Quantification of Monoamine Neurotransmitter Metabolites and Cofactors in Cerebrospinal Fluid: State-of-the-Art

Inborn errors of monoamine neurotransmitter metabolism are rare diseases characterized by nonspecific neurological symptoms. These symptoms appear in early childhood and correspond to movement disorders, epilepsy, sleep disorders and/or mental disability. Cerebrospinal fluid biomarkers have been identified and validated to allow specific diagnosis of these diseases. Biomarkers of inborn errors of monoamine neurotransmitter metabolites are divided in two groups: monoamine neurotransmitter metabolites and pterins. Biomarkers quantification in cerebrospinal fluid is based on high-performance liquid chromatography separation coupled to electrochemical detection, fluorescence detection, or mass spectrometry. The following article reviews the advances in the proposed routine methods for the measurement of these analytes in cerebrospinal fluid. The purpose of this review is to compare the various proposed methods in terms of sample preparation, chromatographic conditions and detection modes. Despite the broad range of proposed methods, quantification of inborn errors of monoamine neurotransmitter biomarkers remains a great challenge, given the complexity of biological fluids and the low amounts of analytes that are present in cerebrospinal fluid.