β‐Methylphenylethylamines: common fragmentation pathways with amphetamines in electrospray ionization collision‐induced dissociation

Abstract

β-Methylphenylethylamines are positional isomers of amphetamines and have been discovered in sporting supplements. Although the fragmentation of the β-methylphenylethylamine and N-methyl-β-methylphenylethylamine in gas chromatography-electron ionization-mass spectrometry (GC-EI-MS) systems is significantly different to their amphetamine and methylamphetamine isomers, under electrospray ionization commonly used in liquid chromatography-mass spectrometry (LC-MS) systems, the fragmentation of each of the isomeric pairs is almost identical. The similarities in fragmentation make it possible for the misidentification of the β-methylphenylethylamines as the illicit amphetamines. It is proposed that the similarities are due to a fragmentation pathway involving a common phenonium ion intermediate. By careful control of fragmentation energies in liquid chromatography-tandem mass spectrometry (LC-MS/MS) systems and/or close examination of the relative abundances of product ions formed by collision-induced dissociation (qualifier ratios), it is possible to distinguish the β-methylphenylethylamines from the amphetamines, even if significant retention time separation is not achieved. In liquid chromatography-electrospray ionization-quadrupole time of flight (LC-ESI-QTOF) systems the mass spectra of the β-methylphenylethylamines are identical to their amphetamine isomers. In such systems, retention time separation of the isomers is critical to avoid misidentification. During this study β-methylphenylethylamine and N-methyl-β-methylphenylethylamine have been identified in commercially available sporting supplements and oral fluid samples taken during the course of road-side drugs-in-drivers and workplace testing programmes. Copyright © 2015 John Wiley & Sons, Ltd.

Differentiation of ring‐substituted regioisomers of amphetamine and methamphetamine by supercritical fluid chromatography

“…The CID spectra of AMP and MA analogues are shown in Figures 5 and 6, respectively. The expected fragmentations, speculated from the previous studies, [8][9][10][11][31][32][33] and m/z of the precursor protonated molecules and the fragment ions in the CID spectra, are summarized in Figure 7 Figure 7) was detected instead of [M + H -C 2 NH 7 ] + . Some minor characteristic peaks were observed for Br-and MeO-substituted analogues.…”

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

“…However, certain kinds of isomers are not distinguishable even with MS/MS or in-source CID. N-Methyl-2-phenylpropan-1-amine (phenpromethamine, 14) is an isomer of MA and gives a mass spectrum almost identical to that given by MA, when analyzed by liquid chromatography/mass spectrometry (LC/MS) with electrospray ionization [10,11]. Similarly, 2-phenylpropan-1-amine (β-methylphenylethylamine, BMPEA, 13), an isomer of AP, gives a mass spectrum almost identical to that given by AP [10,12].…”

“…These β-methylphenylethylamines are clearly distinguishable from α-methylphenylethylamines by gas chromatography/mass spectrometry (GC/MS) [10]. However, if LC/MS was the only technique adopted, misidentification may occur.…”

“…However, if LC/MS was the only technique adopted, misidentification may occur. Brown et al [10] reported that these four amines gave ions of different intensities in multiple reaction monitoring (MRM) after benzoylation with pentafluorobenzoyl chloride (PFB-Cl). The differences in the ratios were around 30-40%.…”

Advancing supplement science: challenges and solutions

“…In a separate investigation, Brown et al . confirmed the presence of BMPEA and its N ‐methyl derivative, the positional isomers of amphetamine and methamphetamine respectively, in a number of supplements . Avula et al .…”