The flying squad! Designer drugs and how to beat them

New ‘designer drugs’ are constantly emerging, and this presents increased challenges for forensic toxicologists involved in drugs of abuse screening. Here, Tony Drury discusses the use of time-of-flight MS to help detect this stream of new drugs

The illicit drugs scene is changing. In addition to ‘traditional’ drugs of abuse, such as cannabis and cocaine, there is a global move towards ‘designer drugs’, new synthetic substances commonly sold in head shops and chat rooms. New psychoactive substances are constantly emerging, and this presents increased challenges for forensic toxicologists involved in drugs of abuse screening.

‘Designer drugs’ are a set of synthetic substances which are formulated to mimic the chemical properties of certain drugs of abuse (DOA), such as cannabis and cocaine. The most popular group of substances, synthetic cannabinoids, consists primarily of plant material impregnated with psychoactive substances that mimic THC, the psychoactive substance in cannabis. In an attempt to avoid anti-trafficking laws, designer drugs are often labeled as innocuous substances such as ‘plant food’ or ‘bath salts’ and marketed through social media, chat rooms and in head shops.

Global use of designer drugs has increased significantly in recent years and every month several new psychoactive substances emerge onto the recreational drug use market. In an attempt to circumvent detection, manufacturers constantly create analogues and homologues of existing substances, subtly changing the chemical structure slightly whilst maintaining similar psychoactive effects. The UN Office on Drugs and Crime (UNODC) reported that 348 new so-called ‘legal highs’ were being used worldwide from 2009 to 2013.¹

[caption id="attachment_42395" align="aligncenter" width="600"] Figures 1a and 1b: Overlayed chromatograms for case number 954 at Helsinki. Presence of alprazolam is confirmed through QI traces and in bbCID spectrum.[/caption]

This trend is impacting the drug screening conducted by both government and commercial laboratories. Four leading screening companies in the UK recently reported significant increases in the number of drugs tests conducted for employers, which now commonly include testing for designer drugs.² The challenge facing forensic toxicologists is the need to detect new compounds as soon as they appear. Moreover, tests must produce irrefutable evidence of drug use that can stand up in court if needed. Methods are needed that can provide rapid wide range screening, with the elimination of false positives and false negatives for reliable results.

Traditional immunoassay technologies are unable to detect many designer drugs and are effectively blind to the ever-emergent novel psychoactive substances. Instead, the inherent characteristics of accurate mass make it an ideal tool for this application; the technique provides sensitive wide scope screening together with retrospective and general unknown analysis capabilities. High resolution time of flight mass spectrometry (UHR-TOF MS) has been in use for forensic and toxicological screening for several years. A solution has been developed that utilises UHR-TOF MS and includes a comprehensive database of forensic compounds for comprehensive screening. Additionally this solution incorporates the qualifier ions for enhanced result confirmation, in order to efficiently reduce false positives.

[caption id="attachment_42397" align="aligncenter" width="600"] Figure 2: Overlayed chromatograms from post-mortem urine, case GS 250 at Freiburg. Additional findings of amphetamine and carboxy-THC were confirmed with additional fragment traces or QI traces.[/caption]

The following examples demonstrate the use of UHR-TOF MS in conjunction with the database to test authentic forensic toxicology samples, provided by the University of Helsinki and the University of Freiburg. At Helsinki, urine samples from autopsy cases were analysed, while at Freiburg urine or serum samples from post-mortem and roadside testing cases were tested. The results were then compared to those from established screening methods, including ultra performance liquid chromatography time of flight (UPLC-QTOF), gas chromatography mass spectrometry (GC-MS), liquid chromatography mass spectrometry (LC-MS) and liquid chromatography mass spectrometry with ion trap technology (LC-MSⁿ ion trap).

Samples were analysed at both sites in broad-band CID (bbCID) data acquisition mode (regular and fast switching between high and low collision energy settings resulting in simultaneous fragmentation of all ions present). Results were compared to a screening database containing name, sum formulae and retention time (RT), as well as alternative ions (fragments, adducts) with a relative intensity >10%. Additional entries for an M+1 or M+2 isotope of each compound were included, and fragment ions observable in the bbCID data were collected as qualifier ions (QI) for result confirmation.

The results for the authentic case samples were in good agreement with findings from routine analysis. The ‘qualifier ion’ concept is a powerful tool to remove false positive findings, resulting in a robust screening method with a low detection threshold and wide retention window for avoiding false positives.

As the growth and continual emergence of designer drugs continues, forensic toxicologists must have access to screening techniques to reliably detect these new substances. New approaches are vital to provide reliable evidence of these ever-emergent new psychoactive substances. This solution, using high resolution accurate mass detection with an extensive database of forensic compounds, delivers high sensitivity, wide scope screening whilst minimising false positives and negative detection rates, delivering high confidence in the end results.