Characterization of Samples From a Seized Synthetic Drug Laboratory by Suspect and Nontarget Screening With LC‐HRMS—Identification of Markers Indicating Changes in the Clandestine Manufacturing Process of Amphetamine via the Leuckart Route

In clandestine laboratories, amphetamine is predominantly synthesized via the Leuckart route. In recent years, a trend is observed: Capacities of illicit production facilities for synthetic drugs in Europe increased and fewer small-scale laboratories are encountered by police and customs authorities. One of the designer pre-precursors currently applied is methyl α-phenylacetoacetate (MAPA), which can be converted into the key synthesis educt benzyl methyl ketone by acidic hydrolysis. Besides replacements of former designer pre-precursors due to scheduling (e.g., α-phenylacetoacetonitrile [APAAN]), another trend for synthesis is observed since 2019, namely, the alkaline hydrolysis of the reaction intermediate N-formylamphetamine into the free amphetamine base during the second step of the Leuckart route instead of the previously predominantly applied acidic hydrolysis using concentrated hydrochloric acid. In this study, 28 samples of products and production waste seized from a dismantled large-scale amphetamine laboratory in Germany that used MAPA as designer pre-precursor and the modified alkaline Leuckart step two were analyzed by a nontargeted liquid chromatography-high-resolution mass spectrometry approach for tentative identification of specific markers for the use of MAPA and the alkaline hydrolysis of N-formylamphetamine. After peak picking, 23 features were identified as suspects and further seven new features were tentatively identified. These seven potential marker compounds appeared to be indicative for the pre-precursor conversion step and were found in production waste and in amphetamine base product samples. Additionally, there were hints for the formation of high molecular weight compounds during the modified Leuckart step two.