UPLC-DAD method validation by accuracy profiles approach 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. Due to inter-individual metabolic variability, an accurate therapeutic drug monitoring represents a key element for the patient treatment. Three TKIs tested in a clinical research study (namely sunitinib, axitinib and pazopanib) are under investigation.
In this frame, we developed a similar and fast ultra-performance liquid chromatography (UPLC) method coupled to DAD detection after a pre-extraction step using µElution 96-well plate (µSPE) able to discriminate and quantify TKIs (including also the active metabolite of sunitinib (n-desethyl sunitinib)) in human plasma.
The analytical procedure was validated using the accuracy profiles approach and permit us to quantify TKIs in human plasma in the clinical research targeted range with LOQ at 10 ng/mL for sunitinib, at 15 ng/mL for n-desethyl sunitinib and axitinib and at 20 µg/mL for pazopanib.