Resolving Signal Overlap in Fentanyl and Cocaine Detection Using Dual-pH Differential Pulse Voltammetry in Illicit Drug Samples.

Fentanyl poses serious health risks to drug users due to its high potency and overdose potential. The widespread adulteration of fentanyl with cocaine (and vice versa) presents additional dangers, as their interactions may alter user experience and dosing, their co-occurrence may interfere with the accuracy of on-site drug-testing tools, and cocaine's stimulant effects can mask fentanyl-induced respiratory depression, misguiding harm-reduction decisions. Rapid, simultaneous detection of both drugs is essential for harm reduction and forensic use yet challenging due to overlapping electrochemical signals in neutral media. This study introduces an electrochemical sensing method using screen-printed electrodes (SPEs) and sodium dodecyl sulfate (SDS) to enhance detection via differential pulse voltammetry (DPV). A dual-pH strategy enables selective detection of fentanyl at pH 4.5 and simultaneous detection of both analytes at pH 10. Fentanyl concentration is quantified at pH 4.5 and subtracted from the total signal at pH 10 to determine cocaine concentration. The method achieved LODs of 2.67 μM (fentanyl, pH 4.5), 2.89 μM (fentanyl, pH 10), and 1.28 μM (cocaine, pH 10). Applied to street samples previously analyzed by GC-MS, the sensor demonstrated high sensitivity, selectivity, and reproducibility, enabling accurate determination of cocaine and semi-quantitative detection of fentanyl in complex mixtures and supporting its utility for rapid on-site drug screening.