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Quantitative Determination of Amitriptyline and Its Metabolite in Rat Plasma by Liquid Chromatography-tandem Mass Spectrometry

  • Chae, Jung-Woo (College of Pharmacy, Chungnam National University) ;
  • Baek, In-Hwan (Incrementally Modified Drug (IMD), Yuhan Research Institute) ;
  • An, Jung-Hwa (College of Pharmacy, Chungnam National University) ;
  • Kim, Eun-Jung (Division of Pharmacological Research, National Institute of Food and Drug Evaluation, Korea Food & Drug Evaluation) ;
  • Kwon, Kwang-Il (College of Pharmacy, Chungnam National University)
  • Received : 2012.02.21
  • Accepted : 2012.03.26
  • Published : 2012.07.20

Abstract

A rapid, specific, and reliable LC-MS/MS-based bioanalytical method was developed and validated in rat plasma for the simultaneous quantitation of amitriptyline and its metabolite nortriptyline. Chromatographic separation of these analytes was achieved on a Gemini C18 column ($50{\times}4.60mm$, $5{\mu}m$) using reversed-phase chromatography. The mobile phase was an isocratic solvent system consisting of 1% formic acid in water and methanol (10:90, v/v), at a flow rate of 0.2 mL/min. The analytical range was set as 0.1-500 ng/mL for amitriptyline and 0.08-500 ng/mL for nortriptyline using a $200{\mu}L$ plasma sample. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. The validated method was successfully applied to a pharmacokinetic study in six rats after oral administration of amitriptyline (15 mg/kg). This method allows laboratory scientists to rapidly determine amitriptyline and nortriptyline concentrations in plasma.

Keywords

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