Method validation and characterization of stress degradation products of gefitinib through UPLC-UV/PDA and LC–MS/TOF studies

Abstract

Gefitinib was subjected to stress degradation conditions of hydrolysis (neutral, acidic and alkaline), oxidation, photolysis and thermal stress, as per the ICH guideline Q1A(R2). A UPLC-UV/PDA based stability-indicating method was developed for the drug and validated as per ICH guidelines. The drug showed significant degradation under acidic/alkaline/neutral hydrolytic, acidic/alkaline/neutral photolytic, thermal and oxidative stress conditions. In total, seven degradation products (I-VII) were formed, which could be separated from the drug by UPLC on a Kinetex® C18 (100 mm × 4.6 mm; 2.6 μ) column using isocratic elution method. Detection wavelength was selected as 257 nm. The developed method was extended to UPLC-MS/TOF studies and accurate mass spectral data was used to identify and characterize the degradation products. Out of the seven degradation products, five products (I-II; V-VII) could be characterized through their MS/TOF spectral data. The degradation pathway of the drug leading to generation of various products was postulated and this has not been reported so far.