Identifying Synthetic Designer Drugs Using FT-IR, Raman, and GC–IR

Jul 31, 2014

Law enforcement relies upon "schedules" or lists of controlled substances. In an attempt to circumvent the law, clandestine laboratories produce synthetic designer drugs that are chemically related to a controlled substance, but are different enough to raise legal issues with prosecution. Identification of the drugs as evidence requires exact information, including isomeric and stereochemical specificity. We show here examples where infrared (including gas chromatography–infrared spectroscopy) or Raman spectroscopy paired with reference libraries can provide the needed specificity with the additional advantage of being fast.

Law enforcement agencies worldwide report increasing street supplies of synthetic drugs, including so-called "bath salts" and cannabinoids. The United States Drug Enforcement Administration (DEA) and other law enforcement agencies recently initiated a major raid targeting all levels of the global synthetic designer drug market (1). Small chemical modifications made to known drugs result in new drugs that may not be on federal or state controlled substance lists. Words in laws such as "analogue" tend to leave interpretation open to juries. Court cases may hinge on the exact positional or stereochemical isomer, which juries are likely not technically competent to assess. As laws tighten, convictions remain dependent on incisive forensic analysis.

The Scientific Working Group for the Analysis of Seized Drugs (SWGDRUG, defines infrared and Raman spectroscopy as two of a limited number of "Category A" analytical techniques providing the highest potential discriminating power (2). For seized-drug identification, it is most desirable to use a Category A technique combined with at least one other technique (Category A, B, or C). To assist forensics laboratories in the drug identification process, scientists at the Cayman Chemical Company, the Tennessee Bureau of Investigation (TBI), and Thermo Fisher Scientific collaborated to make high quality libraries of reference spectra (dispersive Raman, attenuated total reflection-infrared [ATR-IR], and vapor-phase IR) from synthetic designer drugs available. Here, we discuss the importance of Fourier transform infrared (FT-IR) and Raman spectroscopy, enabled by these libraries, in identifying designer drugs in seized materials (3). We also present how gas chromatography with IR detection (GC–IR) enables the identification of specific isomers of synthetic drugs even when present in complex matrices like plant material.


Figure 1: Comparison of FT-IR and Raman spectra from mephedrone, a psychoactive compound commonly known as "meow meow."
Reference Raman and FT-IR spectra were acquired using compounds obtained from Cayman Chemical Company. FT-IR spectra were acquired at 2 cm-1 resolution with a diamond ATR accessory integrated into a Thermo Scientific Nicolet iS50 FT-IR spectrometer. The Raman spectra were acquired on a Thermo Scientific DXR Raman system with 532-nm laser excitation, a 900-line/mm grating and a 25-μm slit. The Raman and infrared spectra acquired from a sample of mephedrone shown in Figure 1 demonstrate the complementary nature of these two techniques, which emphasize different functional groups in the molecule (4). In this example, we labeled the peak locations to allow easy comparison to the spectra in the SWGDRUG monographs.

GC–IR vapor-phase spectra were acquired at TBI. Standards of cannabinoids, bath salts, and other drugs were mixed with solvent (typically methanol) to obtain 1-mg/mL solutions.

A 5-m silica capillary with a 0.30-mm cross section coated with bonded poly(1% diphenyl, 99% dimethylsiloxane) was used. The temperature program was as follows: 80 °C for 1 min, then 70 °C/min from 80 °C to 270 °C, and 270 °C for 20 min. This combination of short column and fast ramp is used because the drugs have low volatility, which can lead to long retention times. Under these conditions, seized materials often exhibit incomplete separation (plant extracts and contaminants being present), necessitating further analysis as noted below. The resulting reference spectra were grouped into the TBI gas phase library.

Figure 2: Comparison of vapor-phase spectra for three closely related cannabinoids.
Figure 2 shows GC–IR results for three compounds that illustrate spectral differences among highly similar isomers. This ability to identify isomers is a major advantage of both IR and Raman spectroscopy.