Fatal N-Ethylhexedrone Intoxication

Abstract

N-Ethylhexedrone [2-(ethyloamino)-1-phenylhexan-1-one; α-ethylaminohexanophenone; NEH] is one of the most recent synthetic cathinones that appeared on the illegal market in late 2015. The majority of information concerning the model of consumption of NEH and its impact on the body originates only from self-reports from grey literature websites and drug forums. There are only limited data associated with the concentrations of NEH in blood samples available in the literature. This article presents a case of fatal NEH intoxication and a method for the determination of this substance in whole blood. A 21-year-old man without any diagnosed diseases was admitted to the hospital due to disorientation, aggression and finally loss of consciousness. Hyperthermia (>41°C), tachycardia (>160 beats per minute), tachypnoe (20 breaths per minute), blood pressure (110/60 mmHg) and acute kidney failure were diagnosed. After a few hours of hospitalization, the patient died. A plastic bag with a white powder was found in his underwear. Analysis of the powder by another laboratory revealed cocaine hydrochloride; however, no cocaine or its metabolites were found in the biological material upon testing in our laboratory. Therefore, re-analysis of the powder was performed, and NEH was identified. Liquid-liquid extraction followed by LC–MS-MS analysis were used for the determination of NEH in blood. The validation parameters were as follows: calibration range 1–250 ng/mL, accuracy 106.5–109.9%, precision 3.5–6.3%, recovery 90.1–96.9%, LOD 0.07 ng/mL and LOQ 1 ng/mL. NEH was quantified in the blood at a concentration of 145 ng/mL. Additionally, amphetamine at low concentrations and THC-COOH were detected. Our study provided information on the possible lethal concentration and toxidrome that clinicians can observe for NEH-intoxicated patients and can be helpful during the preparation of toxicology analysis reports for a court of law for proper data interpretation.

Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017–2020: A Review

“…NEH was the most frequently seized cathinone in 2017 and among the top three in 2018, according to the 2019 European Drug Markets Report ( 104 ). NEH is sold via the internet and reportedly has the strongest effects when snorted, although it is also administered by rectal, intravenous (IV), oral or smoked (i.e., e-cigarette) routes ( 89 ). Desired effects typically occur following 10–250 mg doses with an onset of effects for 2–25 min, but effects depend on the route of administration and drug tolerance.…”

“…Desired effects typically occur following 10–250 mg doses with an onset of effects for 2–25 min, but effects depend on the route of administration and drug tolerance. In an NEH fatality, the subject presented with hyperthermia, dilated pupils, tachycardia and elevated blood pressure ( 89 ). During the autopsy, congestion in the lungs and swelling and congestion in the brain were noted at a femoral blood concentration of 145 ng/mL.…”

A review of synthetic cathinones emerging in recent years (2019–2022)

“…Additionally, N-ethylhexedrone has neurotoxic properties and is toxic to microglia [128]. There are numerous descriptions in the literature of fatal [97,127,[129][130][131][132][133] and nonfatal [100,127,[134][135][136] poisoning cases where N-ethylhexedrone has been detected in biological material (Table 1). The blood concentrations detected in fatal and non-fatal cases were in the ranges of 4-285 ng/mL and 1-84 ng/mL, respectively, and the poisoning effects described included symptoms typical of sympathomimetic and serotonergic toxidromes.…”

Finding unknown stimulants applied in food supplements using Artificial Intelligence

“…There is limited data available in the scienti c literature about the toxicity of N-ethylhexedrone in humans, but fatal N-ethylhexedrone intoxications have already been reported and recent research has shown toxicity in vitro. N-Ethylhexedrone is an internationally controlled substance since 2020 (de Mello-Sampayo, et al, 2021;Domagalska, et al, 2020;ECD, 2020;Majchrzak, et al, 2018).…”