Development and applications of novel strategies for the enhanced mass spectrometric quantification of biogenic amines

Liquid chromatography in combination with triple-quadrupole mass spectrometry (LC-MS/MS) is rapidly developing as the analytical technique of choice for quantitative analysis of small molecules such as steroid hormones, vitamins, and biogenic amines. In recent years, there has been a shift towards widespread adaption of LC-MS/MS in the field of laboratory medicine. One of the compound classes that remains difficult to analyze especially in plasma, are the biogenic amines. Biogenic amines are biologically active compounds containing one or more amine groups and are produced from amino acids. Dopamine, norepinephrine, and epinephrine are synthesized from tyrosine; serotonin from tryptophan, and histamine from histidine. They are regarded as the “classic” biogenic amines, and foremost known for their roles as neurotransmitter. Biogenic amines are important markers for the diagnosis of neuroendocrine neoplasia. Neuroendocrine tumors are rare tumors that originate from cells of the endocrine and nervous system. One common characteristic of neuroendocrine tumors is that they have the ability to take up and metabolize amine precursors. Excessive production of biogenic amines may result in endocrine related complaints. No methods were available that enable the simultaneous profiling of all potentially relevant biogenic amine markers in one profile. We developed new approaches allowing simultaneous detection of these amines, their precursors, and metabolites that are of great interest. They could potentially aid in the diagnosis and management of neuroendocrine tumors. The aim of this thesis was to investigate and develop novel approaches for the enhanced mass spectrometric detection of neuroendocrine biomarkers.