Profiling ephedrine/pseudoephedrine and methamphetamine synthesised from benzaldehyde, nitroethane and dimethyl carbonate.

In previous work, a novel pathway for the synthesis of ephedrine/pseudoephedrine and methamphetamine using the precursors benzaldehyde, nitroethane and dimethyl carbonate was investigated, and an impurity profile presented. This paper presents chiral and stable isotope ratios of ephedrine/pseudoephedrine and methamphetamine synthesised by this pathway. Based on the chiral profile and the more negative δ13C (avg. -33.2‰) and more positive δ2H values, it is possible to distinguish ephedrine/pseudoephedrine and methamphetamine prepared from this pathway from those of "fully synthetic", "semi-synthetic" or "natural" origin. The more positive δ2H values of methamphetamine from this pathway allowed for differentiation from methamphetamine produced from phenyl-2-propanone. It was noted, however, that the use of stable isotope profiling would likely be limited when a benzaldehyde source having a negative δ2H value was used as a precursor. Furthermore, the stable isotope values alone could not be used to differentiate from methamphetamine prepared by the Akabori-Momotani reaction, highlighting the need for combination with impurity profiling.

Multi-drug cocktails: Impurities in commonly used illicit drugs seized by police in Queensland, Australia.

BACKGROUND: Impurities in commonly used illicit drugs raise concerns for unwitting consumers when pharmacologically active adulterants, especially new psychoactive substances (NPS), are used. This study examines impurities detected in illicit drugs seized in one Australian jurisdiction. METHODS: Queensland Health Forensic and Scientific Services provided analytical data. Data described the chemical composition of 9346 samples of 11 illicit drugs seized by police during 2015-2016. Impurities present in primary drugs were summarized and tabulated. A systematic search for published evidence reporting similar analyses was conducted. RESULTS: Methamphetamine was the primary drug in 6608 samples, followed by MDMA (1232 samples) and cocaine (516 samples). Purity of primary drugs ranged from ∼30% for cocaine, 2-CB and GHB to >90% for THC, methamphetamine, heroin and MDMA. Methamphetamine and MDMA contained the largest variety of impurities: 22 and 18 variants, respectively. Drug adulteration patterns were broadly similar to those found elsewhere, including NPS, but in some primary drugs impurities were found which had not been reported elsewhere. Psychostimulants were adulterated with each other. Levamisole was a common impurity in cocaine. Psychedelics were adulterated with methamphetamine and NPS. Opioids were quite pure, but some samples contained methamphetamine and synthetic opioids. CONCLUSIONS: Impurities detected were mostly pharmacologically active adulterants probably added to enhance desired effects or for active bulking. Given the designer nature of these drug cocktails, the effects of the adulterated drugs on users from possible complex multi-drug interactions is unpredictable. Awareness-raising among users, research into complex multi-drug effects and ongoing monitoring is required.

Enantiomeric profiling of amphetamine and methamphetamine in wastewater: A 7-year study in regional and urban Queensland, Australia.

Enantiomeric profiling was used in this study to investigate the consumption of amphetamine and methamphetamine in regional and urban Southeast Queensland, Australia over a period of seven years. S(+) methamphetamine was predominantly consumed in both urban and regional areas, showing a two and three fold increase in urban and regional catchments respectively between 2011 and 2017. The ratio of amphetamine to methamphetamine (AMP/METH) in wastewater reflected the expected excretion profile of methamphetamine consumption indicating the presence of amphetamine in this study was primarily the result of methamphetamine metabolism. However, the occasional occurrence of R(-) amphetamine in samples containing higher AMP/METH ratios, suggested the consumption of racemic amphetamine. The R(-) methamphetamine enantiomer was also identified in several samples, possibly indicative that the phenyl-2-propanone (P2P) synthesis process rather than the more typical reduction of ephedrines was also being used to manufacture methamphetamine. Furthermore, we identified two samples with a significantly different enantiomer ratio for the METH and AMP as well as a much lower AMP/METH concentration ratio suggesting contribution from direct disposal of methamphetamine into the sewer. This study demonstrated that enantiomeric profiling in wastewater-based epidemiology can provide valuable information for evaluating the origin of amphetamine in wastewater as either a metabolite of methamphetamine consumption or amphetamine itself.

Investigation of the l-phenylacetylcarbinol process to substituted benzaldehydes of interest.

The large scale industrial manufacture of the nasal decongestant pseudoephedrine is typically carried out by the reductive amination of l-phenylacetylcarbinol (l-PAC), which in turn is produced via the biotransformation of benzaldehyde using yeast. In recent years there has been increasing legislative control of the supply of pseudoephedrine due to it being diverted for the clandestine production of methylamphetamine and there is some evidence that a number of clandestine drug laboratory chemists have considered the application of the l-PAC process to manufacture their own pseudoephedrine. This work examined the use of a number of substituted benzaldehydes for the manufacture of the corresponding substituted l-PAC analogue followed by reductive amination to the corresponding substituted pseudoephedrine/ephedrine analogues. These substituted pseudoephedrine/ephedrine analogues were either reduced or oxidised to determine the feasibility of producing the corresponding methylamphetamine or methcathinone analogues. As a result, the l-PAC process was identified as a viable route for synthesis of substituted methylamphetamines and methcathinones.