Abstract
A method has been developed for the enantioselective determination of the title compound S-145, a novel thromboxane A2 receptor antagonist, in a plasma by competitive radioimmunoassay. In order to obtain an antiserum that is optically specific to (+)-S-145 or (-)-S-145, hapten-carrier conjugates were individually prepared by coupling with bovine serum albumin. In displacement studies with enantiomerically pure radioligands, the opposite enantiomer showed a negligible cross-reaction (0.1 to 0.3%) and the racemate showed about a 50% cross-reaction. No cross- reactivity was found with related prostanoids, except for a few metabolites of S-145. The minimum detectable dose (p<0.05) of radioimmunoassays for each enantiomer of 5-145 was 0.5pg/tube. By applying these radioimmunoassays to plasma samples, we developed a precise assay technique without using prior extraction. The limit of the determination of both enantiomers was 200pg/ml in human plasma. The recovery was almost 100%. The intra- and inter-assay variances were 6-12% and 4-10% for human plasma, respectively. When the plasma levels were determined for each enantiomer after an oral administration of the S-145 racemate to several animal species, significant differences were observed between the two enantiomers.
