Development of a sensitive plasma lenvatinib quantification method and validation in thyroid cancer patients

Context: Lenvatinib (LEN) is effective in the treatment of radioactive iodine refractory differentiated thyroid cancer (DTC), though it is associated with frequent and potentially severe adverse events (AEs). The dose dependency of LEN-related toxicity remains unclear, since no data are available on this topic. Objective: This study aimed to investigate the relationship between LEN dose and plasma concentrations in real-life patients by a novel and validated method for quantifying LEN in plasma samples. Design and setting: A sensitive high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) assay for LEN quantification in plasma was set up, with a wide analytical range (0.7-500 ng/mL). Consecutive plasma samples from 19 patients with radioactive iodine-refractory, metastatic DTC were analyzed. Results: A positive correlation between the administered LEN dose and plasma concentrations was found, particularly in patients on low doses (