Advances in benchtop nuclear magnetic resonance instrumentation have brought the benefits of NMR spectroscopy without the associated time and money costs, explains Jürgen Kolz – providing a useful weapon against drug trafficking.
The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) reports about one million seizures of illicit drugs annually, the vast majority of which are related to known substances such as cannabis, cocaine and opioids. However, drug enforcement authorities are also tasked with controlling a growing number of synthetic drugs or new psychoactive substances (NPS), which mimic the effects of illicit drugs, while evading legal restrictions.
To date, 141 countries and territories have reported to the United Nations Office of Drug Control Early Warning Advisory the emergence of 1,230 new psychoactive substances [1]. The EMCDDA was monitoring around 930 NPS at the end of 2022, 41 of which were first reported in Europe in 2022 [2].
Fentanyl and other synthetic opioids, including novel combinations, are fuelling a drug overdose epidemic in the US that killed more than 100,000 people in 2022 [3] and is rarely out of the media spotlight. Against this backdrop, authorities need to enhance their analytical toolset to quickly and reliably identify and quantify known and unknown substances, to help them to tackle the growing and increasingly complex – and lethal – drugs trade.
Introducing NMR
Nuclear magnetic resonance (NMR) spectroscopy is a powerful analytical technique widely used in chemistry, biochemistry and materials science for identification, structural characterisation, and quantification of compounds.
Traditional NMR spectrometers use large superconducting magnets to generate very strong magnetic fields to enhance the sensitivity and resolution of the measurement. However, these high-field instruments can be cost-prohibitive to purchase, run and maintain, and must be operated by specialist NMR technicians. These instruments are installed in a separate facility because they require a large amount of space and controlled handling. In forensics, these systems are usually only available in central labs, to which samples need to be sent away, causing unmanageable delays to sample analysis.
Advances in NMR technology have led to the development of benchtop NMR instruments in recent years, which use compact permanent magnets to generate the required magnetic field.
NMR gains attention in forensics
NMR Spectroscopy is recognised by The Scientific Working Group for the Analysis of Seized Drugs as a Category A analytical technique. Modern benchtop NMR systems are being adapted to suit the needs of regulated markets, such as forensics. NMR spectroscopy is inherently quantitative, therefore there is no need for timely and expensive calibration. What’s more, the identity and purity of a sample can be determined from one measurement.
Newly developed, extensive NMR spectra databases enable automatic identification of substances in a sample. For new substances (such as NPS), a range of advanced methods are used to elucidate the structure. Once the substance is identified it can be added to the spectra database for routine testing. Spectra databases are easy to expand and the whole database or defined entries can be easily selected to be shared with other systems.
NMR can enhance the complete analytical suite and be integrated with other spectroscopic techniques which are currently routinely used in forensic labs, namely – infrared spectroscopy, ultraviolet spectroscopy and GC/MS.
NMR in use
It can be difficult to determine how a drug was made using other methods, but it is possible with NMR. Products, starting materials and by-products can be easily identified and quantified. For example, the synthesis of methamphetamine often involves the reduction of ephedrine with red phosphorus and iodine. The phosphorus acids produced in the synthesis can be used to estimate how far through the synthesis the process was before being seized and on what scale it was being produced.
NMR can be used as further Category A evidence to support a proposed identity, and also to distinguish isomers or related compounds that may be difficult using GC-MS or IR spectroscopy. Figure 1 displays 1H NMR spectra of various psychoactive substances, each exhibiting a unique spectrum suitable for identification.
Furthermore, NMR can easily identify methylmethcathinone (MMC) isomers, found in real street samples (Figure 2). In addition, NMR spectroscopy is capable of distinguishing between related compounds, as exemplified in the case of heroin, where even slight alterations in chemical structure lead to readily observable changes in the spectra (Figure 3).
Conclusion
Customs and drug enforcement authorities around the world are facing multiple challenges and require fast, accurate means to detect and quantify illegal substances. Advances in benchtop NMR make it a useful tool in their analytical arsenal, with labs recognising its exceptional discriminating power and the fact that it is inherently quantitative. With a growing number of forensics labs benefiting from NMR, it is likely to be routinely adopted around the world in the coming months.
Head of application development at Magritek GmbH, Ju?rgen Kolz received a diploma in chemical engineering from Aachen University of Applied Sciences in 2004 before completing his PhD in chemistry, followed by a postdoctoral stay at the University of Cambridge
References:
1 https://www.unodc.org/LSS/Page/NPS
2 European Monitoring Centre for Drugs and Drug Addiction (2023), European Drug Report 2023: Trends and Developments, https://www.emcdda.europa. eu/publications/european-drugreport/ 2023_en
3 Centers for Disease Control and Prevention (2023), NCHS: A Blog of the National Center for Health Statistics, Provisional Data Shows U.S. Drug Overdose Deaths Top 100,000 in 2022 | Blogs | CDC