Fluoxetine, a selective serotonin reuptake inhibitor, is a first-line drug in the treatment of depression, with fewer side effects and better tolerated by the patient.

Fluoxetine is a good candidate for therapeutic drug monitoring due to the fact that it has a very extensive pharmacokinetic interindividual variability and it is bio-transformed to a pharmacological active metabolite, norfluoxetine.

No data that provides a good correlation between fluoxetine and active metabolite levels and therapeutic effect exist. Still, plasma concentrations that correspond to therapeutic doses are found near the value of 0.4 μg/mL, requiring very sensitive methods.

Methods for fluoxetine determination most commonly found in literature are chromatographic methods (especially HPLC and GC) coupled with various detectors. In terms of equipment and costs, UV detection is the most accessible but it`s sensitivity and selectivity are greatly surpassed by fluorescence and mass spectrometry detection methods.

Plasma and urine are the most common samples used for drug determination, with liquid-liquid extraction or solid phase extraction as preparation methods, often using an internal standard.