Determination of cediranib in mouse plasma and brain tissue using high-performance liquid chromatography–mass spectrometry

A new high performance liquid chromatography coupled with tandem mass spectrometry (HPLC–MS/MS) assay for cediranib, a tyrosine kinase inhibitor for VEGFRs, was developed and validated, for the determination of plasma and brain levels of cediranib in small specimen volumes. Tyrphostin (AG1478) was used as internal standard. Mouse plasma and brain homogenate samples were prepared using liquid–liquid extraction. The assay was validated for a 2.5–2500 ng/mL concentration range for plasma, and for 1–2000 ng/mL range for brain homogenate. For these calibration ranges, within-assay variabilities were 1.1–14.3% for plasma and 1.5–9.4% for brain homogenate; between-assay variabilities were 2.4–9.2% for plasma, and 4.9–10.2% for brain homogenate. Overall accuracy ranged from 101.5 to 107.0% for plasma and 96.5 to 100.2% for brain homogenate, for all target concentrations. The developed assay has been successfully applied for a brain distribution study in mice at an oral dose of 5 mg/kg.

► This is the first study to describe a sensitive and precise LC–MS assay for cediranib. ► This assay allows small specimen volumes and adequate detectability to use in tissue distribution studies. ► We have employed the assay in a brain distribution study in the mouse, to examine different mechanisms that limit the CNS distribution of cediranib. ► The assay is generally applicable to a variety of pharmacokinetic and in vitro cell culture experiments.