A new HPLC technique for the analysis of picomolar amounts of serotonin (5HT) in plasma and cerebrospinal fluid (CSF) is described. Bufotenin is used as internal standard. Detection is achieved electrochemically or fluorimetrically. The detection limit can be estimated as 50 pg 5HT/mL of either fluid (0.3 picomolar). The method is used to characterize a non-particulate pool of 5HT which is clearly distinct of the platelet pool. Administration of parachlorophenylalanine (PCPA) 300 mg/kg to rats leads to a 90% reduction in the plasmatic pool whereas platelet 5HT is only slightly decreased (3rd day after PCPA) or even increased (7th day after PCPA). Human concentration (n = 15) of 5HT in plasma is 2.6 +/- 0.9 ng/mL (X +/- S.D.). The application of the method to CSF of neurological patients reveals 5HT concentrations ranging from 93 to 962 pg/mL.
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