Screening suspect pharmaceuticals for illicit designer benzodiazepines using raman, SERS, and FT-IR prior to comprehensive analysis using LC-MS

Abstract

The emergence of illicit designer benzodiazepines with high dependency and no approved clinical use are of great US public health concern. Due to the increasing numbers of illicit designer benzodiazepines encountered in the US supply chain, there is a need to develop robust analytical methods that can rapidly detect these chemicals. Suspect counterfeit tablets, powders, or liquid formulations were first screened using Raman spectroscopy and surface-enhanced Raman scattering spectroscopy (SERS) for the presence of legal or illicit benzodiazepines, and then further analyzed using Fourier-transform infrared (FT-IR) spectroscopy and liquid chromatography with tandem mass spectrometric detection (LC-MS). Several microextraction procedures were developed and used to extract benzodiazepines from samples prior to SERS, FT-IR, and LC-MS analysis. Conventional Raman analyses using handheld Raman spectrometers afforded the ability to examine samples through enclosed plastic bags but were only able to detect high concentrations of various benzodiazepines in the suspect samples. The developed SERS methods were sufficient for detecting at least one benzodiazepine in the low-dose suspect samples, thereby allowing prioritization using other analytical tools that require more sample preparation and time-consuming analyses. The use of FT-IR spectroscopy coupled with extraction and spectral subtraction was found to be selective to multiple benzodiazepines and various excipients in the analyzed samples. This study demonstrated that the developed SERS and FT-IR procedures could be used in satellite laboratories to screen suspect packages at ports of entry and prioritize samples for additional laboratory-based analyses in an effort to prevent dangerous and illicit pharmaceutical products from reaching the US supply chain.