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Implementation of DoE and Risk-Based Enhanced Analytical Quality by Design Approach to Stability Indicating RP-HPLC Method for Stability Study of Bosutinib.

BACKGROUND
Bosutinib is a small molecule BCR-ABL, and src tyrosine kinase inhibitor used for the treatment of chronic myelogenous leukaemia. According to published literature, no stability-indicating RP-HPLC method has been reported yet for estimation of bosutinib.


OBJECTIVE
Hence, the stability-indicating RP-HPLC method has been developed for the stability study of bosutinib using risk and DoE-based enhanced analytical quality by design approach.


METHODS
The risk-based analytical quality by design approach was applied by risk parameter identification and risk assessment by risk priority number (RPN) ranking and filtering method as per International Council for Harmonisation (ICH) Q9 guideline. The DoE-based AQbD approach was implemented by response surface analysis using a central composite design. The risk of critical method risk parameters was mitigated by navigation of design space and framing of control strategy.


RESULTS
The chromatographic separation was performed using a C18 column and acetonitrile-1.0%, v/v triethylamine in water (pH 7.0 adjusted by ortho-phosphoric acid). The developed method was validated according to the ICH Q2 (R1) guideline.The developed and validated method was applied for the assay of bosutinib in pharmaceutical dosage forms. The developed method was extended for oxidative degradation kinetic study of bosutinib at different pH conditions.


CONCLUSION
The developed RP-HPLC method can be used as analytical tool for quality control and stability study of pharmaceutical dosage forms of bosutinib in pharmaceutical industry.


HIGHLIGHTS
Development and validation of Stability indicting RP-HPLC method for estimation of bosutinib by implementation of DoE and risk-based enhanced AQbD approach. Application of method for assay of pharmaceutical dosage forms and oxidative degradation kinetic study.