A novel method to distinguish β-methylphenylethylamines from isomeric α-methylphenylethylamines by liquid chromatography coupled to electrospray ionization mass spectrometry

Abstract

Purpose: Various phenylethylamines have been detected lately in dietary or sports supplements. N-Methyl-2-phenylpropan-1-amine (phenpromethamine) and 2-phenylpropan-1-amine (β-methylphenylethylamine, BMPEA) are known to produce mass spectra almost identical to those produced by methamphetamine (MA) and amphetamine (AP), respectively, when analyzed by liquid chromatography/mass spectrometry (LC/MS). They may interfere with the analysis of MA and AP. The aims of the present study were to determine whether some substances other than phenpromethamine and BMPEA give mass spectra similar to those given by MA or AP and to develop an analytical method of distinguishing phenpromethamine from MA and BMPEA from AP by derivatization. Methods: Twenty isomers of MA or AP were selected to be analyzed using LC/MS. Six reagents were examined for derivatization of MA, AP, phenpromethamine, and BMPEA. Three mass spectrometers from two manufacturers were evaluated for their ability to reproduce the data. Results: All isomers except phenpromethamine and BMPEA were shown to be distinguishable from MA and AP by their mass spectra. For the discrimination of isomeric pairs, derivatization using N-succinimidyl-4-nitrophenylacetate was found to be the best for tandem mass spectrometry and that using 4-nitrobenzoyl chloride was the best for in-source collision-induced dissociation. One or more ions from each pair of isomers gave adequate difference in their relative intensities according to the World Anti-Doping Agency criteria. Conclusions: The newly developed method was proved to be usable for discriminating among those phenylethylamines.