Differentiation of ring-substituted bromoamphetamine analogs by gas chromatography-tandem mass spectrometry

Abstract

There has been a rapid increase over the last decade in the appearance of new non-controlled psychoactive substances. Minor changes in the chemical structures of these compounds, such as the extension of an alkyl residue or replacement of a single substituent, are regularly made to avoid regulatory control, leading to the manufacture of many new potentially dangerous drugs. Bromoamphetamine analogs (bromoamphetamine [Br-AP] and bromomethamphetamine (Br-MA]) are ring-substituted amphetamines that can behave as stimulants, as well as exhibiting inhibitory activity towards monoamine oxidases in the same way as amphetamines. Gas chromatography-tandem mass spectrometry (GC-MS-MS) was used in this study to differentiate ring-substituted bromoamphetamine analogs. Free bases, trifluoroacetyl derivatives, and trimethylsilyl (TMS) derivatives of six analytes were successfully separated using DB-1ms and DB-5ms columns. Electron ionization MS-MS analysis of the TMS derivatives allowed for the differentiation of three regioisomers. TMS derivatives of 2-positional isomers provided significant product ions. The spectral patterns of 3- and 4-positional isomers were different. Chemical ionization MS-MS analysis of free bases for [M+H-HBr]⁺ ions at m/z 134 and 148 allowed for differentiation of the regioisomers. The spectra of 2-positional isomers contained characteristic product ions formed by dehydrogenation at m/z 132 and m/z 146 for 2Br-AP and 2Br-MA, respectively. The spectra of 3-positional isomers contained α-cleaved iminium cations as the base peaks. The spectra of 4-positional isomers showed a tropylium cation at m/z 91 as the base peak. These results demonstrate that GC-MS-MS can be used for the differentiation of regioisomeric Br-AP analogs in forensic practice.

Keywords: Bromoamphetamine analogs; Chemical ionization; Electron ionization; GC–MS-MS; Regioisomeric differentiation.

Fig. 1

Chemical structures of regioisomers of bromoamphetamine analogs

Fig. 2

Synthesis of regioisomers of bromoamphetamine analogs

Fig. 3

Total ion current chromatograms for free bases, trifluoroacetyl (TFA) derivatives, and trimethylsilyl (TMS) derivatives of bromoamphetamine analogs. The compound names are the same as those in Fig. 1

Fig. 4

Electron ionization (EI) mass spectra for free bases of bromoamphetamine analogs. Monoisotopic mass: 213 for Br-APs, 227 for Br-MAs

Fig. 5

Product ion spectra for TMS derivatives of bromoamphetamines (Br-Aps) (precursor ions at m/z 270 [M–CH₃]⁺) and bromomethamphetamines (Br-MAs) (precursor ions at m/z 284 [M–CH₃]⁺) under EI-tandem mass spectrometry (MS). Monoisotopic mass: 285 for Br-APs-TMS, 299 for Br-MAs-TMS

Fig. 6

Chemical ionization (CI) mass spectra for free bases of bromoamphetamine analogs

Fig. 7

Product ion spectra for free bases of Br-APs (precursor ions at m/z 134 [M+H–HBr]⁺) and Br-MAs (precursor ions at m/z 148 [M+H–HBr]⁺) under CI tandem MS

Fig. 8

Product ion spectra for TMS derivatives of Br-APs (precursor ions at m/z 270 [M–CH₃]⁺) and Br-MAs (precursor ions at m/z 284 [M–CH₃]⁺) under CI tandem MS