Differentiating Positional Isomers of the 2-(Dimethoxyphenyl)-N-(2-(trifluoromethoxy)benzyl)ethanamine Series: A Chromatography-Mass Spectrometry Approach.

Abstract

Synthetic derivatives of phenylethanamine, specifically 2-(2,5-dimethoxyphenyl)-N-((2-substituted)benzyl)ethanamines, regularly appear on the global market of new designer drugs and have been reported to be associated with adverse effects in humans who consume them. At the same time, their positional isomers may lack psychoactive effects. These compounds are not currently regulated by legislation and could potentially be used for medical purposes in the future. Continuing the study of the properties of 2-(2,5-dimethoxyphenyl)-N-((2-substituted)benzyl)ethanamines with different substituents, a poorly studied series of 2-(dimethoxyphenyl)-N-(2-(trifluoromethoxy)benzyl)ethanamines (NBOMe(F)) with a trifluoromethoxy group (OCF₃) in the ortho-position of the N-benzyl fragment is of interest. Gas chromatographic analysis revealed the existence of a critical pair of isomers when using an HP-5 type column, the differentiation of which is difficult under varying temperature conditions of the column thermostat. Their separation was achieved on a DB-17MS column under isothermal conditions at a temperature of 210°C. A method using thin-layer chromatography for the differentiation of this critical pair of isomers is also proposed. Retention indices of the isomeric compounds of the NBOMe(F) series and their N-trifluoroacetyl derivatives have been determined, which can serve as an additional identification criterion for gas chromatographic analysis. It has been shown that differentiation of NBOMe(F) isomers using electron ionization mass spectra is only possible if the spectra of both the isomers themselves and their N-trifluoroacetyl derivatives, which exhibit significant differences, are recorded. As an alternative method for differentiating the isomeric compounds, an approach using high-performance liquid chromatography-tandem mass spectrometry, which does not require derivatization, is proposed.