Isolation, Identification and Characterization of Gefitinib Novel Degradation Products by\nNMR and HRMS, Method Development and Validation by UPLC

Abstract

Gefitinib (GFT) sold under the brand name Iressa, is a medication used to treat certain type of breast,\nlung and other cancers, Gefitinib was subject to stress degradation under acidic, basic, peroxide mediated\noxidation, photolytic and thermal degradation. The stress degradation was performed according to\nICH guidelines Q1A(R2) and the drug was inert under thermal and photolytic conditions. One degradant\nis identified in acid hydrolysis referred as 7-methoxy-6-(3-morpholinopropoxy) quinazolin-4(3H)-one\n(GFT-DP1) and two degradants were formed in peroxide mediated hydrolysis referred as 4-(3-((4-((3-\nchloro-4-fluorophenyl)amino)-7-methoxy-1-oxidoquinazolin-6-yl)oxy)-propyl)morpholine-4-oxide\n(GFT-DP2) and 4-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)-propyl)-\nmorpholine-4-oxide (GFT-DP3). In present study, all the novel three degradation product structures\nwere confirmed by HRMS and 1D (1H, 13C) and 2D (COSY, HSQC and HMBC) based on 1D and 2D\nNMR data proton and carbon chemical shift values assigned exactly for all degradation products. A\nstability indicating RP-UPLC method was developed and validated with shorter run time and this\nmethod was validated in terms of linearity, specificity, accuracy, LOD and LOQ.