This Is AuburnElectronic Theses and Dissertations

Mass Spectral, Infrared and Chromatographic Studies on Designer Drugs of the Piperazine Class




Hafiz Abdel-Hay, Karim

Type of Degree



Pharmacal Sciences


The controlled drug 3,4-methylenedioxybenzylpiperazine (3,4-MDBP) has regioisomeric and isobaric substances of mass equivalence, which have similar analytical properties and thus the potential for misidentification. The direct regioisomers of 3,4-MDBP include the 2,3-methylenedioxy substitution pattern and the indirect regioisomers include the three ring substituted methoxybenzoylpiperazines. The ethoxy and methoxymethyl ring substituted benzylpiperazines constitute the major category of isobaric substances evaluated in this study. The direct and indirect regioisomers of 3,4-MDBP and also isobaric substances related to MDBP were synthesized and compared to 3,4-MDBP by using gas chromatographic and spectrophotometric techniques. The GC-MS studies of the direct regioisomers and isobaric substances of 3,4-MDBP indicated that they can not be easily differentiated by mass spectrometry. The synthesized compounds were converted to their perfluoroacyl derivatives, trifluoroacetyl (TFA), pentafluoropropionyl amides (PFPA) and heptafluorobutryl amides (HFBA), in an effort to individualize their mass spectra and to improve chromatographic resolution. Derivatized 3,4-MDBP was not distingushed from its derivatized regioisomers or isobars using mass spectrometry. No unique fragment ions were observed for the various regioisomeric and the isobaric compounds. Gas chromatographic studies indicated that the optimum separation of regioisomers and isobaric compounds of 3,4-MDBP was obtained when a 100% trifluoropropyl methyl polysiloxane column was used at gradient temperature program rates. Exact mass determination techniques such as gas chromatography coupled to time of fight mass spectrometric detection (GC-TOF-MS) was used and proved to be successful in discriminating among isobaric compounds that have the same nominal mass but are different in their elemental composition and hence their exact masses. On the other hand, GC-TOF-MS is not a successful tool to differentiate between regioisomers that have both the same nominal and exact masses. In addition, the gas chromatography coupled to infrared detection (GC-IRD) proved to be an excellent tool in differentiating 3,4-MDBP from all of its regioisomers and isobars. Other ring substituted benzylpiperazines such as chloro, methoxy and methylbenzylpiperazines were prepared and their analytical properties were studied in this dissertation. Other chemical classes of piperazines were also synthesized and evaluated during this study. Some ring substituted benzoylpiperazines, 1-(phenyl)-2-piperazinopropanes (PPPs) that have amphetamine-like side chain and 1-(phenyl)-2-piperazinopropanones which have cathinone-like side chain (PPPOs) were synthesized in the lab. Their mass spectral, infrared and gas chromatographic separation and properties were studied too. In addition to that, isotope labeling experiments such as deuterium (D) and carbon 13 (13C) labeling were used to confirm mass spectrometric fragmentation mechanisms that result in the formation of some key fragment ions or to confirm the elemental composition of these fragment ions.