N-(2-Methoxybenzyl)-2-(trimethoxyphenyl)ethanamines (TMPEA-NBOMe series) constitute a relatively new group of synthetic compounds, some of which are known as psychotomimetics on the illicit drug market and are subject to legal control in many countries (e.g., N-(2-methoxybenzyl)-2-(3,4,5-trimethoxyphenyl)ethanamine, also known as Mescaline-NBOMe). Like their 2,5-dimethoxy analogues (25X-NBOMe series), they act as agonists at 5-HT2A receptors and affect behavioral and cognitive functions, albeit to a lesser extent. When the relative arrangement of the three methoxy groups on the phenylethyl moiety is altered (positional isomers), compounds of the TMPEA-NBOMe series may lack psychoactive effects and therefore possess a legal status. The present study explores the potential of chromatography and mass spectrometry to differentiate positional isomers of the TMPEA-NBOMe series that differ in the location of the three methoxy groups on the phenylethyl moiety and that have different legal statuses. Differentiation of positional isomers by gas chromatography was achieved through the separation of their trifluoroacetyl derivatives on an HP-5 type column under isothermal conditions (230°C). Retention indices were determined for both the underivatized TMPEA-NBOMe isomers and their N-trifluoroacetyl derivatives, providing additional criteria for identification in GC analysis. It was found that these isomers could be distinguished by electron ionization mass spectrometry only when mass spectra were recorded for both the underivatized compounds and their N-trifluoroacetyl derivatives, since the spectra of the latter exhibited substantial differences depending on the position of the three methoxy groups. As an alternative, this study proposes a derivatization-free approach using high-performance liquid chromatography-tandem mass spectrometry.
