Development of a simple high-performance liquid chromatography-ultraviolet detection method for selpercatinib determination in human plasma.

Abstract

Selpercatinib is a selective rearranged during transfection (RET) kinase inhibitor effective for the treatment of RET-positive non-small cell lung cancer, thyroid cancer, and other cancers. However, its clinical use requires careful management because of dose-dependent adverse effects and pharmacokinetic interactions. Given the multiple factors influencing selpercatinib blood levels, we hypothesized that establishing a therapeutic drug monitoring system for selpercatinib could help reduce adverse events and optimize efficacy. Therefore, we herein developed a high-performance liquid chromatography-ultraviolet (HPLC-UV) method for measuring selpercatinib blood levels to facilitate therapeutic drug monitoring in clinical practice. Proteins were precipitated with acetonitrile, and selpercatinib and the internal standard (gefitinib) were separated via HPLC-UV. The calibration curve was linear over 0.5-8.0 µg/mL with a coefficient of determination (r²) equaling 0.9996. Intra- and interday validation coefficients were both under 2.80%. The corresponding measurement precision ranged from - 1.50% to 12.60% and - 1.32% to 7.50%, respectively, with recoveries exceeding 94.43%. Thus, this study establishes a simple and sensitive method for quantifying selpercatinib in human plasma. Future studies will analyze plasma samples from patients treated with selpercatinib and utilize this method to explore the relationships among plasma concentration, efficacy, and adverse events to define the therapeutic concentration range.