Stability of selected substances related to the clandestine production of amphetamine-type stimulants in wastewater:Identification of transformation products

Environmental impact of toxic and corrosive synthesis waste generated by the clandestine production of amphetamine-type stimulants (ATS) is a known problem, which can even result in malfunction of wastewater treatment plants (WWTPs), e. g. in case of illegal discharge of large amounts of highly acidic chemical waste into the sewage system, which is generated in clandestine labs converting pre-precursors to the most prevalent ATS precursor benzyl methyl ketone (BMK). ATS synthesis-specific substances, precursor chemicals, intermediates and route-specific by-products may also support wastewater-based epidemiology (WBE) studies to explain abnormally high loads of drugs in wastewater by distinguishing whether these high loads were caused by consumption or disposal of synthesis waste into the sewage system. Although some of these synthesis-specific substances can be detected in traces in the final form of consumption of the product, these substances are removed from the drug product to a large extent during cleaning steps, e.g. the frequently applied steam distillation step to purify the amphetamine raw base after clandestine Leuckart synthesis. In contrast, these synthesis-specific by-products are very prominent in chemical synthesis wastes, whereby their detection in wastewater would prove a disposal of synthesis wastes instead of excretion after drug product consumption. As a prerequisite, such substances need to exhibit a certain chemical and biological stability in wastewater and, therefore, lab-scale experiments were performed in a mixture of WWTP effluent and activated sludge. Fourteen selected synthesis-specific substances, all related to the production of ATS, comprised pre-precursors (e.g. α-phenylacetoacetonitrile (APAAN) or α-phenylacetoacetamide (APAA)), precursors (e.g. BMK), intermediates (e.g. N-formylamphetamine (NFA)), synthesis by-products (e.g. N,N-di-(β-phenylisopropyl)amine (DPIA)) and final products (e.g. amphetamine (AMPH)). Stability of test substances was evaluated by targeted HPLC-MS/MS analysis, while HPLC-HRMS techniques were used for the identification of transformation products (TPs) of substances that have undergone primary degradation. All substances were detectable for five days minimum and seven out of 14 substances underwent at least primary degradation. A total of three TPs were identified: TP164 was formed by oxidation of ephedrine (EPHE) and was further transformed after maximum formation, while TP180-1 and TP180-2 were formed by reduction of APAA and both remained stable. This is the first study investigating the stability of ATS synthesis-specific substances in wastewater demonstrating sufficient stability for wastewater monitoring studies.