Solid phase extraction and high-performance liquid chromatographic determination of lazertinib in human plasma.

Abstract

Lazertinib is a novel third-generation tyrosine kinase inhibitor (TKI) developed for the treatment of epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC). Reports on previous EGFR-TKIs have detailed significant associations between blood drug concentration and efficacy. In addition, significantly elevated blood concentrations of lazertinib have been observed in Asians compared to Caucasians, suggesting the influence of interethnic variability. In this study, we developed and validated a method to determine lazertinib concentrations in human plasma for therapeutic drug monitoring (TDM). Lazertinib and its internal standard, sotorasib, were extracted by solid-phase extraction using an Oasis hydrophilic lipophilic balance cartridge. Chromatographic separation was performed on a reversed-phase column with 0.5% KH₂PO₄ (pH 4.5) and acetonitrile (52:48, v/v) as the mobile phases in an isocratic elution mode with a flow rate of 1.0 mL/min. The detection wavelength was 296 nm. The calibration curves were linear in the range of 25-2,000 ng/mL, with a coefficient of determination (r²) of 0.9997. The accuracy and precision of all validation experiments were within the criteria set by the Food and Drug Administration guidelines. This study represents the first development and validation of a method for quantifying lazertinib in human plasma. This study is expected to facilitate the widespread use of TDM in studies on lazertinib.