Application of 5-HT-SO4 in Biomarker Research

A serotonin catabolite, serotonin O‐sulphate (5‐HT‐SO4), is hypothesised to accentuate the intensity of serotonin metabolism in the central nervous system (CNS). We hypothesised that serotonin O‐sulphate could be quantified in human plasma using modern liquid chromatography‐mass spectrometry. To test our hypothesis, we performed a critical literature review and a three‐stage trial. First, a suitable liquid chromatography‐mass spectrometry (LC‐MS/MS) method for detection of 5‐HT‐SO4 in human plasma samples was developed. Second, a pilot phase involving four healthy volunteers was executed. Finally, nine healthy volunteers were selected for the main study, where a basal plasma level of
5‐HT‐SO4 was measured before and after serotonergic stimulation of the central nervous system. One h after stimulation, six study subjects showed a decrease in 5‐HT‐SO4 levels, while three subjects showed an increase. This was the first study in which naturally occurring 5‐HT‐SO4 was detected by liquid chromatography–mass spectrometry (LC‐MS/MS) in the samples of human plasma obtained from healthy volunteers. The method developed was specific to the measurement of 5‐HT‐SO4 and opens up new possibilities to evaluate minor pathways or serotonin metabolism by minimally invasive methods.