Differentiation of 2- and 6-isomers of (2-dimethylaminopropyl)benzofuran by tandem mass spectrometry

Reliable identification of new psychoactive substances of 2-(2-methylaminopropyl)benzofuran and 6-(2-methylaminopropyl)benzofuran is problematic when analyzing by gas chromatography–mass spectrometry method. It found that these two isomers can be reliably differentiated by MS/MS spectra obtained by collision-induced dissociation of their protonated molecules.

6-APB are serotonin receptor agonists and their pharmacological effects are similar to amphetamine-type stimulants [3,4]. In the territory of the Russia the circulation of 5-APB, 6-APB and these N-methyl derivatives is controlled by legislation.
Since mass spectra of electron ionization (EI) of isomeric compounds of 2-aminopropylbenzofuran have very significant similarity, the question of differentiation of these compounds is the important practical problem associated with the reliable identification of the compounds and their metabolites. When conducting analysis by gas chromatography-mass spectrometry using typical gas chromatography columns for drug identification with dimethylpolysiloxane nonpolar stationary phase (such as HP-5) the differentiation of compounds 5-APB and 6-APB or 5-MAPB and 6-MAPB is possible due to the differences in the values of parameters of the chromatographic retention of these compounds (Fig. 2) or their acyl derivatives [3,4].
Compound 2-MAPB ( Fig. 3) has not only very similar to the 6-MAPB EI mass spectrum (Match factor more than 900) but the same chromatographic retention parameters (retention index of the  [5] compounds GI=1546) [5], which does not allow to distinguish reliably between these compounds. The same values of retention indices were registered by us [5] for methyl (GI=1611) and trifluoroacetyl (GI=1749) derivatives of 2-MAPB and 6-MAPB.
To address the question about the possibility of accurate differentiation of 2-MAPB and 6-MAPB using mass spectrometry we have considered different method of mass spectrometric ionization of compounds. As this method the ionization by electrospray was chosen, which is increasingly used in the determination of drugs and their metabolites. Registered in terms of collision-induced dissociation (CID), high resolution MS/MS spectra of protonated molecules of compounds 2-MAPB and 6-MAPB (Fig. 4) and their methyl derivatives had significant differences that allow to identify these compounds easily.
Thus Thus, additional check CID spectra of protonated molecules of compounds 2-MAPB and 6-MAPB allow to differentiate these isomers reliably.