Development of a rapid and sensitive LC-MS/MS assay for the determination of sorafenib in human plasma

Lokesh Jain, Erin R. Gardner, Jürgen Venitz, William Dahut, William D. Figg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

A rapid and sensitive liquid chromatography/tandem mass spectrometric (LC/MS/MS) assay was developed for the quantitative determination of sorafenib in human plasma. Sample pretreatment involved simple protein precipitation by the addition of 0.5 mL acetonitrile, containing internal standard ([2H3, 15N] sorafenib), to 50 μL of plasma sample volume. Separation was achieved on a Waters SymmetryShield RP8 (2.1 mm × 50 mm, 3.5 μm) column at room temperature using an isocratic elution method with acetonitrile/0.1% formic acid in water: 65/35 (v/v) at a flow rate of 0.25 mL/min. Detection was performed using electrospray ionization in positive ion multiple reaction monitoring (MRM) mode by monitoring the ion transitions from m/z 464.9 → 252.0 (sorafenib) and m/z 469.0 → 259.0 (internal standard). Calibration curves were linear in the concentration range of 5-2000 ng/mL. The accuracy and precision values, calculated from three different sets of quality control samples analyzed in quintuplicate on six different days, ranged from 92.86% to 99.88% and from 1.19% to 4.53%, respectively.

Original languageEnglish
Pages (from-to)362-367
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume46
Issue number2
DOIs
StatePublished - 22 Jan 2008
Externally publishedYes

Keywords

  • BAY43-9006
  • Kinase inhibitor

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