Issues in Methodology and Applications for Therapeutic Drug Monitoring of Fluoxetine and Norfluoxetine Enantiomers

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Abstract
A standardization of the analytical procedures for monitoring of fluoxetine and norfluoxetine enantiomers is described. Simultaneous determination of fluoxetine and norfluoxetine enantiomers in plasma and serum was performed by high-performance liquid chromatography with a chiral stationary phase, using ultraviolet absorbance detection. The analytes were extracted from the biologic matrix by alkalinization with NaOH and solid-phase extraction. Stability studies were conducted in EDTA, lithium-heparinized plasma and in serum spiked with the analytes stored at+4°C for 1 week and at -20°C for 1 month. Furthermore, stability studies in NaOH and in the extraction solvents were executed. Using this methodology, EDTA plasma is the most suitable matrix for drug monitoring, even if the storage should not exceed 3 weeks at -20°C. Furthermore, the biologic sample should be left in NaOH for a short time before solid-phase extraction to prevent a degradation of matrix, which would interfere with the chromatographic analysis.