The Detection of 27 Fentanyl Compounds in Solid and Liquid Drugs Based on Differential Raman Spectroscopy

Fentanyl and its derivatives have been mainstays for the treatment of pain for many years. To accurately detect them in medical applications and customs, a rapid, sensitive, and selective method is urgently needed. In this study, we established a point-of-care-testing (POCT) differential Raman approach for the detection of fentanyl substances in liquid and solid conditions. The silver nanoparticle was prepared and characterized as SERS substrate, which can adsorb fentanyl-related molecules on the rough surface to enhance the Raman signal. Subsequently, 27 kinds of fentanyl-related substances were detected to determine that the POCT spectral resolution is better than 6 cm−1, Raman detection range is 100–3200 cm−1, and the detection limit of the fentanyl-related substances at 1002 cm−1 is 0.1–25 ppb. Furthermore, the Raman characteristic peaks of fentanyl were checked through comparison between theoretical calculations and experiments to obtain a database for rapid on-site inspection. Thus, the fast, accurate, stable POCT approach can be widely applied to monitor drugs and toxins due to its sensitivity, specificity, and abundance database.