Separation and Characterization of New Forced Degradation Products of Dasatinib in Tablet Dosage Formulation Using LC–MS and Stability-Indicating HPLC Methods

Abstract

Dasatinib is a protein kinase inhibitor used for the treatment of chronic myelogenous leukemia and acute lymphoblastic leukemia. Dasatinib along with its six known organic impurities were separated using the reversed-phase high performance liquid chromatography with C18 column and mobile phases consisting of gradient mixture of 20 mM potassium phosphate buffer at pH 6.0 with 1-octanesulphonic acid sodium salt (0.1%, w/v), acetonitrile and ultrapure water. This method was successfully tested with liquid chromatography coupled mass-spectrometry to elucidate the chemical structure of newly formed degradation product of Dasatinib which was identified by comparing its retention time and mass-spectra with literature data. Stability-indicating characteristics of developed HPLC method was assessed using stress testing [5 N HCl at 90 °C/1 h, 5 N NaOH at 90 °C/1 h, H2O at 90 °C/1 h, 30% H2O2 (w/w) at 25 °C ± 5 °C/1 h, dry heat at 105 °C/24 h and UV (200 W h m−2) and fluorescent light (1.2 million lux-h)] and was validated as per ICH Q2(R1). For Dasatinib and its six impurities, the quantification limits, linearity and recoveries were found in range of 0.19–0.21 μg/mL, 0.2–3.0 μg mL−1 (R2 > 0.995) and 85.5–107.0%, respectively. The developed HPLC method will also suffice the suitability for impurity profiling and assay of Dasatinib in bulk drugs and pharmaceutical formulations.