Bioanalytical Method Validation and Bioequivalence Study of Ibrutinib in Human Plasma Using LC -MS/MS: An Advanced Approach

This study presents a comprehensive bioanalytical method validation and bioequivalence analysis for ibrutinib, a Bruton’s tyrosine kinase inhibitor, in human plasma samples. The method employs liquid chromatography-tandem mass spectrometry (LC-MS/MS) for quantification, utilizing apixaban as an internal standard. Method validation adhered to ICH M11 guidelines, assessing parameters such as specificity, carry-over, lower limit of quantitation (LLOQ), calibration curve linearity, accuracy, precision, matrix effects, and stability under various conditions. Calibration curves exhibited strong linearity across a range of 1.5–44 ppb (R > 1.00), with an LLOQ of 1.5 ppb demonstrating a signal-to-noise ratio exceeding 11. The method demonstrated robust specificity with minimal interference, as well as high precision and accuracy, with intra- and inter-day deviations within acceptable limits (<15%). Stability assessments, including freeze-thaw, short-term, and long-term analyses, confirmed analyte integrity under varied conditions. The bioequivalence study compared test and reference formulations of ibrutinib in 26 healthy volunteers over multiple time points, with pharmacokinetic parameters including C_max and AUC analyzed for equivalence. Results affirmed bioequivalence between formulations, meeting regulatory criteria. This validated method provides a reliable tool for therapeutic drug monitoring and pharmacokinetic studies of ibrutinib, contributing to optimized clinical outcomes and regulatory compliance.

Bioanalytical Method Validation and Bioequivalence Study of Ibrutinib in Human Plasma Using LC -MS/MS: An Advanced Approach Keywords:

Ibrutinib , Bioequivalence , LC-MS/MS , Analytical Method Validation , Pharmacokinetics