benzofurans and ethylphenidate

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.

Topics: Benzofurans; Chromatography, High Pressure Liquid; Gas Chromatography-Mass Spectrometry; Hair; Humans; Immunoassay; Male; Methylphenidate; Psychotropic Drugs; Substance Abuse Detection; Substance-Related Disorders; Tandem Mass Spectrometry; Young Adult

The illicit drug market of psychoactive substances for human abuse is continuously expanding and developing. Besides already known substance classes like cathinones, amphetamines or synthetic cannabinoids, further derivatives such as benzofurys, thiophenes, and structural analogues of methylphenidate entered the global market recently. As many of these new compounds contain a stereogenic centre it is supposed that their isomers may differ in their pharmacological effects as it is the case with amphetamines or several chiral active pharmaceutical ingredients, for instance. In the course of this study, a method for the chiral separation of a set of 16 recreational drugs by CE was developed. The aim was to separate the analytes into their enantiomers at equal conditions within short time. Sulfobutylether β-cyclodextrin served as chiral selector in an aqueous ammonium acetate solution containing ACN. For method optimization, methedrone and ethylphenidate were used as model compounds to find the appropriate concentration of chiral selector. Moreover, the influence of the pH value on enantioseparation was tested. Fourteen or 16 mM sulfobutylether β-cyclodextrin, 50 mM ammonium acetate solution (pH 4.5) with 10% ACN were found to be optimal for enantioseparation of seven benzofurys, four cathinones, two diphenidines, ethylphenidate, methiopropamine, and thiothinone. Most of them were baseline resolved at migration times below 25 min.

Topics: Acetonitriles; Benzofurans; beta-Cyclodextrins; Electrophoresis, Capillary; Hydrogen-Ion Concentration; Illicit Drugs; Methylphenidate; Propylamines; Psychotropic Drugs; Reproducibility of Results; Stereoisomerism; Substance Abuse Detection