Specific method for determination of gefitinib in human plasma, mouse plasma and tissues using high performance liquid chromatography coupled to tandem mass spectrometry

Ming Zhao, Carol Hartke, Antonio Jimeno, Jing Li, Ping He, Yelena Zabelina, Manuel Hidalgo, Sharyn D. Baker

Research output: Contribution to journalArticlepeer-review

Abstract

A rapid, sensitive and specific method was developed and validated using liquid chromatography-tandem mass spectrometry (LC/MS/MS) for determination of gefitinib in human plasma and mouse plasma and tissue. Sample preparation involved a single protein precipitation step by the addition of 0.1 mL of plasma or a 200 mg/mL tissue homogenate diluted 1/10 in human plasma with 0.3 mL acetonitrile. Separation of the compounds of interest, including the internal standard (dS)-gefitinib, was achieved on a Waters X-Terra™ C18 (50 mm × 2.1 mm i.d., 3.5 μm) analytical column using a mobile phase consisting of acetonitrile-water (70:30, v/v) containing 0.1% formic acid and isocratic flow at 0.15 mL/min for 3 min. The analytes were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated over the range of 1-1000 ng/mL for the human plasma samples and 5-1000 ng/mL for mouse plasma and tissue samples with values for the coefficient of determination of >0.99. The values for both within- and between-day precision and accuracy were well within the generally accepted criteria for analytical methods (<15%). This method was subsequently used to measure concentrations of gefitinib in mice following administration of a single dose of 150 mg/kg intraperitoneally and in cancer patients receiving an oral daily dose of 250 mg.

Original languageEnglish (US)
Pages (from-to)73-80
Number of pages8
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume819
Issue number1
DOIs
StatePublished - May 5 2005

Keywords

  • Gefitinib
  • LC/MS/MS
  • Pharmacokinetics
  • ZD1839

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Fingerprint Dive into the research topics of 'Specific method for determination of gefitinib in human plasma, mouse plasma and tissues using high performance liquid chromatography coupled to tandem mass spectrometry'. Together they form a unique fingerprint.

Cite this