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A Validated Stability-Indicating UF LC Method for Bortezomib in the Presence of Degradation Products and its Process-Related Impurities

Venkataramanna M, K Sudhakar Babu and S.K.C.Anwar

Degradation pathway for bortezomib is established as per ICH recommendations by validated and stability indicating reverse phase liquid chromatographic method. Bortezomib is subjected to stress conditions of acid, base, oxidation, thermal and photolysis. Significant degradation is observed in acid and base stress conditions. Five impurities are studied and the major degradant (RRT about 1.19) was identified by LC-MS and spectral analysis. The stress samples are assayed against a qualified reference standard and the mass balance is found close to 99.5%. Efficient chromatographic separation is achieved on a Shim pack XR-ODS-II(100X3 mmx2.2 μm) stationary phase with simple mobile phase combination delivered in gradient mode and quantification is carried at 270 nm at a flow rate of 0.6 mL min. In the developed LC method the resolution between bortezomib and five potential impurities (imp-1, imp-2, imp-3, imp-4 and imp-5) is found to be greater than 2.0. Regression analysis shows an r value (correlation coefficient) of greater than 0.999 for bortezomib and five potential impurities. This method is capable to detect the impurities of bortezomib at a level of 0.020 % with respect to test concentration of 2.0 mg mL for an 8-μL injection volume. The developed rapid LC method is validated with respect to specificity, linearity & range, accuracy, precision and robustness for impurities determination.