The Identification of Impurities in Illicit Methamphetamine Exhibits by Gas Chromatography/Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy

Abstract

Methamphetamine, a drug frequently abused in the United States, is often manufactured illicitly. One method commonly employed for this purpose is the Leuckart reaction, which is initiated with methyl benzyl ketone (IV) and either methylamine (I) and formic acid (II) or N-methylformamide (III), producing N-formylmethamphetamine (IX) as an intermediate [1]. Hydrolysis of IX with a strong acid such as hydrochloric acid produces methamphetamine (VI). (See Table 1 for a list of abbreviations and Fig. 1 for corresponding structures.) As the synthesis proceeds, various impurities are accumulated: reactants, byproducts, and intermediates, as well as contaminants arising from within the reagents themselves. The identification of such impurities thus far encountered in this laboratory by gas chromatography/mass spectrometry (GC/MS) and nuclear magnetic resonance (NMR) spectroscopy will be the subject of this discussion.

Analysis of the impurities in the methamphetamine synthesized by three different methods from ephedrine and pseudoephedrine

“…The methamphetamine dimer (3) and following four peaks (4-7) co-precipitated with methamphetamine in the crystallization process, and were detected in the GC chromatograms of all of the Emde samples after crystallization. Some of these peaks (3,4,6,7) were detected in two of the Moscow samples (M4 and M5). Cantrell et al [12] have identified naphthalene compounds as impurities in methamphetamine synthesized by the hydriodic acid/red phosphorus method.…”

“…All of the Emde samples (E1-E5) were classified into the first group, and were characterized by the five peaks including methamphetamine dimer (3)(4)(5)(6)(7). Some of the peaks (3,4,6,7) were detected in two of the Moscow samples (M4 and M5), and were classified as the second group. Two of the Nagai samples (N5 and N6) were characterized by the five peaks including naphthalene compounds (1, 2 and 8-10), and classified in the third group.…”

“…They can be classified mainly into two categories according to the precursors, 1-phenyl-2-propanone [4][5][6][7] and ephedrine compounds [8][9][10][11][12][13][14]. Both are generally used as precursors, and the latter is more widely used in the clandestine laboratories.…”

New impurity profiles of recent Australian imported ‘ice’: Methamphetamine impurity profiling and the identification of (pseudo)ephedrine and Leuckart specific marker compounds

“…Methamphetamine impurities arising via the Leuckart route have been examined extensively, especially in the 1970s and early 1980s [3,[20][21][22]. N-Formylmethamphetamine (V), N,N-di-(b-phenylisopropyl)amine (XII), N,N-di-(b-phenylisopropyl)-methylamine (XIII) and N,N-di-(b-phenylisopropyl)formamide (XV), which were identified in the recent AFP 'ice' samples ( Fig.…”

“…According to Kram and Kruegel [22], N-formylmethamphetamine (V), an intermediate in the Leuckart synthesis, is the only impurity that can be specifically associated with this route. However, in this study V is identified in most of the recent AFP 'ice' samples, despite the presence of the aziridines (Ia and Ib) and/or naphthalenes (VIII and IX) indicating an ephedrine origin.…”