Using an innovative quality-by-design approach for the development of a stability-indicating UPLC/Q-TOF-ESI-MS/MS method for stressed degradation products of imatinib mesylate

Abstract

A stability-indicating UPLC/Q-TOF-ESI-MS/MS method has been developed for the simultaneous determination of imatinib mesylate (IMM) and its impurity and degradation products in the active pharmaceutical ingredient (API) and drug products. Gradient elution of 0.1% g mL⁻¹ ammonium formate buffer at pH 8.57 and acetonitrile were used as the mobile phase and a Waters Acquity UPLC CSH C18, 100 mm × 2.1 mm, 1.7 μm particle size column was utilized as the stationary phase. Forced degradation, such as acid and base hydrolysis, and oxidative stress conditions of IMM were carried out to prove the stability-indicating performance of the method. The quality-by-design (QbD) principle was applied to the method development approach and the chromatography modeling software DryLab®2000 plus and Design Expert®8.0.6 were used to optimize the chromatographic method. The robustness study (Design Space) was performed by varying three critical chromatographic parameters (flow rate, temperature, and pH) at 3 levels (+1, 0, and −1). The result showed that baseline separation of all peaks of IMM and its impurity and degradation products could be achieved and a resolution of 2.0 could be reached in all experiments. The UPLC method was validated for specificity, linearity, accuracy, precision and robustness in compliance with the ICH guideline Q2 (R1). The method we developed was a fast, robust and reliable UPLC method with higher suitability and specificity. Furthermore, elemental composition and major fragments of the impurity and degradation products of IMM were characterized through the optimized UPLC/Q-TOF-MS/MS analysis.