Our research in forensic drug chemistry involves studies to improve the differentiation of regioisomeric and isobaric compounds related to controlled drug substances. The experiments are designed to test and challenge the specificity of methods used in forensic drug sample evaluation and identification. The methylenedioxyphenethylamine group of compounds has been the focus of a significant amount of designer drug attention in recent years. Designer drugs have been described as molecular modifications of controlled substances to produce a drug species which exists just outside the scope of the current drug laws. Some countries have dealt with the legal issues surrounding these clandestine synthesized designer drugs by placing controls on individual molecular species. Other countries such as the United States have developed a controlled substance analog law attempting to proactively control many substances before they appear as clandestine drugs. In either case the forensic chemist is left with the need to specifically identify any new substance encountered in a drug sample. Regioisomeric relationships are the result of different positions of attachment of functional groups in compounds that possess the same molecular formula (elemental composition). Isobaric substances are of the same nominal mass but different elemental compositions. Regioisomeric and isobaric substances are considered a significant challenge for the analytical techniques used to identify specific substances. This is extremely important when some of these molecules are legally controlled drugs of abuse or controlled precursor substances. Gas chromatography-mass spectrometry is the mandated method of confirming drug identity in a number of forensic and regulatory situations. While the mass spectrum is often considered a specific "fingerprint" for an individual compound, there are other substances which may produce very similar or almost identical mass spectra. Such compounds having mass spectral equivalency and similar chromatographic elution properties, perhaps co-elution represent a serious analytical challenge. When the number of mass spectral equivalent isomeric substances is relatively small, chromatographic separation and reference standard availability is sufficient for differentiation. However, the continued designer exploration of some drug categories will likely produce even greater numbers of regioisomeric and isobaric substances especially among the phenethylamines. As the number of compounds having mass spectral equivalence increases so will the challenge of specific identification via chromatographic resolution and other analytical methods. The substituted phenethylamines show major fragments in their electron ionization mass spectra from cleavage of the bond between the two carbons connecting the aromatic ring and the nitrogen atom of the amine side chain. Those regioisomeric and isobaric relationships occurring within the major mass spectral fragmentation sites not only have the same molecular weight but can also yield EI decomposition ions at equal mass, equivalent mass spectra. Our work involves molecular design, organic synthesis and analytical evaluation of regioisomeric and isobaric compounds to improve analytical specificity in forensic drug chemistry.

Selected Publications M.O.F. Khan, M.S. Levi, C.R. Clark, S.Y. Ablordeppey, S.-J. Law, N. H. Wilson and R.F. Borne, "Isoquinuclidines: A Review of Chemical and Pharmacological Properties," Studies in Natural Products Chemistry Vol. 34, Atta-ur-Rahman, ed. Elsevier, Amsterdam, The Netherlands, pgs 753-787, August 2008. Tamer Awad, Jack DeRuiter and C. Randall Clark, “GC-MS Analysis of Acylated Derivatives of a Series of Side Chain Regioisomers of 2-Methoxy-4-Methyl-Phenethylamines,” J. Chromatogr. Sci., 46, 375-380 (2008). Tarek Belal, Tamer Awad, Jack DeRuiter and C. Randall Clark, “GC-MS Studies on Acylated Derivatives of 3-Methoxy-4-methyl- and 4-Methoxy-3-methyl-phenethylamines: Regioisomers Related to 3,4-MDMA,” Forensic Science International, 178, 61-82 (2008). Tamer Awad, Jack DeRuiter and C. Randall Clark*, “GC- MS Analysis of Ring and Side Chain Regioismoers of Ethoxyphenethylamines,” J. Chromatogr. Sci., 46, 671-679 (2008).