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A validated reverse phase stability-indicating HPLC method for bortezomib in the presence of degradation products and its process-related impurities
Authors: Jagadeswara Rao K, Mohan B, Venugopal NVS, Murali Mohan SV, Rama Rao Malla
Number of views: 861
Degradation pathway of bortezomib was established as per ICH recommendations in terms of validated and stability
indicating reverse phase liquid chromatographic method. Bortezomib was subjected to stress using conditions of acid, base,
oxidation, thermal and photolysis. Significant degradation was observed in acid and base stress conditions. Ten impurities were
studied and the major degradant was hydroxyamide impurity. The stress samples were assayed against a qualified reference
standard and the mass balance is found close to 98.2%. Efficient chromatographic separation was achieved on a Zorbax Extend
C18(100 x 4.6 mm, 1.8 μm) stationary phase with simple mobile phase combination In the developed LC method, the resolution
between bortezomib and ten potential impurities such as Imp-A, Imp-B, Imp-C, Imp-D, Imp-E, Imp-F, Imp-G, bortezomib
isomer, hydroxyamide and bortezomib ester) was found to be greater than 2.0. Regression analysis showed r value (correlation
coefficient) of greater than 0.999 for bortezomib and ten potential impurities. This method was capable of detecting the
impurities of bortezomib at a level of 0.02% with respect to test concentration of 2.0 mg/mL. The developed rapid LC method
was validated with respect to specificity, linearity, range, accuracy, precision and robustness for impurities.