The good, the bad and the ugly

In the battle against illicit ‘designer drugs’, enforcement agencies need analysis beyond GC-MS

Drug enforcement agencies are often called upon to investigate clandestine synthesis labs, like the so called ‘meth-labs’, where there is a high probability of illegal substances being present. These laboratories usually contain large amounts of impure chemicals suspected of including illegal substances. Thus, drug enforcement measures require separation and identification of the components of the impure mixture. The court case stemming from the investigation will often hinge upon both the identity and quantity of illegal material present, and is therefore an extremely important consideration.

Clandestine laboratories have become increasingly sophisticated, being able to synthesize many prescription drugs (like hydrocodone, a key ingredient in Vicodin) or ‘designer drugs’, which typically involve slight chemical modifications of known materials. The class of drugs similar to ephedrine, for instance, includes methamphetamine and pseudoephedrine, one a controlled drug, the other an over-the-counter decongestant. These subtle differences make the need for a rapid, structurally sensitive method of analysis an imperative for effective drug law enforcement.

[caption id="" align="alignleft" width="300" caption="Figure 1: The mass spectrum of ephedrine and pseudoephedrine showing the identical mass peak patterns each produce"][/caption]

The biological activity of a chemical can change profoundly with even a small modification in the stereochemistry – the specific arrangement of chemical species about a central atom. The extreme importance of this became apparent with the drug thalidomide in the 1960s. Rotation of the chemical structure about a single bond changed the material from having a desirable, sedative effect (the “R+” form) to having horrific teratogenic effects (the “S-” form). A similar pair of compounds of interest in drug enforcement circles is ephedrine and pseudoephedrine, which differ only in the orientation of a side chain on one carbon atom. The first step in most analyses of drug materials is a separation, where individual components are broken out from the mixture. Gas or liquid chromatography is commonly used for separation. The now-separated materials are present only in tiny quantities, so very sensitive detectors are needed. Common ones like the flame-ionisation detector or the thermal conductivity detector are sensitive, but do not provide any insights into the structure - “something went through, but I don’t know what”. The most common structurally sensitive identification tool is a mass spectrometer (MS), which, when coupled to a gas chromatograph (GC-MS), is extremely sensitive and provides excellent identification power, with one major exception in drug analyses (Figure 1).

[caption id="" align="alignright" width="270" caption="Figure 2: By combining GC and FT-IR, the molecular structure of the components of a mixture can be determined"][/caption]

The MS works by shattering the molecule into components, and then measuring the mass of those components. The fragmentation pattern is reproducible for a given molecule, so the pattern of mass peaks can be used to identify many materials. However, when ephedrine and pseudoephedrine are fragmented, the patterns are identical, as seen in Figure 1. As an analogy, when a Lego toy is built with ten blocks, specific structures can be built – there are many possible configurations of those ten blocks. However, when broken apart, there is no way to determine the orientation of the blocks in the structure which had been built last. To determine this, the structure must be examined while it is still together.

The combination of GC with FT-IR, shown in Figure 2, provides just such a tool. The effluent of the GC column, with the separation complete, is directed onto a light pipe through which IR radiation has been directed. The FT-IR is a powerful gas analyser, with the capacity to detect trace quantities of gas, so the sensitivity needed to detect the material is present. The IR spectrum detects the structurally-intact form of the drug, and even subtle differences are detectable. Thus, the analysis of suspicious materials containing ephedrine or pseudoephedrine can proceed.

The combination of GC and FTIR provides a powerful tool for analysis of mixtures. While not as sensitive as GC-MS, the GC-IR method provides structural information about the intact molecule, enabling an analysis of the stereochemistry. In addition, the IR bench itself provides access to other powerful tools (microscopy, ATR, Raman) which can greatly extend the capabilities of the forensics laboratory.

References 1. Griffiths, P.R.; DeHaseth, J.A. Fourier Transform Infrared Spectrometry (Wiley & Sons, 1986), Chapter 18. By Michael Bradley, Applications Scientist, Thermo Electron Corporation, USA.