DETERMINATION OF FLUOXETINE AND ITS METABOLITE NORFLUOXETINE IN SERUMAND BRAIN-AREAS USING HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY WITH ULTRAVIOLET DETECTION

A high-performance liquid chromatography (HPLC) method using only 0.1 ml of serum or homogenate from brain areas has been developed for the determination of fluoxetine (FLU) and its metabolite, norfluoxetine (N -FLU), with ultraviolet detection at 227 nm. The small volume of sampl e required in this method allows studies n small animals, such as mous e. The method provides recoveries of up to 90% for both compounds. Acc eptable coefficients of variation were found for both within-run and d ay-to-day assays. The limit of detection was 5.0 ng/ml. No interferenc es were found with tricyclic antidepressant drugs and benzodiazepines, which allows this method to be used in clinical studies. Pharmacokine tic parameters for the two compounds are reported in mouse serum, fron tal cortex and caudate nucleus. We also report the values of FLU and N -FLU in serum from humans who were treated once daily with 20 mg of FL U, obtained after 1, 14 and 28 days of treatment.