Neurotransmitter analysis using liquid chromatography-electrochemical detection in the 21st century: Critical review from an analytical chemistry perspective

Neurotransmitter research (detection, identification, determination) plays a special role in neuroscience, neurochemical research, and biomedical analyses. Their type or quantity allows for a better understanding of brain function, diagnosis of neurological diseases, monitoring the effects of neuroactive substances, assessing treatment effectiveness, or conducting scientific research. For these reasons, it is essential to use analytical methods suitable to detect neurotransmitters at low levels, most often in biological samples with a complex matrix (e.g., tissue homogenates, cerebrospinal fluid). This review article focuses on the use of high-performance liquid chromatography with electrochemical detection for the detection and determination of neurotransmitters as an alternative technique to mass spectrometry, capillary electrophoresis, electrochemical methods, or biosensors. The achievements made in the 21st century are presented with particular emphasis on the point of view of analytical chemistry (highly sensitive, precise, versatile applications, low‑cost/economy, multi-analyte). The article presents and discusses the description of chromatographic methods, analytical procedure validation, and the most important validation parameters, categorized into three groups: monoamines and their metabolites, amino acids, and acetylcholine with choline. Additionally, the scope and purpose of the research conducted in the area of neurotransmitter determination, the description of the tested biological samples, the method of their preparation, and the extraction procedure are presented. A novelty is the use of a generalized evaluation of chromatographic methods using tools such as RGB Additive Color Model for Analytical Method Evaluation, and Blue applicability grade index for the evaluation of method practicality. The motivation for using this technique and future perspectives are briefly discussed.