Quantitative electrochemical analysis of serotonin

Abstract

Serotonin (5-hydroxytryptamine, 5-HT) is a key neurotransmitter that plays a central role in the regulation of mood, cognition, gastrointestinal function, and immune responses. In humans, the majority of serotonin is found in the gastrointestinal system, with smaller amounts in blood platelets and the brain. Because serotonin levels are dynamically controlled through tightly regulated processes of synthesis, release, reuptake, and metabolism, measuring them accurately in real time is challenging. Disturbance in serotonin signaling can lead to brain disorders such as Parkinson’s disease, depression, anxiety, and gastrointestinal conditions, which denotes the importance of developing reliable methods capable of accurately detecting serotonin concentration, especially in the brain.

Serotonin from urine and blood samples is typically measured using high-performance liquid chromatography (HPLC) coupled with mass spectrometry, fluorometric detection, or enzyme linked immunosorbent assay (ELISA), which offer high sensitivity and selectivity but are unsuitable for real-time measurements. In vivo brain measurements of serotonin are particularly demanding. Traditional approaches using microdialysis combined with HPLC provide sensitive analysis of extracellular fluid but are invasive and offer limited temporal resolution. To address these limitations, voltammetric techniques such as fast-scan cyclic voltammetry and related methods have been developed, enabling real-time, high-resolution monitoring with reduced tissue damage and providing insight into serotonin oxidation mechanisms.

The purpose of this thesis was to evaluate the performance of voltammetric techniques for serotonin detection and to analyze how key electrochemical parameters—particularly scan rate, and potential waveform—influence the oxidation mechanism and voltammetric response of serotonin. In addition, the effects of electrode material selection, surface modification, and electrode fouling on sensitivity, stability, and reliability were critically examined and compared with other available analytical methods.

However, voltammetric detection of serotonin is constrained by challenges related to sensitivity, selectivity, and especially electrode fouling. Oxidation by-products can accumulate at the electrode surface, causing signal degradation and poor reproducibility. Although strategies such as waveform optimization, fast-scan techniques, and surface modifications have been proposed to mitigate fouling effects, long-term stability remains difficult to achieve. This work highlights both the advantages and the remaining limitations of voltammetric methods in comparison with chromatographic and spectroscopic approaches.

In conclusion, this thesis suggests that voltammetric techniques have significant potential for quantitative and dynamic serotonin analysis, particularly in neuroscience research. Nevertheless, challenges related to selectivity, calibration, and electrode fouling currently limit their broader applicability. Further developments in electrode materials, surface engineering, and optimized measurement protocols are required to improve the reliability and reproducibility of electrochemical serotonin monitoring in biological and clinical applications.