Identification of specific markers for amphetamine synthesised from the pre‐precursor APAAN following the Leuckart route and retrospective search for APAAN markers in profiling databases from Germany and the Netherlands

Abstract

α-Phenylacetoacetonitrile (APAAN) is one of the most important pre-precursors for amphetamine production in recent years. This assumption is based on seizure data but there is little analytical data available showing how much amphetamine really originated from APAAN. In this study, several syntheses of amphetamine following the Leuckart route were performed starting from different organic compounds including APAAN. The organic phases were analysed using gas chromatography-mass spectrometry (GC-MS) to search for signals caused by possible APAAN markers. Three compounds were discovered, isolated, and based on the performed syntheses it was found that they are highly specific for the use of APAAN. Using mass spectra, high resolution MS and nuclear magnetic resonance (NMR) data the compounds were characterised and identified as 2-phenyl-2-butenenitrile, 3-amino-2-phenyl-2-butenenitrile, and 4-amino-6-methyl-5-phenylpyrimidine. To investigate their significance, they were searched in data from seized amphetamine samples to determine to what extent they were present in illicitly produced amphetamine. Data of more than 580 cases from amphetamine profiling databases in Germany and the Netherlands were used for this purpose. These databases allowed analysis of the yearly occurrence of the markers going back to 2009. The markers revealed a trend that was in agreement with seizure reports and reflected an increasing use of APAAN from 2010 on. This paper presents experimental proof that APAAN is indeed the most important pre-precursor of amphetamine in recent years. It also illustrates how important it is to look for new ways to identify current trends in drug production since such trends can change within a few years.

Characterisation of aqueous waste produced during the clandestine production of amphetamine following the Leuckart route utilising solid‐phase extraction gas chromatography–mass spectrometry and capillary electrophoresis with contactless conductivity detection

“…13 Sample 10,11GLeu2 was a mixture of the aqueous waste samples from batches 10 and 11. The only differences were that sodium hydroxide solution was used for the phase separation in Leuckart step 1 and that a vacuum distillation was used for the purification at the end instead of a steam distillation.…”

“…It is, however, crucial to consider that the composition will change when synthesis waste comes into contact with soil or wastewater due to microbial degradation. 12,13 This 2-step process starts with the conversion of the controlled precursor benzyl methyl ketone (BMK) to N-formylamphetamine (N-FA) which is hydrolysed to amphetamine in a second step. 2 The market is dominated by large-scale producers who have access to the required chemicals and equipment.…”

“…8 Due to its simplicity, the most common method for the amphetamine production in clandestine laboratories is the Leuckart reaction. 8,13,15 The reaction scheme to produce amphetamine sulphate starting from APAAN is shown in Figure 1. 14 Producers try to minimise the possibility of detection by using non-scheduled chemicals called pre-precursors to synthesise controlled precursors like BMK.…”

“…Several procedures are available to simultaneously analyse anions and cations using CE and an overview on this topic was given by Sáiz et al in 2014. Reaction step 3 consists of 2 parts with the first being the reaction of N-FA with hydrochloric acid (③a) and the second being the addition of sodium hydroxide to release the amphetamine freebase (③b) 13 The presence of organic compounds in clandestine waste is another important piece of information. This method was first developed independently in 1998 by Kubáň et al 17 and Padarauskas et al 18 and an overview on dual injection methods is given by Priego-Capote et al 19 In 2002, Kubáň et al published a method to separate up to 22 anions and cations using a capacitively coupled contactless conductivity detector (C 4 D) and this method was adapted and further optimised for the ion quantitation of aqueous synthesis waste samples within this work.…”

“…16 Of the different methods covered in their review, the dual opposite end injection (DOEI) was chosen for the synthesis waste analysis. 13 Organic compounds are used for the profiling of amphetamine using gas chromatography-mass spectrometry (GC-MS) and can provide information about the applied synthesis procedure and the reaction conditions. 20 FIGURE 1 Reaction scheme of the synthesis of amphetamine sulphate starting from APAAN.…”