A Semi‐quantitative method for the detection of fentanyl using surface‐enhanced Raman scattering (SERS) with a handheld Raman instrument

Abstract

A handheld, spatially offset Raman spectroscopy (SORS) system was successfully used to obtain Surface‐enhanced Raman Scattering (SERS) spectra of fentanyl under simulated field conditions. A series of aqueous fentanyl solutions were prepared with commercially available gold nanoparticle solution, at concentrations ranging from 0.003 to 1697 μM. These SERS spectra were then used to generate two concentration calibration models (via a plot of peak area (1026 cm−1) versus concentration, and quantitative spectral decomposition using partial least squares (PLS1)). For both models, the relationship followed Langmuir adsorption and became non‐linear at concentrations above ~0.2 μM, with a limit of detection (LOD) of approximately 3 nM. The same technique was successfully used to measure fentanyl in the presence of two common “cutting agents,” heroin and glucose, at 1% and 2% fentanyl proportions (w/w). Fentanyl detection was successfully achieved, but mixture interference from the cutting agents prevented a calibration model being generated. Four fentanyl analogues were also investigated—butyrylfentanyl, furanylfentanyl, acetylfentanyl, and ocfentanyl. A concentration calibration model for each species was successfully generated, but differentiation from fentanyl proved more challenging, although several potential diagnostic peaks were identified. These results identified a pathway forward in using handheld equipment for the reliable detection of ultra‐low concentrations of fentanyl and fentanyl analogues via SERS, even when mixed with diluents. However, quantitative detection is negatively impacted in the presence of heroin and glucose. This also provides a starting point for a SERS‐based spectral library of fentanyl analogues, in combination with a range of different diluents.

Fentanyl detection and quantification using portable Raman spectroscopy in community drug checking

“…[26] Inherent challenges are in achieving sufficient sensitivity for lowconcentration actives and mitigating fluorescence. Recent interest in using the same instrumentation for SERS provides the potential for ultra-trace detection that could be applied in the identification of fentanyl [27][28][29][30] and its analogues, such as carfentanil. [31] In the context of drug checking, developing protocols that can work directly with powdered samples and without any sample preparation is particularly useful.…”

Implementing an integrated multi‐technology platform for drug checking: Social, scientific, and technological considerations

“…Because traditional Raman spectroscopy is limited in achieving measurable signals for substances present in low concentrations, surfaceenhanced Raman scattering (SERS) is pursued to overcome this barrier with the goal of trace detection. [47][48][49][50] The same Raman spectrometer is used for the SERS experiments. Here the sample is dissolved in a solution of 50 nm diameter gold spheres (BBI Solutions) in methanol with the addition of magnesium sulfate (Sigma Aldrich) as an aggregating agent.…”

“…Because traditional Raman spectroscopy is limited in achieving measurable signals for substances present in low concentrations, surface‐enhanced Raman scattering (SERS) is pursued to overcome this barrier with the goal of trace detection 47–50 . The same Raman spectrometer is used for the SERS experiments.…”

“…Here the sample is dissolved in a solution of 50 nm diameter gold spheres (BBI Solutions) in methanol with the addition of magnesium sulfate (Sigma Aldrich) as an aggregating agent. The LOD for fentanyl in the prepared solution using SERS has previously been reported to be as low as 1 ng/ml in laboratory samples, 50 and approximately 25 μg/ml in street samples 31 . While both IR and Raman are limited by the availability of libraries, this is particularly true of SERS, as SERS spectra are often significantly different from the corresponding Raman spectra, even in the case of pure compounds.…”

Forensic Identification of Fentanyl and its Analogs by Electrochemical-Surface Enhanced Raman Spectroscopy (EC-SERS) for the Screening of Seized Drugs of Abuse

“…The use of SERS for analyzing drug analytes has become quite popular. In fact, the investigation of many drugs of abuse has been explored with SERS including amphetamines, MDMA, and amphetamine-like substances (Bell et al, 2000;Sägmüller et al, 2001;Faulds et al, 2002); barbiturates (Farquharson and Lee, 2000); mephedrone (Mabbott et al, 2013); and other types of drugs including cocaine, morphine, hydrocodone, fentanyl, codeine, diazepam, and fentanyl analogs (Farquharson et al, 2011;Rana et al, 2011;Leonard et al, 2017;Haddad et al, 2018;Shende et al, 2019b;Wang et al, 2019, Smith et al, 2021Wang H. et al, 2021;Wang L. et al, 2021;Wilson et al, 2021;Zhang et al, 2021). The use of SERS has also enabled the analysis of these drug analytes in toxicological specimens such as urine, saliva, and blood (Inscore et al, 2011;Andreou et al, 2013;D'Elia et al, 2018;Shende et al, 2019a;Sivashanmugan et al, 2019;Han et al, 2021).…”