INNOVATIVE APPROACHES IN THE QUANTITATIVE ANALYSIS OF IBRUTINIB

Sneha N. U.*, Suresha D. N., Naveen Kumar G. S.

ABSTRACT

Ibrutinib is an irreversible Bruton’s tyrosine kinase (BTK) inhibitor widely used in the treatment of various B-cell malignancies, including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström’s macroglobulinemia. Accurate and reliable analytical methods are essential for its quality control, stability evaluation, and bioanalysis. This review presents a comprehensive overview of analytical techniques reported for the determination of ibrutinib in bulk drug, pharmaceutical formulations, and biological matrices. Various spectrophotometric, RP-HPLC, UPLC, and LC-MS/MS methods have been discussed with respect to their sensitivity, linearity, accuracy, precision, and validation according to ICH guidelines. Spectrophotometric methods offer simplicity and cost effectiveness but exhibit lower sensitivity, whereas RP-HPLC methods demonstrate high accuracy, robustness, and reproducibility, making them suitable for routine pharmaceutical analysis. Advanced UPLC and LC-MS/MS techniques provide enhanced sensitivity at nanogram levels and are particularly valuable for impurity profiling, stability studies, and pharmacokinetic investigations. Stability studies consistently indicate that ibrutinib is susceptible to degradation under acidic, basic, and oxidative conditions while remaining stable under neutral, photolytic, and thermal stress. Overall, this review highlights RP-HPLC as the preferred method for quality control applications, with UPLC and LC-MS/MS serving as indispensable tools for advanced bioanalytical and stability assessments.

Keywords: Ibrutinib; Bruton’s tyrosine kinase; RP-HPLC; UPLC; LC-MS/MS; Stability studies.