Characterization of Degradation Products and Drug-Excipient Interaction Products of Erdafitinib by LC-Q-TOF-MS/MS and NMR

Erdafitinib is a potent and selective tyrosine kinase receptor inhibitor used to treat advanced or metastatic urothelial carcinoma. The purpose of this study is to explore the degradation behavior of erdafitinib when exposed to various stress conditions as per ICH, along with its compatibility with various excipients under accelerated stability conditions. The degradation and interaction products formed under various conditions were separated using phenomenix Gemini C18 column (250 x 4.6 mm; 5 & mu;m) with 10 mM ammonium acetate (pH 4.50) buffer and methanol as mobile phase in gradient elution mode at a flow rate of 1 mL/min. Erdafitinib was found to be labile in hydrolytic, photolytic and oxidative stress conditions. It was also found to be incompatible with polyethylene glycol-4000, polyvinyl pyrrolidone-K30, crospovidone and carboxymethylcellulose when exposed to accelerated stability conditions. A total of eight novel degradation products and one interaction product were generated. LC-Q TOF-MS/MS studies were conducted to propose the structures of degradation and interaction products formed by comparing with the fragmentation pattern of the drug. NMR study was also conducted to confirm the chemical structures of two degradation products (DP7 and DP8). Subsequently, the degradation pathway of erdafitinib was also laid down. Further, in silico toxicity and mutagenicity data was generated using DEREK and Sarah software. DP1, DP4, DP5, DP6, DP7 and DP9 show mutagenicity as endpoint.