The measurement of platelet-poor plasma serotonin: a systematic review of prior reports and recommendations for improved analysis.

BACKGROUND Recent reports of new and important roles for serotonin (5-hydroxytryptamine, 5-HT) in the periphery have substantially increased interest in measuring peripheral serotonin. Nearly all circulating serotonin is found within platelets and this pool has been assessed by measuring serotonin in whole blood or in platelet-rich plasma. Measurement of the much smaller but potentially critically important pool of human free plasma serotonin in platelet-poor plasma (PPP) has proven much more difficult, with a wide range of reference values reported. CONTENT To characterize the available data we carried out a systematic literature search of previous reports of PPP serotonin and attempted to determine the best estimate of true PPP serotonin concentration in humans. A total of 101 published reports that included PPP serotonin values in healthy controls were found and included in the summary statistical analyses. The distribution of PPP serotonin values demonstrated high skewness (+1.98), and the reported values ranged from 0.6 to 179 nmol/L, with a mean of 31.6 nmol/L, an SD of 38.9 nmol/L, and a median of 14.8 nmol/L. SUMMARY Reported concentrations for human PPP or free plasma serotonin were highly discrepant, with most reports giving erroneously high values that should be disregarded. Inherent difficulties in selectively measuring the extremely low concentrations of serotonin present in PPP and in preparing PPP without contamination from platelet-derived serotonin contributed to the problem, as did the failure of researchers to compare their results with those from prior studies. There is a clear and pressing need for reference materials for the measurement of plasma (PPP) serotonin.