Gas chromatography with infrared detection (GC-IRD) provides direct confirmatory data for the differentiation between the six regioisomeric aromatic ring substituted dimethoxybenzylpiperazines (DMBPs). These regioisomeric substances are resolved by GC and the vapour-phase infrared spectra clearly differentiate among the six dimethoxybenzyl substitution patterns. The mass spectra for these regioisomeric substances are almost identical. With only the 2,3-dimethoxy isomer showing one unique major fragment ion at m/z 136. Thus mass spectrometry does not provide for the confirmation of identity of any one of these compounds to the exclusion of the other isomers. Perfluoroacylation of the secondary amine nitrogen for each of the six regioisomers gave mass spectra showing some differences in the relative abundance of fragment ions without the appearance of any unique fragments for specific confirmation of structure. Gas chromatography coupled with time-of-flight mass spectrometric detection (GC-TOF) provided an additional means of confirmation of the elemental composition of the major fragment ions in the mass spectra of these compounds. Copyright © 2013 John Wiley & Sons, Ltd.