Six regioisomeric methylenedioxyphenethylamines, including three known drugs of abuse (MDEA, MDMMA, MBDB) and their 2,3-methylenedioxy counterparts, have nearly identical mass spectra and cannot be distinguished by electron impact mass spectrometry alone. Differentiation requires derivatization to pentafluoropropionylamides (PFPA) or heptafluorobutrylamides (HFBA). Underivatized amines are not resolved on non-polar stationary phases but are separated on a more polar trifluoropropylmethyl polysiloxane (Rtx-200) or a permethylated beta-cyclodextran (Rtx-bDEX) column. The PFPA and HFBA derivatives of the 2,3-methylenedioxyphenethylamines elute before the corresponding 3,4-methylenedioxyphenethylamine derivatives on the Rtx-200 column.
Twelve secondary amines structurally similar to NBOMe drugs were synthesized and analyzed using gas chromatography–mass spectrometry and vapor-phase infrared spectroscopy. These compounds contain a methylenedioxy group fused to the aromatic ring of the phenethyl moiety. One subseries are N-methoxybenzyl analogues of MDA; another subseries have bromine and two methoxy groups on the benzyl side. The compounds are not known drugs of abuse, and the study provides data to distinguish them from current NBOMe drugs. The elution order on a specific GC phase was determined for regioisomers, and characteristic fragmentation patterns in mass spectra and infrared spectra confirmed substitution positions.
Nine regioisomeric compounds, derivatives of 25B-NBOMe with reversed aromatic ring substitution, were synthesized and analyzed. Their electron ionization mass spectra showed two major bromine-containing ions at m/z 229/231 and 258/260, and two non-brominated fragments at m/z 91 and 121. The relative abundance of m/z 91 was higher for 2-methoxyphenethylamine isomers, while m/z 121 was higher for the 4-methoxy isomer. Gas chromatography separated the isomers by methoxy position, with 2-methoxy eluting first and 4-methoxy last. Trifluoroacetamide derivatives of 2-bromo-4,5-dimethoxybenzyl isomers produced unique fragment ions from bromine displacement, confirmed with model compounds.
Gas chromatography with vapor phase infrared spectroscopy can distinguish the common NBOMe drugs 25I-NBOMe and 25B-NBOMe from their 3- and 4-methoxybenzyl isomers, even though their mass spectra are nearly identical and only reveal the halogen. Specific infrared absorption bands indicate the position of the methoxy group on the benzyl ring: a band at 1608 cm⁻¹ is unique to the 4-methoxy isomer, while the 2-methoxy isomer shows a band at 1593 cm⁻¹ and the 3-methoxy isomer at 1597/1598 cm⁻¹. Asymmetric aryl-O stretching frequencies also shift with substitution position. The overall shape and relative intensities of multiple bands allow clear identification of each isomer in both drug series.