Radioimmunoassay for the sulfoxide metabolite of trifluoperazine and its application to a kinetic study in humans.

Antibodies were produced in rabbits immunized with 10-[[3-[4-(2-carboxyethyl)-1-piperazinyl]-propyl]]-2 -trifluoromethyl-10H-phenothiazine sulfoxide-bovine serum albumin conjugate. The subsequently developed radioimmunoassay (RIA) procedure enables, for the first time, the quantitation of the sulfoxide metabolite of trifluoperazine in the plasma of humans after administration of therapeutic doses of trifluoperazine, in which 60 pg of the sulfoxide metabolite in 200 microL of plasma can be measured with a CV of less than 3%. Similar results were obtained by this assay with or without a benzene extraction step and also in the presence or absence of a large excess of trifluoperazine and suspected major metabolites of trifluoperazine. This RIA procedure, together with a previously developed RIA for trifluoperazine was used to directly determine plasma concentrations of trifluoperazine and its sulfoxide metabolite after administration of a single, low, oral dose of trifluoperazine to five healthy volunteers. The rapidly appearing, relatively high concentrations of the sulfoxide metabolite are indicative of presystemic sulfoxidation. The mean plasma elimination half-life for the sulfoxide metabolic of trifluoperazine was 5.8 +/- 1.3 h.