Determination of fluoxetine and its metabolite norfluoxetine in serum and brain areas using high-performance liquid chromatography with ultraviolet detection

J Chromatogr B Biomed Sci Appl. 1998 Apr 10;707(1-2):175-80. doi: 10.1016/s0378-4347(97)00588-4.


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 sample required in this method allows studies in small animals, such as mouse. The method provides recoveries of up to 90% for both compounds. Acceptable coefficients of variation were found for both within-run and day-to-day assays. The limit of detection was 5.0 ng/ml. No interferences were found with tricyclic antidepressant drugs and benzodiazepines, which allows this method to be used in clinical studies, Pharmacokinetic parameters for the two compounds are reported in mouse serum, frontal 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 FLU, obtained after 1, 14 and 28 days of treatment.

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / analysis*
  • Antidepressive Agents, Second-Generation / blood
  • Antidepressive Agents, Second-Generation / pharmacokinetics
  • Brain Chemistry*
  • Calibration
  • Caudate Nucleus / chemistry
  • Chromatography, High Pressure Liquid
  • Fluoxetine / analogs & derivatives
  • Fluoxetine / analysis*
  • Fluoxetine / blood
  • Fluoxetine / pharmacokinetics
  • Mice
  • Prefrontal Cortex / chemistry
  • Reference Standards
  • Reproducibility of Results
  • Spectrophotometry, Ultraviolet


  • Antidepressive Agents, Second-Generation
  • Fluoxetine
  • norfluoxetine