Strategies for the electrochemical determination of drugs in biofluids: The role of sample preparation in sensitivity and selectivity enhancement

The presence of drugs in different matrices is a growing concern that must be addressed to ensure prompt and accurate responses. They constitute a heterogeneous group of compounds and their low concentrations, as well as the potential presence of metabolites, make analytical determination more complex. In this context, sample preparation is a valuable tool for achieving the sensitivity and selectivity required for drug determination. This review discusses the role of this analytical process in combination with electrochemical detection for determining drugs in biofluids, compiling the scarce early examples that emerged before 2020 and critically evaluating the advances reported until 2025. The modification of electrodes and the introduction of extraction techniques have been critically discussed. Integrating sample preparation with electrochemical detection is identified as one of the most powerful approaches. • The electrochemical determination of drugs in biofluids is reviewed. • Electrodes can be modified to improve the electrochemical detection. • Sample preparation plays a key role in sensitivity and selectivity enhancement. • Sample preparation can be integrated with electrochemical detection for simplicity.