Flipped detection of psychoactive substances in complex mixtures using handheld Raman spectroscopy coupled to chemometrics

• Published in: Journal of Raman spectroscopy 2022-08, Vol.53 (8), p.1428-1444
• Main Authors: Calvo‐Castro, Jesus, Tchakounte, Steve N., Guarino, Valentina, Ahmed, Adeel A., Stair, Jacqueline L.
• Format: Article
• Language: English
• Subjects: Adulterants; Algorithms; Analytical chemistry; chemometrics; complex mixtures; design‐of‐experiments; Mixtures; new psychoactive substances (NPS); Portability; Principal components analysis; Raman spectroscopy; Spectral signatures; Spectroscopy; Spectrum analysis; Target detection
• ISSN: 0377-0486; 1097-4555
• DOI: 10.1002/jrs.6372

New psychoactive substance (NPS) misuse represents a critical social and health problem. Herein, a novel flipped approach is presented for the detection of psychoactive substances in complex mixtures using portable Raman spectroscopy. This consists firstly of evaluating the spectral dissimilarities of an NPS product to its constituent adulterants followed by detection of the NPS by means of key spectral signatures. To demonstrate it, three structurally diverse NPS and four commonly used adulterants were selected. A Design‐of‐Experiments guided approach was employed to determine the composition of simulate street samples, ranging from binary to quinary mixtures of varying concentrations. Spectra were acquired for all mixtures using a portable Raman spectrometer and examined using projection analysis on model systems, developed via principal component analysis using reference materials. For all 21 mixtures investigated, the innovative ‘flipped’ methodology resulted in isolated and unequivocal detection of the NPS. Interestingly, the NPS signatures were consistent across all mixtures investigated and were 1712, 1000, and 777/1022 cm−1 for 5F‐PB‐22, phenibut, and N‐Me‐2‐AI containing samples, respectively. Thus indicating that the developed model systems could be applicable to structural analogs. NPS were detected to concentrations as low as 6.0% w/w. This flipped methodology was benchmarked to the instrument's output algorithms and outperformed these in terms of NPS detection, particularly for low concentration ternary and quinary mixtures. As a result, this study represents a critical change in the conceptualization of novel approaches for the detection of psychoactive substances and further denotes a blueprint for the development of detection methodologies of target analytes in complex mixtures. A novel approach for the in‐field detection of psychoactive substances in complex mixtures is reported, exploiting both Raman spectroscopy and computational approaches. In all cases, the target analyte was identified in the simulated street samples which denotes a significant superior performance to current in‐built algorithm in commercially available instrumentation.