Determination of fluoxetine and its metabolite norfluoxetine in human liver microsomes by reversed-phase HPLC in vitro

Acta Pharmacol Sin. 2000 Nov;21(11):1027-30.

Abstract

Aim: A high-performance liquid chromatography (HPLC) method was developed for the determination of fluoxetine (FLU) and its metabolite norfluoxetine (N-FLU) in human liver microsomes in vitro.

Methods: An incubation buffer containing human liver microsomes, NADPH-generating system, and FLU, after termination of enzyme reaction and addition of nortriptyline (NOR) as internal standard (IS), was extracted with n-hexane/acetonitrile, and separated on a reversed-phase ODS column. Detection was achieved at 226 nm by ultraviolet detector (UV).

Results: The limit of detection was 5 micrograms/L for both FLU and N-FLU. No potential interference was found. The method provides recoveries of up to 94%-104% and acceptable coefficients of variation were found for both within-run (< 7.8%) and day to day (< 9.1%) assays.

Conclusion: This method is rapid, sensitive, and simple for studying the metabolism of FLU and N-FLU.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid / methods
  • Fluoxetine / analogs & derivatives
  • Fluoxetine / analysis*
  • Fluoxetine / metabolism
  • Humans
  • In Vitro Techniques
  • Microsomes, Liver / chemistry*
  • Microsomes, Liver / metabolism

Substances

  • Fluoxetine
  • norfluoxetine