Ultra-performance liquid chromatography method for the determination of tyrosine kinase inhibitors in human plasma

Tyrosine kinase inhibitors (TKIs) are a class of targeted drugs with antiangiogenic and antitumor activities. They are increasingly used in the treatment of malignant pathologies like advanced or metastatic renal cell carcinoma and advanced gastro-intestinal stromal tumors.
Their mode of action consists in an inhibition of multiple receptors tyrosine kinase (RTKs) that are involved in tumor growth, pathologic angiogenesis and metastatic progression such as platelet-derived growth factor receptors (PDGF-R) and vascular endothelial growth factor receptors (VEGF-R) in particular. Due to inter-individual metabolic variability, an accurate therapeutic drug monitoring represents a key element for the patient treatment [1-4].
Three TKIs tested in a clinical research study (namely sunitinib (a), axitinib (b) and pazopanib (c)) are under investigation.

The aim of this work is to develop a similar analytical procedure able to identify and quantify the three TKIs but also the active metabolite of sunitinib (n-desethyl sunitinib) in human plasma.
A fast ultra-performance liquid chromatography (UPLC) method coupled to UV detection after a pre-extraction step using solid phase extraction (SPE) cartridges or µElution 96-well plate (µSPE) will be here described.
The preliminary results of the method validation using an internal standard (IS) will be also presented.