Rapid and Direct Detection of Methamphetamine in Biofluids using a MXene‐Enabled Electrochemical Sensor

ABSTRACT Illicit drug abuse presents a global challenge to public health and security, creating an urgent need for reliable detection methods to curb trafficking and mitigate societal harm. Methamphetamine (METH), a highly addictive and widely circulated stimulant, requires urgent monitoring solutions. We introduce an approach for the rapid and direct detection of METH using an electrochemical sensor enhanced with MXene nano‐interfaces that operates on the principle of electrochemical oxidation. Theoretical simulations are conducted to elucidate the reaction pathway of METH and to analyze the molecular interactions between METH and the MXene surface, providing key insights into the underlying molecular dynamics. The rich surface functionalities of MXene enable a favorable structural affinity with METH, facilitating enhanced interfacial interactions that promote oxidation kinetics and amplify electrochemical responses. The sensor demonstrates a linear response to METH across a concentration range from 2 ngmL ⁻¹ to 50 µg mL ⁻¹ , alongside satisfactory anti‐interference performance and repeatability, rendering it appropriate for on‐site preliminary screening of positive samples. Its successful validation in complex biological matrices confirms its broad applicability. By combining user‐friendly operation with a rapid response, this method establishes a robust theoretical framework and a practical solution for the on‐site screening of METH and related illicit substances.