Capillary Electrophoresis With Amperometric Detection for Neurotransmitter Analysis: Principles, Electrode Materials, Methodologies, and Applications

Capillary electrophoresis with amperometric detection has become a powerful tool for the determination of electroactive neurotransmitters due to its high separation efficiency, minimal sample consumption, and excellent detection sensitivity. This review provides the first comprehensive summary specifically on monoamine neurotransmitters and related compounds in biological systems. Fundamental principles of amperometric detection, electrode positioning strategies, and approaches to high-voltage decoupling are described, followed by a critical comparison of electrode materials including carbon fiber, glassy carbon, graphite, noble metals, boron-doped diamond, and chemically modified or multielectrode designs. Their impact on noise, sensitivity, fouling resistance, and ease of integration is highlighted. Particular attention is given to background electrolyte composition, where phosphate buffers are most widely used, while 2-(N-morpholino)ethanesulfonic acid systems have enabled the lowest limits of detection, often reaching the attomole range. Applications span human urine, blood, lymphocytes, brain tissue, microdialysates, invertebrate tissues, and single cells, demonstrating capillary electrophoresis with amperometric detection as a versatile platform for neurochemical analysis. Advances in online preconcentration, dynamic pH junctions, and redox-cycling electrodes have further improved selectivity and sensitivity. Finally, current limitations, such as electrode fouling and interface robustness, are discussed together with emerging trends, including clinical translation and in vivo neuroanalysis.