Detection of low‐level fentanyl concentrations in mixtures of cocaine, <scp>MDMA</scp>, methamphetamine, and caffeine via surface‐enhanced Raman spectroscopy

Surface-enhanced Raman spectroscopy (SERS) was utilized to measure low-level fentanyl concentrations mixed in common cutting agents, cocaine, 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine, and caffeine. Mixtures were prepared with a fentanyl concentration range of 0-339 μM. Data was initially analyzed by plotting the area of a diagnostic peak (1026 cm^-1) against concentration to generate a calibration model. This method was successful with fentanyl/MDMA samples (LOD 0.04 μM) but not for the other mixtures. A chemometric approach was then employed. The data was evaluated using principal component analysis (PCA), partial least squares (PLS1) regression, and linear discriminant analysis (LDA). The LDA model was used to classify samples into one of three designated concentration ranges, low = 0-0.4 mM, medium = 0.4-14 mM, or high >14 mM, with fentanyl concentrations correctly classified with greater than 85% accuracy. This model was then validated using a series of "blind" fentanyl mixtures and these unknown samples were assigned to the correct concentration range with an accuracy >95%. The PLS1 model failed to provide accurate quantitative assignments for the samples but did provide an accurate prediction for the presence or absence of fentanyl. The combination of the two models enabled accurate quantitative assignment of fentanyl in binary mixtures. This work establishes a proof of concept, indicating a larger sample size could generate a more accurate model. It demonstrates that samples, containing variable, low concentrations of fentanyl, can be accurately quantified, using SERS.