Liquid chromatography-tandem mass spectrometric assay for the quantitative determination of the tyrosine kinase inhibitor quizartinib in mouse plasma using salting-out liquid-liquid extraction

  • Irene A Retmana
  • , Jing Wang
  • , Alfred H Schinkel
  • , Jan H M Schellens
  • , Jos H Beijnen
  • , Rolf W Sparidans

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

A bioanalytical assay for quizartinib -a potent, and selective FLT3 tyrosine kinase inhibitor- in mouse plasma was developed and validated. Salting-out assisted liquid-liquid extraction (SALLE), using acetonitrile and magnesium sulfate, was selected as sample pretreatment with deuterated quizartinib as internal standard. Separation was performed with reversed-phase liquid chromatography followed by detection with positive electrospray-triple quadrupole mass spectrometry in the selected reaction monitoring mode. The assay was successfully validated for mouse plasma in a 2-2000ng/ml calibration range with r(2)=0.9958±0.0028 (n=7) for linear regression with the inverse square of the concentration as a weighting factor. The within-run precision (n=18), between-run precision and accuracy were 2.9-6.0%, 4.5-8.9% and 91.7-109.4% respectively. The drug was stable under all relevant conditions. Finally, the assay was successfully applied in a pharmacokinetic pilot study in plasma of FVB/NRj mice treated with quizartinb orally.

Original languageEnglish
Pages (from-to)300-305
Number of pages6
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1061-1062
DOIs
Publication statusPublished - 1 Sept 2017

Keywords

  • Animals
  • Benzothiazoles
  • Chromatography, Liquid
  • Female
  • Linear Models
  • Mice
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Reproducibility of Results
  • Tandem Mass Spectrometry

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