Development and Validation of Stability Indicating Liquid Chromatographic Method for Vandetanib: Application to Degradation Studies by LC-MS

Abstract

Objective: The central goal of this research was to formulate and validate a stability-demonstrating assay approach using reverse-phase high-performance liquid chromatography (RP-HPLC) for the assessment of vandetanib, its primary degradation products, and their respective degradation pathways, which were identified and characterized using liquid chromatography-electrophore spray ionization-mass spectrometry (LC-ESI-MS).Methods: The method was designed and developed by employing a Grace C18 column (250 x 4.6 mm x4.0 μm) and deploying a mixture of methanol and 0.1% formic acid in H2O (in a proportion of 90:10, v/v) as the mobile phase, with a flow rate maintained at 1-mL/min. The analytes were detected at a wavelength of 249 nm. Additionally, vandetanib was subjected to various stress conditions, including acidic, alkaline, oxidative, thermal, and photolytic degradation, to unearth the degradation paths for the principal degradation products.Results: The approach was meticulously formulated and validated to ensure robustness, linearity, precision, accuracy, and linear regression analysis data. A high correlation coefficient of 0.9985 was obtained in the 2 to 12 μg/mL concentration range, demonstrating a robust linear relationship. Moreover, the limit of detection (LoD) and the limit of quantification (LoQ) were found to be 0.166 and 0.503 μg/mL, respectively. In the stress degradation studies, we noticed that vandetanib degraded in alkaline and acidic mediums. The liquid chromatography-mass spectrometry (LC-MS) technique was used to characterize the degradation products.Conclusion: The devised method demonstrated itself to be quick, sensitive, precise, accurate, and robust for the vandetanib analysis, thereby facilitating its routine testing.