Determination of atomoxetine and its metabolites in conventional and non-conventional biological matrices by liquid chromatography-tandem mass spectrometry

Emilia Marchei, Esther Papaseit, Oscar Q. Garcia-Algar, Magi Farrè, Roberta Pacifici, Simona Pichini

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17 Citations (Scopus)

Abstract

A procedure based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) is described for determination of atomoxetine (ATX) and its metabolites 4-hydroxyatomoxetine (4-OH-ATX) and N-des-methylatomoxetine (N-des-ATX) in plasma, urine, oral fluid and sweat using duloxetine as internal standard. Analytes were extracted from 0.5mL biological fluids and sweat patch with 2mL aliquots of tert-butyl methyl ether. The organic layer was evaporated and redissolved in mobile phase. Chromatographic separation was carried out on reverse-phase column and an isocratic mobile phase formed by 40% water and 60% 5mM ammonium acetate, 47.2mM formic acid, 4mM trifluoroacetic acid in acetonitrile-water (85:15, v/v) at a flow rate of 0.5mL/min. Separated analytes were identified and quantified by positive electrospray ionization tandem mass spectrometry and in multiple reaction monitoring acquisition mode. Limits of quantifications for the three analytes were 0.5ng/mL plasma and oral fluid, 10ng/mL urine and 1ng/patch using 0.5mL biological fluids or one sweat-patch per assay. Calibration curves were linear over the calibration ranges with r 2>0.99. At three concentrations spanning the linear dynamic range of the assay, mean recoveries in different biological matrices were always higher than 65%. This method was applied to therapeutic monitoring of ATX and its metabolites 4-OH-ATX and N-des-ATX in conventional and non-conventional biological matrices from individuals in drug treatment. © 2011 Elsevier B.V.
Original languageEnglish
Pages (from-to)26-31
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume60
DOIs
Publication statusPublished - 23 Feb 2012

Keywords

  • Atomoxetine
  • Oral fluid
  • Plasma
  • Sweat
  • Tandem mass spectrometry

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