The serotonin-O-sulfate as a potential plasma surrogate biomarker

According to the latest European regulatory policy a close attention is paid to research into the use of biomarkers and surrogate markers in the development of pharmaceuticals. Since early sixties of the last century when a sulphation of serotonin was described from which the biotransformation product serotonin-O-sulfate (5-HT-SO4) was formed, is assumed it accentuates the intensity of serotonin metabolism in the central nervous system. Not so many researches are done with this compound particularly in humans, but taking into account serotonin-o-sulfate is able to reflect serotonin pathways it has a potential to be employed as a surrogate biomarker to follow the effects of a specific serotonergic treatment. Hereby we summarize the literature evidence of 5-HT-SO4 appearance in vivo. So far this indolemine was found in animal neurons, endothelial cells, urine and the only site of detection in humans was cerebrospinal liquid. Probably due to its absence in the easy accessible body fluids the clinical significance of 5-HT-SO4 has thus far been lessened. In result of our latest research we developed a suitable liquid chromatography–mass spectrometry (LC-MS) method, found this neurotransmitter degradation product in the human plasma and performed the first in humans clinical trial detecting it in healthy volunteers. According to the earlier animal research it is hypothised that 5-HT-SO4 release is site specific and emphasizes central nervous system specific serotonin metabolism, therefore a further research is necessary to define the origin of plasmatic 5-HT-SO4 in humans.