Determination of Cediranib in Mouse Plasma and Brain Tissue Using High-Performance Liquid Chromatography-Mass Spectrometry

摘要

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 mouse brain distribution study in mice at an oral dose of 5 mg/kg.