This Is AuburnElectronic Theses and Dissertations

Mass Spectral and Chromatographic Studies on a Series Of Regioisomers and Isobaric Derivatives Related to Methylenedioxymethamphetamines




Awad, Tamer

Type of Degree



Pharmacal Sciences


The popular drug of abuse 3,4-methylenedioxymethamphetamine (MDMA) has regioisomeric and isobaric substances of mass equivalence, which have similar analytical properties and thus the potential for misidentification. Direct regioisomers of MDMA include ring and side chain methylenedioxy substitution patterns and the indirect regioisomers include methoxymethcathinones. The methoxy methyl ring substituted methamphetamines constitute the major category of isobaric substances evaluated in this study. The direct and indirect regioisomers of MDMA and also isobaric substances related to MDMA were synthesized and compared to MDMA by using gas chromatographic and spectrometric techniques. The spectrometric studies of the direct regioisomers and isobaric substances of MDMA indicated that they can not be easily differentiated by mass spectrometry or ultraviolet (UV) spectrophotometry. The synthesized compounds were converted to their perfluoroacyl derivatives, pentafluropropyl amides (PFPA) and heptaflurobutryl amides (HFBA), in an effort to individualize their mass spectra and to improve chromatographic resolution. Derivatized MDMA was easily distingushed from its derivatized direct and indirect regioisomers using mass spectrometry. Unique fragment ions were observed for the various direct regioisomeric side chains and the methoxymethcathinones. However, it was hard to characterize perfluroacyl derivatives of MDMA from most of the derivatized methoxy methyl ring substituted methamphetamines (isobaric substances) of the same side chain substitution pattern. Gas chromatographic studies indicated that the optimum separation of direct and indirect regioisomers of MDMA was obtained when a 100% dimethyl polysiloxane column was used at gradient temperature program rates. Isobaric substances related to MDMA were divided into subset groups based on the methoxy group position on the aromatic ring and were found to have different elution properties than MDMA and therefore misidentification due to co-elution can be eliminated using 100% dimethyl polysiloxane and trifluoropropyl methyl polysiloxane columns. The mass spectral and chromatographic properties of methoxy methyl ring substituted phenyl acetone, as key intermediates in synthesizing methoxymethyl methamphetamines, were also evaluated and the ten ketones were separated from each other as well as from methylenedioxy-2- propanone on a permethylated beta cyclodextrin column using gradient temperature program rates.