Application of Benchtop NMR Spectroscopy in Illicit Substance Analysis: A Focus on MDMA

At a time when the devastating impact of drug misuse is felt deeply by individuals and society at large, there is an undeniable need for both qualitative and quantitative analyses of illicit substances. Public Health England's data reveals the extensive costs incurred by the United Kingdom, covering areas such as healthcare services, law enforcement, fatalities, and drug-related crimes. One drug that remains a significant concern is 3,4-methylenedioxymethamphetamine (MDMA), commonly known as 'ecstasy.' Particularly among young adults and in nightlife settings, MDMA is one of the most popular substances. With dosing (amount MDMA per tablet) have been increasing steadily over the past decades accompanying the risks of overdosing, accurate analysis of this substance is vital. The quantification of MDMA in tested products serves as a cornerstone for harm reduction strategies, allowing healthcare professionals and law enforcement agencies to monitor trends in MDMA misuse closely. In a context where many young and inexperienced users may not understand the associated risks, education emerges as a key strategy for reducing drug-related fatalities and hospitalizations. On-site drug analysis can be crucial in this respect. The growing global focus on drug testing initiatives further emphasizes the urgent necessity for accessible, accurate analytical methods.

To confront these challenges effectively, the adoption of advanced analytical techniques becomes indispensable. Among these techniques, Nuclear Magnetic Resonance (NMR) stands out as a potent yet underutilized tool, particularly in the analysis of substances like MDMA.

In response, we embarked on a collaborative venture with TICTAC Communications Ltd (TICTAC) and the Abbate’s group at King’s College London. Our primary objective was to develop and validate a quantitative analytical method for MDMA with a special focus on testing 100 tablets as collected from music festivals in the UK. This approach leverages an internal calibrant alongside a Nanalysis 60 MHz benchtop NMR spectrometer, as demonstrated in Figure 1, which showcases a 60 MHz ¹H NMR spectrum of MDMA and ethylene carbonate as the internal calibrant.

Figure 1. 60 MHz ¹H NMR spectrum of MDMA crystal sample in DMSO-d₆, containing ethylene carbonate (EC) and D₂O. The integration areas of the methylene signal (1) for MDMA and resonance (2) for EC were chosen for qNMR analysis.

The major discoveries within this paper can be summarized as follows:

1. MDMA emerges as the most frequently detected synthetic drug at festivals and nightclubs, as per data collected by TICTAC from amnesty bin drug analysis projects.

2. The qNMR method developed in the study proves highly selective and specific for MDMA, even in the presence of known adulterants and cutting agents commonly found in MDMA tablets.

3. The method showcases exceptional linearity, accuracy, and precision, with results consistently meeting the United Nations Office on Drugs and Crime (UNODC) guideline acceptance criteria.

4. The study substantiates the method's robustness by analyzing 100 seized MDMA tablets with varying MDMA content, including low-dosage tablets, tablets with cutting agents, and tablets seized in different years.

5. Within-batch variation analysis reveals significant differences in MDMA content among tablets from the same batch, highlighting potential risks for users who dose based on prior experiences.

6. The study uncovers a substantial increase in the median MDMA content in tablets between 2018 and 2019, followed by a decline in 2021. Some 2021 tablets also contain other synthetic stimulants, adding complexity and potential dangers for users.

7. Our research provides valuable insight into the evolving MDMA market and underscores the importance of accurate quantitative analysis methods for ensuring user safety.

These findings offer a mere glimpse into the intriguing revelations unveiled in our research. If your curiosity beckons you to delve deeper into the fascinating realm of MDMA analysis, we invite you to explore the full paper for a comprehensive journey through our findings. Alternatively, for those seeking a quick and straightforward method to quantify MDMA in ecstasy tablets, our application note provides step-by-step guidance.