Differentiation of regioisomeric chloroamphetamine analogs using gas chromatography–chemical ionization-tandem mass spectrometry

In recent years, a large number of clandestinely synthesized new psychoactive substances with high structural variety have been detected in forensic samples. Analytical differentiation of regioisomers is a significant issue in forensic drug analysis, because, in most cases, legal controls are placed on only one or two of the conceivable isomers. In this study, gas chromatography–tandem mass spectrometry (GC–MS–MS) was used to differentiate the regioisomers of chloroamphetamine analogs (chloroamphetamines and chloromethamphetamines) synthesized in the authors′ laboratories. Free bases, trifluoroacetyl derivatives, and trimethylsilyl derivatives were subjected to GC–MS–MS using DB-1ms, DB-5ms, and DB-17ms capillary columns, respectively. The regioisomers of chloroamphetamine analogs in all forms were well separated on the DB-5ms column. The electron ionization mass spectra of the chloroamphetamine analogs gave very little structural information for differentiation among these analogs, even after trifluoroacetyl and trimethylsilyl derivatization of the analytes. Characteristic product ions of the 2-positional isomers were observed by electron ionization-MS–MS. In contrast, chemical ionization-MS–MS of the free bases provided more structural information about chloride position on the aromatic ring when [M+H–HCl]+ was selected as a precursor ion. The results suggest that a combination of chromatographic analysis and MS–MS supports differentiation for regioisomers of chloroamphetamine analogs.