Eutylone Intoxications—An Emerging Synthetic Stimulant in Forensic Investigations

Abstract

Synthetic stimulants are the largest class of novel psychoactive substances (NPS) identified each year by forensic laboratories internationally. While hundreds of these drugs appear in drug powders, only a few proliferate in use among forensically relevant populations, eventually emerging in postmortem and clinical investigations. Beta-keto-methylenedioxyamphetamines (i.e., NPS with names ending in “ylone”) are currently the most popular subclass of synthetic stimulants. Leading up to its federal scheduling in 2018, N-ethyl pentylone was the most encountered synthetic stimulant. The popularity of N-ethyl pentylone declined once it was scheduled but it was quickly replaced by eutylone (bk-EBDB), a structurally related analogue from the same family. In cases encountered between January 2019 and April 2020, eutylone was quantitatively confirmed in 83 forensic investigations, including postmortem cases and driving under the influence of drugs (DUID) cases. Matrix types included blood, urine, and tissue. Eutylone was identified in cases submitted from thirteen states, demonstrating proliferation around the United States; Florida accounted for 60% of the positive cases. The mean concentration of eutylone in postmortem blood was 1,020 ng/mL (standard deviation = ±2,242 ng/mL; median = 110 ng/mL, range = 1.2-11,000 ng/mL, n = 67). The mean concentration of eutylone in blood from DUID cases was 942 ng/mL (standard deviation = ±1,407 ng/mL; median = 140 ng/mL, range = 17-3,600 ng/mL, n = 7). This report includes cause and manner of death data for 22 postmortem cases. Further analysis of authentic human specimens revealed the presence of three eutylone metabolites, including one unique biomarker and one metabolite in common with butylone. Laboratories should be aware that eutylone may be present in cases of suspected Ecstasy, “Molly”, and/or MDMA use, causing or contributing to impairment or death.

Eutylone and Its Structural Isomers Interact with Monoamine Transporters and Induce Locomotor Stimulation

“…Since that time, it has been detected in 17 countries across Europe, but it was only during 2019–2020 that there has been a marked increase in the availability of eutylone in the European Union, the U.S., New Zealand, and other parts of the world . In the U.S., eutylone was the most commonly reported cathinone in drug seizures and biological samples during 2019, a trend that has continued through 2020. − These data demonstrate that the availability and misuse of eutylone are increasing worldwide.…”

“…Recently, 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)­butan-1-one, also known as “bk-EBDB” or “eutylone”, has emerged on recreational drug markets in the United States (U.S.) and elsewhere . From a chemical structure perspective, eutylone is a methylone analog that contains ethyl groups at both the α-carbon and amine positions (see Figure ).…”

Quantitative determination and metabolic profiling of synthetic cathinone eutylone in vitro and in urine samples by liquid chromatography tandem quadrupole time‐of‐flight mass spectrometry

“…and 1.2-11,000 ng/ml in blood samples of post-mortem cases. 23 Krotulski et al also found evidence of use of multiple drugs besides eutylone, like cocaine, fentanyl and methamphetamine. 23 The metabolites detected in authentic samples are also shown in Although phase II metabolites are not included in this report, the concentrations of 4-hydroxy-3-methoxy and 3-hydroxy-4-methoxy metabolites could be assumed to increase after glucuronidase and sulfatase hydrolysis, based on some published studies.…”

Determination of new psychoactive substances and other drugs in postmortem blood and urine by UHPLC–MS/MS: method validation and analysis of forensic samples

“…N-Ethylpentylone concentrations in postmortem blood ranged from 7 to 170 ng/mL in Brazilian cases [6] and from 12 to 1200 ng/mL in USA [35,36]. Lee et al [32] reported seven postmortem cases with ethylone detected in blood, ranging from 38 to 2572 ng/mL and Krotulski et al [37] reported 22 postmortem cases involving eutylone, with blood levels ranging from 1.2 to 11,000 ng/mL and two urine samples (60 and > 10,000 ng/mL). To the best of our knowledge, this is the first study that uses a QuEChERS method for the analysis of a large number of analytes that included 25R-NBOMe and 25R-NBOH family compounds in blood and urine.…”