BIOANALYTICAL LC–MS/MS METHOD DEVELOPMENT AND VALIDATION FOR THE DETERMINATION OF REPOTRECTINIB IN PLASMA

A new, precise, and linear LC-MSMS method was established and verified for the purpose of quantifying Repotrectinib in plasma. The internal standard, Erlotinib, and Repotrectinib were separated by chromatography using a Zorbax C18 column with dimensions of 150 mm×2.1mm and 5.0 μm particle size. A 0.7 mL/min flow rate was supplied as mobile phase, which consisted of methanol, 0.1% HCOOH, and acetonitrile at a ratio of 20:15:65. Repotrectinib concentrations ranging from 3.8 to 1550.0 ng/mL were linearly resolved by the approach. The lower limit of quantification was determined to be 3.8 ng/mL. The intra-batch precision and accuracy ranged from 93.69% to 96.98%, with precision values falling between 3.17% and 4.97%. The accuracy across different batches varied from 95.04% to 96.52%, while the precision fell within the range of 3.33% to 4.52% (CV). The average total recovery at quality control levels for Repotrectinib ranged from 93.84% to 103.85%. The estimation of the recovery of the internal standard was conducted using equivalent medium quality control sample solutions as a reference point. The %CV for the matrix effect of low and high-quality control samples was 3.54% and 4.48% for Repotrectinib. The developed method successfully can be successfully applied to study bioequivalence and bioavailability parameters, and also in quality control labs.