With new so-called designer drugs hitting the streets at a rate of up to 100 substances a year1 – which equates to two new products every week – drug testing is a constant battle. These new psychoactive substances (NPS), often also referred to as ‘legal highs,’ contain one or more chemical ingredients which mimic the effects of traditional drugs such as cocaine, cannabis or ecstasy.
While NPS might seem desirable to their underground market in offering new and unexplored highs, they in fact have a far darker purpose. Not only illegal in the UK and many countries worldwide, but they have also been specifically developed to dodge the drug screening systems that test for known substances – so can often enter a country undetected.
Keeping up with NPS presents a huge challenge to border control authorities and police forces across the globe, not least because their ability to avoid detection means these substances can rapidly flood a market. Furthermore, their effect on the body may be highly dangerous and, as unknown substances, their symptoms are difficult to recognize and treat. According to a report from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA),2 “The increasingly global reach of organized crime groups involved in drug production and trafficking represents a major cross-border security threat. They are forward-looking and quick to innovate in order to counter threats to their business model.”
Recent advances in analytical technologies, such as nuclear magnetic resonance (NMR) spectroscopy, are enabling testing laboratories to identify NPS and break the cycle, changing the way the entire drug screening market operates.
Current Testing Methods
There are two main objectives of drug identification: firstly to conduct immediate screening at the point of seizure, for example using handheld devices such as infrared spectroscopy, to indicate the likelihood of an illegal drug; and secondly, to generate evidence that provides proof of the composition of a drug by sending the seized material at a testing lab for identification and quantification. Providing unequivocal evidence is hampered by many issues.
The key problem is that the testing methods rely on libraries of known substances for drug analysis, which the illicit drug enterprises avoid by deliberately changing a drug’s molecular structure.
Organizations such as the EMCDDA, the European Network of Forensic Science Institutes (ENFSI) and the Customs Laboratories European Network (CLEN) are driving the adoption of a global database of substances. The maintenance of this database plays an essential role in the fight against illegal trafficking of drugs.
The most popular ploy to avoid detection is to adulterate the drug at the molecular level so that it cannot score positive in screening tests that check for known substances. Creating a mimic by switching small parts of a molecule means an NPS goes undetected and, without a positive match to the library of known substances, a drug cannot be identified. Faced with this growing problem, police forces and criminal investigators need a new way to track the unknown as well as the known.
Current drug testing primarily uses mass spectrometry (MS) screening. This tried and trusted method produces reliable results but is limited by the need to compare the spectral peak of the unknown substance with a reference substance and to display a known peak in the vicinity, i.e. a compound-specific reference standard. Any mimic molecule will display different fractural patterns in analysis and will slip through the scrutiny net.
The Solution is NMR
NMR spectroscopy systems are a well-established testing method in clinical research sectors, as well as forensic science at police, customs and border control labs. NMR can identify and quantify unknown substances without requiring a compound-specific reference. While MS systems are installed in many local laboratories, high-resolution NMR is only accessible at major scientific centers. According to a report from the European Commission, “The chemical identification of many unknown substances found by customs and suspected to be NPS requires the use of more sophisticated analytical techniques such as NMR.”3
The uptake of NMR has up until now been restricted by the high cost of ownership, as well as the technical expertise needed to operate NMR instrumentation for successful sample testing and analysis. Now, new benchtop models, like Bruker’s Fourier 80, are set to offer a rapid, automated, easy-to-use and unrestricted method of drug screening that is available for widespread and practical use.
Double Testing for Legal Scrutiny
In most countries, at least two orthogonal analytical methods must be used in drug testing to provide sufficient evidence that will stand up in court, which is both time consuming and resource-intensive. Where an NPS is identified, the second test method has to be NMR, which, given the low availability of high-resolution NMR instrumentation per country, leads to substantial sample bottlenecks at central scientific hubs.
Benchtop NMR, however, is set to change this. Once a new substance is identified, anywhere in the world, its spectral data can be uploaded into a global database, from where any lab across the globe with a similar benchtop NMR instrument could identify and quantify that substance at the touch of a button, using spectral fingerprinting. Using MS alone would not be feasible, as this approach would require designing a deuterated species of the substance and making the reference compound available to any lab, which, at a rate of two new NPS a week, is simply not possible.
Drug Quantification and Source Tracing
Drug quantification is also an important step in the analysis process when gathering evidence. In many countries, the penalty for possession of a drug that is cut, e.g. with 50 percent of a benign substance like ibuprofen, will be more lenient because of the purity of the drug – and therefore the amount possessed – is halved.
In addition, the cutting agent can provide important indications of the drug’s source and its trafficking pattern. Screening by MS can identify the agent, but quantifying this agent requires specific reference standards and is prohibitively resource-intensive in most cases. While conventional NMR instruments cannot be spared for this type of routine analysis, a benchtop NMR system can add value in this standard analysis without the need for reference standards, making pattern recognition in cutting agents a standard tool for providing evidence.
Identifying the Unknown
A major advantage of NMR screening is its ability to detect and identify unknown substances without needing a pre-qualified reference. Any mimic molecule is detected and displayed in the generated spectrum of results, where the drug composition can be deciphered in the spectral analysis. It is clearly revealed that, although the spectral fingerprint looks almost identical to the library match, one spectral isomer is different – and therefore the substance could be an NPS. This new substance can then be investigated further and added to the library for future immediate matching and identification.
Cutting Screening from Days to Minutes
The fast turnaround of NMR reduces screening time from days to minutes. In a situation where drugs have been seized, in any quantity, the amount of administration needed to hold a suspect for the length of time required for substance analysis – rather than the initial screen – may be prohibitive. Time-to-result for a benchtop NMR instrument, to deliver a conclusive identification, is dramatically shortened compared to conventional NMR analyses, where samples may need to be sent long distances to scientific hubs. Any airport or police authority, for example, can now own a suite of benchtop NMR instruments to deliver routine screening results rapidly using the global database, without needing highly trained operators to run the test and interpret the findings.
Unlike traditional large scale NMR instruments, benchtop models operate using a single plug socket, with no need to recharge with high maintenance cryogenics like helium. New benchtop NMR instruments offer a cryogen-free magnet design, making it accessible and cost-effective for any lab to provide the definitive results unique to NMR analysis.
Centralized Integration
The true potential of NMR can be unlocked when full-sized instruments can be integrated with benchtop systems. Operators familiar with NMR software can take control of the benchtop system without needing additional training, and an inexperienced NMR user can benefit from push-button interfaces and dedicated workflows.
Therefore, if an ambiguous sample identification is returned, NMR experts from a central scientific hub can log in to the system and help with parameter optimization and data processing issues – using a familiar software interface and set of protocols for ease of use. This level of integration opens up the exciting potential for global collaboration beyond the current drug library sharing – with the possibility of national workflow definitions and method harmonization, critical for evidence generation, with local users and the centralized control all working on the same system in real-time.
Decentralizing NMR analysis to put an instrument in every drug testing center not only opens up the potential to dramatically scale up throughput and deliver a faster time-to-result, but also frees up the centralized high specification laboratory instrument and operator expertise to work on more specialist testing.
Benchtop NMR Presents the Future
With bodies like EMCDDA stating one of their goals is to “Increase the ability of forensic science and toxicology laboratories to identify new substances, […] which requires support for training, resources for testing, and a mechanism for production and sharing of analytical data, reference materials and expertise,”2. Benchtop NMR instruments are well placed to support the new substance testing, data sharing and reference library creation to support this objective.
Dr. Joerg Koehler studied physics and holds a doctoral degree from the Institute of Biophysics and Physical Biochemistry of the University of Regensburg, where he had also worked as a Postdoctoral Research Scientist with focus on NMR based studies of folding intermediates of biochemically active macromolecules. Dr. Joerg Koehler held several positions in sales, sales management and business administration before joining Bruker as Head of Business Unit Industrial. Today he is accountable for Bruker’s global activities in magnetic resonance in various industrial market segments including forensics.
References
- Global Synthetic Drugs Assessment 2017, United Nations Office on Drugs and Crime, https://www.unodc.org/documents/scientific/Global_Drugs_Assessment_2017.pdf
- EU Drug Markets Report 2019, European Monitoring Centre for Drugs and Drug Addiction, http://www.emcdda.europa.eu/system/files/publications/12078/20192630_TD0319332ENN_PDF.pdf
- Report on Characterization of New Psychoactive Substances (NPS), European Commission, 2014 https://ec.europa.eu/jrc/sites/jrcsh/files/jrc-characterisation-new-psychoactive-substances_en.pdf with citation on page 4