Role of five synthetic reaction conditions on the stable isotopic composition of 3,4-methylenedioxymethamphetamine.

The identification of links between seizures of illicit 3,4-methylenedioxymethamphetamine (MDMA or "ecstasy") has been a global target of law enforcement agencies in recent years. Previous work has shown that, when the reaction conditions are carefully repeated from batch to batch, stable isotope ratios allow the discrimination of MDMA.HCl batches according to synthetic route used for manufacture. In this study, the effects of altering five reaction conditions relating to the Pt/H(2) reductive amination synthesis were, for the first time, systematically investigated using a two level, five factor factorial design. Results indicate that the delta(2)H values of MDMA.HCl are affected by the length of imine stir time, and the delta(15)N values are affected by the degree of excess methylamine employed. Furthermore, the delta(13)C and delta(18)O values have been shown to be affected by the efficiency of the reaction, despite the similarity in carbon and oxygen composition of the starting material and product molecules. In addition to being of theoretical importance in this field of analytical science overall, this work is essential in order to more fully contextualize the interpretation of IRMS data which may be used as potential forensic evidence.

Characterization of route specific impurities found in methamphetamine synthesized by the Leuckart and reductive amination methods.

Impurity profiling of seized methamphetamine can provide very useful information in criminal investigations and, specifically, on drug trafficking routes, sources of supply, and relationships between seizures. Particularly important is the identification of "route specific" impurities or those which indicate the synthetic method used for manufacture in illicit laboratories. Previous researchers have suggested impurities which are characteristic of the Leuckart and reductive amination (Al/Hg) methods of preparation. However, to date and importantly, these two synthetic methods have not been compared in a single study utilizing methamphetamine hydrochloride synthesized in-house and, therefore, of known synthetic origin. Using the same starting material, 1-phenyl-2-propanone (P2P), 40 batches of methamphetamine hydrochloride were synthesized by the Leuckart and reductive amination methods (20 batches per method). Both basic and acidic impurities were extracted separately and analyzed by GC/MS. From this controlled study, two route specific impurities for the Leuckart method and one route specific impurity for the reductive amination method are reported. The intra- and inter-batch variation of these route specific impurities was assessed. Also, the variation of the "target impurities" recently recommended for methamphetamine profiling is discussed in relation to their variation within and between production batches synthesized using the Leuckart and reductive amination routes.

Emerging use of isotope ratio mass spectrometry as a tool for discrimination of 3,4-methylenedioxymethamphetamine 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. 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 13C, 15N, and 2H isotope abundance using IRMS. For these three preparative methods, results indicate that 2H isotope abundance data is necessary for discrimination by synthetic route. Furthermore, hierarchical cluster analysis using 2H data on its own or combined with 13C and/or 15N provides a statistical means for accurate discrimination by synthetic route.