Development of a radioimmunoassay procedure for mesoridazine and its comparison with a high-performance liquid...

A radioimmunoassay (RIA) procedure for mesoridazine was developed using an antiserum raised in rabbits immunized with N-(2-carboxyethyl) desmethylmesoridazine-porcine thyroglobulin conjugate. The RIA procedure enabled the quantitation of 40 pg of mesoridazine in a 200-microliters human plasma sample with a coefficient of variation of less than 5%. Except for N-desmethylmesoridazine, the antiserum showed no marked cross-reaction with any of the other available potential cross-reactants. Furthermore, statistically indistinguishable results were obtained for the determination of mesoridazine in the presence or absence of a fivefold excess of thioridazine or sulforidazine. This RIA procedure was compared with a high-performance liquid chromatographic (HPLC) method by determining concentrations of mesoridazine in plasma samples from human volunteers over 72 h after administration of single 50-mg oral doses of thioridazine hydrochloride. Good correlation existed between the assay values (n = 55) determined by the RIA and HPLC methods (r2 = 0.940), but the slope of the regression line was significantly different from 1.0 (p less than 0.05, when RIA values were plotted on the gamma axis and HPLC values were plotted on the chi axis; p less than 0.001, when HPLC values were plotted on the gamma axis and RIA values were plotted on the chi axis). The plot of the differences between these two assay values against the average of the assay values showed, however, that the differences were independent of the concentration range studied. Moreover, statistically favorable comparisons were obtained for area under the plasma level/time curve to 48 h (AUC0(48)), Cmax, and Tmax calculated from the data obtained by the two methods.