A validated microfluidics-based LC-chip-MS/MS method for the quantitation of fluoxetine and norfluoxetine in rat serum

Virginie Houbart, Anne-Catherine Servais, Thierry D. Charlier, Jodi L. Pawluski, Frederic Abts, Marianne Fillet*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Web of Science)

Abstract

An increasing number of quantitative bioanalyses need to be performed on samples available in limited volumes, such as pharmacokinetic studies on small animals. In this context, microfluidic systems as the LC-chip device coupled to a mass spectrometer combine small sample volume requirements and high sensitivity. In this study, we present the development of a microfluidics-based method for fluoxetine (FLX) and norfluoxetine (NFL) quantitation dedicated to pharmacokinetic investigations in the rat serum. Using the methodology of experimental design, LC parameters were optimised in terms of peak resolution, analysis time, and sensitivity. An SPE method was then developed for serum samples on miniaturised 96-well plates containing a mixed-mode strong cation exchanger that provided very clean extracts with good analyte recovery (>= 66.0%). The total SPE-LC-MS/MS process required only 20 mu L per sample and the method provided a good sensitivity in a total run time of 12 min. Finally, the developed method for FLX and NFL quantitation in rat serum was fully validated. After having selected the most appropriate regression model on the basis of the accuracy profiles, method selectivity, trueness, precision, accuracy and linearity were demonstrated.
Original languageEnglish
Pages (from-to)3370-3379
JournalElectrophoresis
Volume33
Issue number22
DOIs
Publication statusPublished - Nov 2012

Keywords

  • Fluoxetine
  • Mass spectrometry
  • Microfluidics
  • Pharmacokinetic study

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