A Detailed Mechanistic Fragmentation Analysis of Methamphetamine and Select Regioisomers by GC/MS

Abstract

A novel ring-substituted methamphetamine regioisomer, N,alpha,4-trimethyl phenmethylamine, was synthesized in order to study the validity of proposed structures for various mass spectrometry (MS)-derived peaks in a methamphetamine fragmentation pattern. While other research efforts have studied aspects of methamphetamine in detail, a full fragmentation study has not been reported previously. In addition to showing molecular structures represented by fragment peaks, mechanisms for selected processes are detailed. An empirically derived procedure to easily determine by simple spectral peak pattern recognition the geometry of dimethyl- or ethyl-substituted immonium ions (RRC = N+ RR) where m/z = 58 is outlined. These results are platform independent for electron ionization (EI) instruments, but have also proven to be helpful in explaining spectral peaks observed in spectra from ion trap systems. The spectrum for the synthesized methamphetamine regioisomer was accurately predicted using this methodology. While this approach is useful in some casework, the converse may be more useful: when an unexpected or unusual peak pattern arises in a spectrum, being able to analyze it to determine the structure of the molecule. This paper gives an analyst the means to begin such retro-synthetic analyses.

Atmospheric identification of active ingredients in over‐the‐counter pharmaceuticals and drugs of abuse by atmospheric pressure glow discharge mass spectrometry (APGD‐MS)

“…Figure (b) shows the APGD mass spectrum of methamphetamine, which has a prominent protonated molecule at m/z 150. Characteristic fragment ions were observed at m/z 134 (loss of CH 4 from [M + H] + ) and 58 . It should be noted that this sample of seized methamphetamine contains ephedrine and the mass spectrum of pseudoephedrine (Fig.…”

Impurity Profiling of Amphetamine and Methamphetamine Using Gas Chromatography Mass Spectrometry (GCMS) Harmonised Methods

“…In this context it is pertinent to indicate here that this approach of tentative identification has been generally gaining acceptance within the body of literature (Bachs & Woo 2007;Inohue et al 2008;Kunalan et al 2009;Puthaviriyakorn et al 2002;Qi et al 2007Qi et al , 2006. The chromatographic profiles of the methamphetamine samples ( Figure 5) were evidently 'cleaner' with low abundance of impurities (Table 2) when compared to that of the amphetamine samples.…”

“…Further examination of the spectral data of the impurity peaks showed vital information regarding possible synthetic route of the amphetamine samples although not all of the impurity peaks were successfully identified. Some of the impurities were identified by comparing their mass spectral information against the hydrocarbon mass spectral database (NIST-version 2.0f) available in the GC-MS system as well as related literatures (Allan & Ely 2011;Andersson et al 2007a;Bachs & Woo 2007;Cole 2003;Inohue et al 2008;Kunalan et al 2009;Puthaviriyakorn et al 2002;Qi et al 2006;Verweij 1989). Identification of these impurities has helped to point out several important markers that are specific to drugs synthesized via certain routes.…”

“…Impurities peaks were integrated for normalisation against the eicosane (C20) internal standard peak area. Identifications of the peaks were made using the National Institute of Standards and Technology (NIST) mass spectral database (version 2.0f) (NIST 2008) available in the GC-MS system and also using previous literatures (Allan & Ely 2011;Andersson et al 2007a;Bachs & Woo 2007;Cole 2003;Inohue et al 2008;Kunalan et al 2009;Puthaviriyakorn et al 2002;Qi et al 2006;Verweij 1989).…”

GC–MS and GC–IRD analysis of 2-, 3- and 4-methylmethamphetamine and 2-, 3- and 4-methylamphetamine

“…The base peak of m/z 58 is due to the formation of the immonium ion from the amine initiated a-cleavage. This is a characteristic ion for secondary amines of the amphetamine class of compounds and also results in the formation of the methylbenzyl fragment at m/z 105 [20]. The other fragments of note are m/z 91 due to the methylphenyl ion, m/z 77 from the phenyl ion and m/z 148 due to the loss of the a-methyl from the amineinitiated alpha-cleavage [21].…”