Thermal Degradation of Synthetic Cathinones: Implications for Forensic Toxicology

Abstract

The synthetic cathinones represent an important class of designer drugs. The widespread attention and publicity associated with these psychostimulants have resulted in numerous legislative actions at state and federal levels throughout the USA. These amphetamine-like compounds are characterized by a β-keto functional group. Although the synthetic cathinones share many properties of their phenethylamine counterparts, the presence of the ketone moiety is responsible for a number of unique and distinct differences in terms of their chemical characteristics and properties. Thermal degradation of methcathinone was first reported several decades ago but has received limited attention. In this study, we identified in situ thermal degradation products for 18 cathinones during gas chromatography-mass spectrometry (GC-MS) analysis. Oxidative degradation arises from the loss of two hydrogens, yielding a characteristic 2 Da mass shift. Degradation products were characterized by prominent iminium base peaks with mass-to-charge ratios 2 Da lower than the parent drug, and in the case of the pyrrolidine-containing cathinones, prominent molecular ions arising from the 2,3-enamine. Chromatographic and mass spectroscopic data are described for 4-ethylmethcathinone, 4-methylethcathinone, buphedrone, butylone, ethcathinone, ethylone, flephedrone, 3,4-methylenedioxy-α-pyrrolidinobutiophenone, 3,4-methylenedioxypyrovalerone, mephedrone, methcathinone, methedrone, methylone, 4-methyl-α-pyrrolidinobutiophenone, naphyrone, pentedrone, pentylone and pyrovalerone. Degradation was minimized by lowering injection temperatures, residence time in the inlet and eliminating active sites during chromatographic analysis. Chromatographic and mass spectral data for the cathinone degradation products are presented and discussed within the context of forensic toxicological analysis, selection of appropriate instrumental methods and implications for the interpretation of results.

Multi‐class analysis of new psychoactive substances and metabolites in hair by pressurized liquid extraction coupled to HPLC‐HRMS

“…The data reported in Figure a indicated that the analytes were quite stable at the temperature tested, except for some cathinones, particularly 2‐FMC and 2‐methoxymethcathinone that gave lower recoveries particularly at 150 °C. The thermolability of cathinones has been previously reported in GC experiments and was reported to be related to the oxidative decomposition of these compounds, resulting in an enamine or imine formation . Interestingly, Archer et al studied the stability of fluoromethcathinone isomers and observed a decrease in stability for the series 4‐fluoro, 3‐fluoro and 2‐fluoromethcathinone, demonstrating that the position of the fluorine atom was of paramount importance .…”

Synthetic cathinones and stereochemistry: S enantiomer of mephedrone reduces anxiety- and depressant-like effects in cocaine- or MDPV-abstinent rats

“…Psychostimulants of the designer cathinone class (i.e., beta-ketone amphetamines) are known colloquially as “bath salts” [Karch et al, 2015; Kerrigan et al, 2016]. Mechanistically, synthetic cathinones have been classified according to two distinct actions on the monoamine system.…”

Detection of legal highs in the urine of methadone‐treated patient by LC‐MS

“…Although there are some tricks to reduce this problem, LC‐MS is a valuable alternative and is frequently used for the analysis of NPS. One example could be quantification, from only 100 µL human urine samples, of 40 NPS and their metabolites by LC‐ESI‐MS with a solid phase extraction . Other examples are evaluation of the patterns of drug abuse from London nightclubs confirming intake of psychoactive drugs within studied group or analysis of synthetic cathinones in the seized products utilizing triple quadrupole analyser .…”

“…One example could be quantification, from only 100 µL human urine samples, of 40 NPS and their metabolites by LC-ESI-MS with a solid phase extraction. 7 Other examples are evaluation of the patterns of drug abuse from London nightclubs confirming intake of psychoactive drugs within studied group 8 or analysis of synthetic cathinones in the seized products utilizing triple quadrupole analyser. 9 Apart from GC-MS and LC-MS, also capillary electrophoresis (CE) is sometimes used to confirm the presence of psychoactive substances.…”