Combating the New Psychoactive Substance (NPS) Wave with NMR and Raman Spectroscopies
Foredragsholder; Aaron Urbas, National Institute of Standards and Technology
Forensic laboratories commonly receive new psychoactive substances (NPSs) including synthetic opioids such as analogues of fentanyl as well as various other classes of psychoactive substances. These compounds are typically developed in an effort to stay ahead of drug scheduling laws banning their use and distribution and keeping pace with the identification of these compounds is becoming an increasing challenge for forensic labs. These analogues are constantly evolving and typically involve slight changes to chemical structures, e.g. shifting the position of functional groups such as methyl groups or halogens on the aromatic ring. Closely related isomers can be difficult to distinguish with traditional methods used for analysis, e.g. GC-MS. With other spectroscopic techniques such as nuclear magnetic resonance and vibrational spectroscopies it is often relatively straightforward to differentiate these compounds. However, other challenges impede the successful application of these techniques in forensic drug analysis.
NMR is a powerful tool for structure elucidation and quantitative analysis among other applications, but this technique is not practical in many forensic laboratories due to the cost of the instrumentation and maintenance. Recent work has shown the potential applicability of low-field NMR as an alternative in forensic drug analysis. These benchtop, semi-portable instruments are less costly, have a smaller footprint, do not use cryogens, and require little maintenance. We investigated the use of a benchtop low-field (62 MHz) 1H NMR spectrometer for differentiating 65 fentanyl and related substances, including various types of positional isomers, were readily differentiated with low-field (62 MHz) 1H NMR spectroscopy. In addition, we successfully demonstrated the use of quantum mechanical spin system analysis for the purposes of translating experimentally observed high-field 1H spectra to lower field strengths. This suggests the feasibility of developing field-strength independent 1H NMR spectral libraries to facilitate reference material data dissemination across forensic drug laboratories.
Differentiating NPSs based on their vibrational spectra is also fairly straightforward for relatively pure materials if a reference spectrum is available. Benefits of vibrational spectroscopy techniques include rapid sample analysis with little or no sample preparation requirements. With mixtures, however, the utility of these techniques can be greatly diminished. We are currently investigating the use of Raman spectroscopy for the identification of multiple constituents in mixtures with the aim of developing a non-targeted screening approach to seized drug. By exploiting compositional variations in powder mixtures at the micro-scale, estimates of pure spectra of constituents can be resolved using multivariate curve resolution (MCR) techniques. These pure component estimates can be utilized more effectively in library searches and detection limits can be significantly improved compared to mixture spectra from bulk spectroscopic analysis. Results with investigations using a fentanyl surrogate in blends with a variety of cutting agents and over-the-counter medications will be discussed.