Radioimmunoassay for Psychotropic Drugs II: Synthesis and Properties of Haptens for Tricyclic Antidepressants

For the development of radioimmunoassay procedures for tricyclic antidepressants, two drug haptens were synthesized for each of the two amitriptyline-nortriptyline and imipramine-desipramine groups. In one case, nortriptyline or desipramine was treated with succinic anhydride to yield N -(3-carboxypropionyl) derivatives; in the other case, the haptens were novel, N -(2-carboxyethyl) derivatives. The hapten and its corresponding ester were characterized by GLC-mass spectrometry, PMR spectrometry, and IR spectrophotometry. Each hapten was coupled to bovine serum albumin, and the number of hapten residues per mole of bovine serum albumin was determined by UV spectrophotometric methods. Antibodies to each hapten protein conjugate were developed in rabbits, and titers of the antiserums were checked by evaluating their binding characteristics to tritiated drug.