Intoxication caused by new psychostimulants: analytical methods to disclose acute and chronic use of benzofurans and ethylphenidate

Abstract

The acute and chronic toxicity of several new psychoactive substances (NPS) is unknown, and only little information is available on the pharmacology and toxicology, toxicokinetics, and detectability in body samples of such new compounds. We here propose analytical methods to disclose acute and chronic use of two types of new psychostimulants: benzofurans and ethylphenidate and we applied them to a real case of a subject attending Emergency Department with signs of acute intoxication due to psychotropic drug(s). After a urinary immunoassay screening which gave a positivity to amphetamines, general unknown gas chromatography-mass spectrometry (GC-MS) urine analysis identified 5-(2-methylaminopropyl)benzofuran (5-MAPB), 5-(2-aminopropyl)benzofuran (5-APB), 5-(2-ethylaminopropyl)benzofuran (5-EAPB), ethylphenidate, and ritalinic acid. All these substances were confirmed and quantified not only in urine but also in serum samples at different times after hospitalization by GC-MS and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). Two subsequent 2-cm hair segments were also analyzed and tested positive for the above reported substances, evidencing repeated use. The matching quantitative results in all the analyzed biological matrices demonstrated that both analytical methodologies were suitable to correctly quantify NPS involved in the current intoxication. The objective assessment of acute and chronic intoxication by the above reported compounds demonstrate that the development of analytical methods aiming at the detection of a broad spectrum of compounds in conventional and non-conventional biological matrices is helpful when facing the new challenging threat of intoxications caused by NPS.

Benzo fury: A new trend in the drug misuse scene

“…Quantitative and qualitative analysis of urine and blood or serum using either liquid or gas chromatography techniques coupled with mass spectrometry (LC‐MS and GC‐MS, respectively) were performed in the few clinical case reports publicly available. In three intoxications caused by 5‐APB, GC‐MS was successfully employed to identify and quantify the drug (Adamowicz et al, ; Barcelo et al, ; McIntyre et al, ). In the first case, LC‐MS was also applied to determine the drug‐blood concentration, but it was impossible to distinguish between the 5‐APB and 6‐APB isomers, which was only enabled by GC‐MS (Adamowicz et al, ).…”

“…In the first case, LC‐MS was also applied to determine the drug‐blood concentration, but it was impossible to distinguish between the 5‐APB and 6‐APB isomers, which was only enabled by GC‐MS (Adamowicz et al, ). In the second case report involving 5‐APB, the applicability of GC‐MS and ultrahigh‐performance LC tandem mass spectrometry (UHPLC‐MS/MS) methodologies were compared for such purposes (Barcelo et al, ). After a urinary immunoassay screening tested positive to amphetamines, 5‐APB was further confirmed and quantified by both methods in urine and serum, along with 5‐MAPB, 5‐EAPB, ethylphenidate and ritalinic acid (Barcelo et al, ).…”

“…Benzofurans, also known by users as benzo fury or benzofury , are synthetic phenethylamines and constitute the third most prominent group of new psychoactive substances (NPS) that have been introduced to the market during the current decade (United Nations Office on Drug and Crime, ). As the popularity of these novel phenethylamine derivatives increased, the number of reported intoxications, including some deaths, have been also proportionally reported in the scientific literature (Adamowicz et al, ; Adamowicz, Zuba, & Byrska, ; Barcelo et al, ; Chan, Wood, Hudson, & Dargan, ; Clemente, Chiappini, Claridge, Goodair, & Loi, ; Helander, Beck, & Backberg, ; Hofer et al, ; Jebadurai, Schifano, & Deluca, ; Kamour et al, ; Krpo, Luytkis, Haneborg, & Hoiseth, ; McIntyre, Gary, Trochta, Stolberg, & Stabley, ; Seetohul & Pounder, ; Turcant et al, ; Vallersnes et al, ). However, their toxicological profiles are far from being fully elucidated and information on the mechanisms responsible for their detrimental effects is yet to be disclosed.…”

L‐ and D‐threo ethylphenidate concentrations, pharmacokinetics, and pharmacodynamics in horses

“…In humans, EPH exposure reportedly leads to stimulation, euphoria, increased focus, and improved concentration through inhibition of dopamine and norepinephrine reuptake . In humans, there are numerous reports of intoxication following both acute and chronic ingestion . Adverse effects include chest pain, heart palpitations, agitation, and death .…”

“…In humans, there are numerous reports of intoxication following both acute and chronic ingestion . Adverse effects include chest pain, heart palpitations, agitation, and death . Although EPH exists as a racemic mixture of D‐ and L‐threo‐EPH, in vitro studies have attributed the pharmacologic effects to the D isomer .…”