Bioequivalence Analysis of Regorafenib in Human Plasma Using LC-MS/MS: Validation and Application
Keywords:
Bioequivalence, Regorafenib, LC-MS/MS, Human Plasma, Pharmacokinetic, Validation, Analytical Method, Drug Development, ICH M10, EMEA GuidelinesAbstract
This study presents a comprehensive bioequivalence analysis of regorafenib in human plasma using a validated LC-MS/MS method. Regorafenib, a multi-kinase inhibitor, was analyzed in plasma samples collected from volunteers administered both test and reference formulations. The analytical method employed included the use of sorafenib as an internal standard, ensuring accuracy and precision. Validation parameters, such as specificity, linearity, precision, and accuracy, were evaluated in accordance with the ICH M10 and EMEA guidelines. The method demonstrated robust performance with calibration curves showing linearity in the range of 0.5–40 ppb and acceptable precision, with %RSD values below 10%.
Bioequivalence studies were conducted on 25 healthy volunteers under a crossover design. Plasma concentrations of regorafenib were quantified at multiple time points, enabling the calculation of pharmacokinetic parameters, including Cmax, Tmax, and AUC. Results indicated that the test and reference formulations were bioequivalent, with geometric mean ratios falling within the acceptable range of 80–125%. The developed LC-MS/MS method, characterized by its high sensitivity and selectivity, proved effective for routine bioequivalence studies of regorafenib.
This research highlights the importance of rigorous validation and methodological precision in bioequivalence studies, ensuring reliability in drug evaluation and regulatory compliance.
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References
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