Enantiomeric separation of fluoxetine and norfluoxetine in plasma and serum samples with high detection sensitivity capillary electrophoresis

A capillary electrophoresis method was optimized for the stereoselective an alysis of the antidepressant drug fluoxetine and its main demethylated meta bolite norfluoxetine using a cyclodextrin-modified sodium phosphate buffer at pH 2.5. The combination of a neutral and a negatively charged cyclodextr in, dimethylated-beta- and phosphated-gamma-respectively, provided the base line enantiomeric separation of the two compounds. The very low concentrati ons of chiral selectors employed together with the use of a high sensitivit y detection cell of special design (zeta-shaped) in a diode array UV detect or allowed us to reach a limit of detection of 0.005 and 0.01 mu g/mL for f luoxetine and norfluoxetine, respectively. Analysis of fluoxetine and norfl uoxetine standard mixtures showed a reproducibility of migration times and peak area and linearity in the concentration range of 0.1-2.0 mu g/mL. The optimized method was applied to the analysis of clinical serum and plasma s amples of patients under depression therapy. In all the analyzed samples th e enantiomeric forms of fluoxetine and norfluoxetine were easily identified . The fluoxetine and metabolite enantiomeric ratio confirmed the stereosele ctivity of the metabolic process of the fluoxetine drug in accordance with the literature data.