Emerging Use of Isotope Ratio Mass Spectrometry as a Tool for Discrimination of 3,4-Methylenedioxymethamphetamine by Synthetic Route Hilary A. S. Buchanan, † Niamh Nic Dae ´ id,* ,† Wolfram Meier-Augenstein, ‡ Helen F. Kemp, ‡ William J. Kerr, † and Michael Middleditch † Centre for Forensic Science, Department of Pure & Applied Chemistry, University of Strathclyde, 204 George Street, Glasgow G1 1WX, Stable Isotope Forensic Facility, Environmental Engineering Research Centre, Queen’s University Belfast, David Keir Building, Belfast BT9 5AG Drug profiling, or the ability to link batches of illicit drugs to a common source or synthetic route, has long been a goal of law enforcement agencies. Research in the past decade has explored drug profiling with isotope ratio mass spectrometry (IRMS). This type of research can be limited by the use of substances seized by police, of which the provenance is unknown. Fortunately, however, some studies in recent years have been carried out on drugs synthesized in-house and therefore of known history. In this study, 18 MDMA samples were synthesized in-house from aliquots of the same precursor by three common reductive amination routes and analyzed for 13 C, 15 N, and 2 H isotope abundance using IRMS. For these three preparative methods, results indicate that 2 H isotope abundance data is necessary for discrimination by syn- thetic route. Furthermore, hierarchical cluster analysis using 2 H data on its own or combined with 13 C and/or 15 N provides a statistical means for accurate discrimina- tion by synthetic route. Drug profiling, or the ability to link batches of illicit drugs to a common source or synthetic route, has long been a goal of law enforcement agencies. Specifically, the use of synthetic drug profiles has been targeted as a law enforcement goal in the European Union Drugs Action Plan 2005-2008. 1 Analysis of drugs such as 3,4-methylenedioxymethamphetamine (MDMA or “ec- stasy”) is often performed by organic impurity profiling utilizing gas chromatography-mass spectrometry (GC-MS). 2-8 Problems with this strategy have been suggested. For instance, the clandestine laboratory may produce substances of high purity such that very few (if any) impurities remain. 9 Further, comparisons based on impurity profiling are often not sufficiently conclusive due to difficulty in achieving reproducible chromatograms as a result of low level impurities. It has also been suggested that chromatograms are often time and machine dependent, thereby confounding the comparison of results across laboratories, 9 although this type of problem may be encountered with other instrumental techniques. 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