Sensitive assay for the tricyclic antidepressant Ro 11-2465 in biological fluids by high-performance liquid...

A high-performance liquid chromatographic assay, suitable for pharmacokinetic studies, has been developed for the new tricyclic antidepressant Ro 11-2465, at present under clinical investigation. For concentrations above 0.5 ng/ml, the method involves a simple extraction at basic pH with an organic solvent followed by direct chromatography of this extract on a silica gel column using fluorescence detection. For concentrations below 0.5 ng/ml, an extensive clean-up procedure is required. In both procedures, however, evaporation of the extract and reconstitution of the residue is avoided. The detection limit, using 1 ml of plasma, is about 0.1 ng/ml. This sensitivity is sufficient for following single-dose kinetics of Ro 11-2465 in man.