Comprehensive Bioequivalence Analysis of Tofacitinib 11 mg in Human Plasma Using Advanced LC-MS/MS Techniques
Keywords:
Tofacitinib, bioequivalence, LC-MS/MS, analytical method validation, pharmacokineticsAbstract
This study presents a detailed bioequivalence evaluation of Tofacitinib 11 mg formulations through rigorous analytical and statistical methodologies, aligning with EMEA and ICH M10 guidelines. Employing liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization, the study achieves high sensitivity and specificity for Tofacitinib quantification. The analytical method was validated across critical parameters: linearity, accuracy, precision, matrix effects, and stability, ensuring robust results. Methodological precision was established through repeatability and intermediate precision tests, with results indicating %RSD values within acceptable thresholds. Matrix effect assessments confirmed negligible plasma interference, validating the method's reliability in complex biological matrices.
Stability tests—including freeze-thaw, short-term, and long-term stability—demonstrated the analyte's integrity under varied conditions. The study also delineates a comprehensive calibration curve, validating quantification limits as low as 1.5 ppb. Pharmacokinetic data from human subjects further support bioequivalence, with parameters such as Cmax, AUC0–t, and t1/2 showing consistent profiles across test and reference formulations. These findings affirm the test formulation's equivalence in terms of safety and efficacy. This work not only establishes a robust methodological framework for Tofacitinib analysis but also provides critical insights into its pharmacokinetic behavior, paving the way for its broader clinical application.
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