An investigation into the ability of three analytical techniques to discriminate batches of methlamphetamine prepared by seven synthetic routes

This project evaluates the abilities of gas chromatography mass spectrometry (GCMS), isotope radio mass spectrometry (IRMS) and inductively coupled plasma mass spectrometry (ICPMS) to characterise methylamphetamine hydrochoride Repetitive batches of samples were prepared using seven synthetic routes commonly used by clandestine chemists (149 samples in total) and analysed by each technique to provide a robust sample set of known provenance for data interpretation. Organic analysis of all samples was undertaken using a developed and partially validated GCMS impurity profiling method. Basic and acidic impurities were extracted separately and analysed using a DB-1 MS column. The GCMS method discriminated all routes based on a set of route specific target impurities determined through this project. This target set was compared with suggested literature impurities and better resolution was achieved. Furthermore, variations in impurity profiles reported in the literature were resolved through investigation of the respective synthetic processes. A comparison of the DB-1 MS with a DB-5 column and a single basic pH extraction method confirmed this as a viable alternative to many of the methods described in the literature. Stable isotope ratios (δ¹³C,δ¹⁵N,δ²H) were measured by elemental analyzer/thermal conversion isotope radio mass spectrometry (EA/TC-IRMS). This facilitated the differentiation of samples by starting material, with δ¹³C providing the best results. Inorganic impurities present in the samples were analysed by inductive couple plasma mass spectrometry (ICPMS). This facilitated some discrimination of the samples by synthetic pathway only. Pattern recognition techniques were applied to the generated data (raw and processed) from each analytical technique both individually and together. Pearson's correlation coefficient, hierarchical cluster analysis, principal component analysis and discriminate analysis were used to investigate the separation of the sample batches by starting material and synthetic route. These mathematical tools demonstrated that methylamphetamine profiling linking samples by starting material and/or synthetic route was achievable.This project evaluates the abilities of gas chromatography mass spectrometry (GCMS), isotope radio mass spectrometry (IRMS) and inductively coupled plasma mass spectrometry (ICPMS) to characterise methylamphetamine hydrochoride Repetitive batches of samples were prepared using seven synthetic routes commonly used by clandestine chemists (149 samples in total) and analysed by each technique to provide a robust sample set of known provenance for data interpretation. Organic analysis of all samples was undertaken using a developed and partially validated GCMS impurity profiling method. Basic and acidic impurities were extracted separately and analysed using a DB-1 MS column. The GCMS method discriminated all routes based on a set of route specific target impurities determined through this project. This target set was compared with suggested literature impurities and better resolution was achieved. Furthermore, variations in impurity profiles reported in the literature were resolved through investigation of the respective synthetic processes. A comparison of the DB-1 MS with a DB-5 column and a single basic pH extraction method confirmed this as a viable alternative to many of the methods described in the literature. Stable isotope ratios (δ¹³C,δ¹⁵N,δ²H) were measured by elemental analyzer/thermal conversion isotope radio mass spectrometry (EA/TC-IRMS). This facilitated the differentiation of samples by starting material, with δ¹³C providing the best results. Inorganic impurities present in the samples were analysed by inductive couple plasma mass spectrometry (ICPMS). This facilitated some discrimination of the samples by synthetic pathway only. Pattern recognition techniques were applied to the generated data (raw and processed) from each analytical technique both individually and together. Pearson's correlation coefficient, hierarchical cluster analysis, principal component analysis and discriminate analysis were used to investigate the separation of the sample batches by starting material and synthetic route. These mathematical tools demonstrated that methylamphetamine profiling linking samples by starting material and/or synthetic route was achievable

Investigation of the reaction impurities associated with methylamphetamine synthesized using the nagai method

The synthesis of methylamphetamine hydrochloride from l-ephedrine or d-pseudoephedrine hydrochloride via reduction with hydriodic acid and red phosphorus was investigated. Eighteen batches of methylamphetamine hydrochloride were synthesized in six replicate batches using three different reaction times. This allowed the investigation of the variation of impurities in the final product with reaction time. The results obtained have resolved previously conflicting impurity profile data reported in the literature for this synthesis route. The impurity profile was shown to change with reaction time and all previously. reported impurity components were identified but not in all batches. Additionally, 20 batches of methylamphetamine hydrochloride were synthesized from either from l-ephedrine or d-pseudoephedrine hydrochloride in reactions which were allowed to proceed for 24 h. The impurities present in the resulting batches were investigated, and route-specific impurities present in all batches were identified. Batch-to-batch fluctuations in the resultant chromatographic impurity profile, despite careful synthetic monitoring and control, were also noted

Clarification of route specific impurities found in methylamphetamine synthesised using the Birch method

This paper focuses on the determination of route specific impurities produced when methylamphetamine is synthesised using the Birch reduction. Previous work available in the scientific literature reported only one route specific impurity using ephedrine hydrochloride as the starting material. In this paper we investigated the impurity profiles of methylamphetamine produced from both the salt and base forms of ephedrine and pseudoephedrine. A new previously unreported route specific impurity was revealed as was the potential absence of the previously reported impurity in the profile of samples prepared from the free base

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