Synthesis, determination of analytical characteristics and differentiation of positional isomers in the series of N-(2-methoxybenzyl)-2-(dimethoxyphenyl)ethanamine by means of chromatography-mass spectrometry.

: N-(2-Methoxybenzyl)-2,5-dimethoxyphenethylamines (NBOMes) are synthetic phenethylamine derivatives emerging on the drugs of abuse market and reported to be associated with untoward effects in people using drugs. The mechanism of action involves agonism at serotonin 5-HT2A receptors affecting cognitive and behavioral processes. At the same time, certain isomers of NBOMes may not show any psychoactive effects. They are not controlled by legislation, and potentially can be tested as pharmaceutical drugs. The present study deals with differentiation between positional 25H-NBOMe isomers differing in the position of two methoxy groups in the phenylethyl moiety of the molecule by chromatography-mass spectrometry methods. Analysis of 25H-NBOMe isomers using gas chromatography-mass spectrometry showed that an isothermal mode appeared to be much more efficient in reliable separation of the mentioned isomers than the usually applied temperature-programming mode. Electron ionization mass spectra of 25H-NBOMe isomers were highly similar resulting in high probability of erroneous identification. On the contrary, mass spectra of their trifluoroacetyl or pentafluoropropanoyl derivatives notably simplify identification containing fragments with significant differences in abundance. Moreover, the proposed analysis with liquid chromatography-tandem mass spectrometry demonstrated the ability to distinguish 25H-NBOMe isomers without the need for derivatization.