Drug-Checking with Molecularly Imprinted Polymers: Addressing Xylazine-Contaminated Fentanyl.

Xylazine adulterated Fentanyl is considered one of the deadliest drug threats ever faced in the United States. However, due to the complexity of the illegal drug supply, xylazine detection in the frame of drug-checking (harm reduction) remains an unsolved challenge, one which has cost numerous lives across North America. In this work, we present two sensor platforms for detecting xylazine in drug-checking applications. Both platforms are based on molecularly imprinted polymers (MIPs) using vinyl phosphonic acid as the main monomer. By combining the MIPs with thermometric and colorimetric readouts, we achieved xylazine detection in a wide concentration range, relevant in real-world scenarios. First, the heat-transfer method (HTM) allowed xylazine detection in the low concentration range within 15 min per concentration, with a limit of detection (LoD) of 16.5 ng/mL (75 nM). Second, a dye displacement assay employing methylene blue provided rapid (<5 min), visible detection with an LoD > 76 μg/mL-five times lower than the average concentration reported for street samples. Additionally, the colorimetric sensor exhibited potential for detecting various unwanted xylazine analogues, which could potentially act as fentanyl adulterants in the future. Most importantly, the colorimetric sensor consistently detected xylazine in a highly complex, street-like fentanyl sample containing five common interferents. The synergy of the proposed sensors offers a promising alternative for centralized and on-site xylazine screening in harm reduction settings.