует учитывать, что в моче данный метаболит фазы I биотрансформации в значительной степени находится в конъюгированном виде (таблица 1), поэтому в случае применения для исследования метода ГХ-МС требуется проведение гидролиза конъюгатов.…”