A Critical Overview of Enzyme-Based Electrochemical Biosensors for L-Dopa Detection in Biological Samples

L-Dopa is an intermediate amino acid in the biosynthesis of endogenous catecholamines, such as dopamine. It is currently considered to be the optimal dopaminergic treatment for Parkinson’s disease, a neurodegenerative disorder affecting around 1% of the population. In an advanced stage of the disease, complications such as dyskinesia and psychosis are caused by fluctuations in plasma drug levels. Real-time monitoring of L-Dopa levels would be advantageous for properly adjusting drug dosing, thus improving therapeutic efficacy. Electrochemical methods have advantages such as easyto- use instrumentation, fast response time, and high sensitivity, and are suitable for miniaturization, enabling the fabrication of implantable or wearable devices. This review reports on research papers of the past 20 years (2003–2023) dealing with enzyme-based biosensors for the electrochemical detection of L-Dopa in biological samples. Specifically, amperometric and voltammetric biosensors, whose output signal is a measurable current, are discussed. The approach adopted includes an initial study of the steps required to assemble the devices, i.e., electrode modification and enzyme immobilization. Then, all issues related to their analytical performance in terms of sensitivity, selectivity, and capability to analyze real samples are critically discussed. The paper aims to provide an assessment of recent developments while highlighting limitations such as poor selectivity and long-term stability, and the laborious and time-consuming fabrication protocol that needs to be addressed from the perspective of the integrated clinical management of Parkinson’s disease.