A trace processing impurity found in certain methamphetamine exhibits was isolated and identified as trans-N-methyl-4-methyl-5-phenyl-4-penten-2-amine hydrochloride (1). It was determined that this impurity was produced via reductive amination of trans-4-methyl-5-phenyl-4-penten-2-one (4), which was one of a cluster of related ketones generated during the synthesis of 1-phenyl-2-propanone (P2P) from phenylacetic acid and lead (II) acetate. This two-step sequence resulted in methamphetamine containing elevated levels of 1. In contrast, methamphetamine produced from P2P made by other methods produced insignificant (ultra-trace or undetectable) amounts of 1. These results confirm that 1 is a synthetic marker compound for the phenylacetic acid and lead (II) acetate method. Analytical data for 1 and 4, and a postulated mechanism for the production of 4, are presented. Copyright © 2015 John Wiley & Sons, Ltd.

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Chemicals that are available from renewable resources typically contain heteroatoms that make hydrogen bonding a prominent intermolecular interaction. We are examining how hydrogen bonding can be exploited as an adsorption mechanism to facilitate the recovery and separations of oxygenated aromatic compounds from renewable resources. Specifically, we examined the adsorption of compounds that have weak or attenuated hydrogen-bonding abilities. The solvent in our study was hexane, which is commonly used in the food industry to extract chemicals from plant material (e.g., for vegetable oils and flavor extracts). The low dielectric constant of hexane also facilitates the hydrogen-bonding adsorption mechanism. Three polymeric adsorbents of differing basicities were studied, an acrylic ester sorbent (XAD-7, Rohm and Haas), a pyridine sorbent (Reillex 425, Reilly Industries), and a tertiary amine sorbent (IRA-93, Rohm and Haas). Adsorption affinities (related to the adsorption equilibrium constant, K eq ) and adsorption enthalpies (-∆H°) were observed to increase with increasing basicity of the sorbent's binding site. Infrared spectroscopy was used to study the interaction mechanism between the solutes and small-molecule analogues of the binding sites for the three sorbents. These studies support the conclusion that the observed increase in adsorption results from increased hydrogen-bond strengths. These results indicate that, by adjusting the hydrogen-bond accepting abilities of the adsorbent, it is possible to alter adsorption affinities to balance the dual objectives of recovery and selectivity.

The analysis of organic impurities plays an important role in the impurity profiling of methamphetamine, which in turn provides valuable information about methamphetamine manufacturing, in particular its synthetic route, chemicals, and precursors used. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is ideally suited for this purpose due to its excellent sensitivity, selectivity, and wide linear range in multiple reaction monitoring (MRM) mode. In this study, a dilute-and-shoot UHPLC-MS/MS method was developed for the simultaneous identification and quantitation of 23 organic manufacturing impurities in illicit methamphetamine. The developed method was validated in terms of stability, limit of detection (LOD), lower limit of quantification (LLOQ), accuracy, and precision. More than 100 illicitly prepared methamphetamine samples were analyzed. Due to its ability to detect ephedrine/pseudoephedrine and its high sensitivity for critical target markers (eg, chloro-pseudoephedrine, N-cyclohexylamphetamine, and compounds B and P), more impurities and precursor/pre-precursors were identified and quantified versus the current procedure by gas chromatography-mass spectrometry (GC-MS). Consequently, more samples could be classified by their synthetic routes. However, the UHPLC-MS/MS method has difficulty in detecting neutral and untargeted emerging manufacturing impurities and can therefore only serve as a complement to the current method. Despite this deficiency, the quantitative information acquired by the presented UHPLC-MS/MS methodology increased the sample discrimination power, thereby enhancing the capacity of methamphetamine profiling program (MPP) to conduct sample-sample comparisons.