DEVELOPMENT AND VALIDATION OF AN LC-MS/MS METHOD FOR THE QUANTIFICATION OF REPOTRECTINIB IN HUMAN PLASMA

Objective: The primary aim of this study is to develop and verify a linear, exact, and specific LC-ESI-MS/MS technique for the measurement of Repotrectinib. Methods: Chromatographic resolution was attained using an ODS Zorbax C18 column (50 mm×4.6 mm, 2.1 µm) and a mobile phase comprising methanol, 0.1% formic acid, and acetonitrile in a ratio of 50:15:35, with a flow rate of 0.5 ml/min from the stationary phase. The procedure was conducted by observing the defined ionic transitions of m/z 356.15/318.13 for Repotrectinib and 478.09/451.08 for the Apalutamide internal standard in multiple reaction monitoring. Results: The linear regression equation was y = 0.0001x+0.0012, with a coefficient of determination (r²) of 0.9997. The percentage coefficient of variation results for the matrix effect for Low-QC and High-QC levels were 2.90% and 3.41%, respectively. The average recovery percentages for Repotrectinib at High-QC (11.25 µg/ml), MQC (7.50 µg/ml), and Low-QC (1.05 µg/ml) were 103.27%, 97.26%, and 96.34%, respectively. The measured values ranged from 2.00% to 4.03% for the QC samples at concentrations of 0.375, 1.05, 7.50, and 11.25 µg/ml. Conclusion: The created approach underwent validation in accordance with FDA guidelines and is applicable for the assessment of repotrectinib in biological samples for quality control, forensic analysis, and bioavailability investigations.