New psychoactive substances (NPS) are a complex addition to the international drug problem. They are intentionally developed to circumvent legislation and have been marketed as ‘legal highs’, thereby intimating they are safe alternatives to drugs such as ecstasy, methamphetamine, cocaine, and cannabis. Little or no toxicity information is available for these substances, and (co)-ingestion of these compounds has led to hospitalisation and fatalities. Due to the proliferation of these compounds – by January 2021, more than 1000 NPS had been reported to the United Nations Office of Drugs and Crime Early Warning Advisory (UNODC EWA) from 126 countries covering all continents – it is imperative to understand both use and toxicity of these substances.
The objectives of this work are fourfold:
- Identify unique metabolites of NPS. The most prevalent, based on data from the UNODC EWA, will be subjected to these experiments.
- Examine the toxicity of these metabolites and the parent drugs in in-vitro bioassays with a focus on neurotoxicity and cytotoxicity as presumed main modes of action.
- Investigate in-sewer stability of the drugs and identified metabolites.
- Include all identified metabolites and transformation products in new analytical methods, which will be applied to wastewater samples from Germany and Australia to evaluate their applicability for future screening purposes.
It is expected that the toxicity data and specific transformation products/metabolites identified by this project will facilitate future forensic investigations. Moreover, it will guide policy advisors to understand the risks of these substances.
Outcomes
This work is ongoing. However, the major outcome from the first year of this work was the identification of unique metabolites of several new psychoactive substances. In September 2022, Julia Huchthausen (UFZ, Germany) visited QAEHS (Australia). She brought her expertise in S9 incubation to simulate in vitro metabolism to help establish a method at QAEHS. A Standard Operating Procedure (SOP) was developed so that it can be used for future work. This method was applied to 11 new psychoactive substances. Two liquid chromatography–mass spectrometry (LC-MS) methods were then used to analyse the extracts for metabolites, with 17 metabolites initially identified.
