Synthesis and properties of haptens for the development of radioimmunoassays for thioridazine, mesoridazine, and sulforidazine.

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[1-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten-protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.

GLC analysis of thioridazine, mesoridazine, and their metabolites.

A GLC method for measuring thioridazine, mesoridazine, their metabolites, and possibly other phenothiazines was developed. By using this method, seven different phenothiazine derivatives, thioridazine, and six known thioridazine metabolites were extracted and separated. This method was tested by assaying plasma samples from 30 hospitalized psychiatric patients receiving thioridazine or mesoridazine.