Study of erdafitinib stress degradation behavior using HPLC-UV analysis and multistage fragmentation ion trap mass spectrometry

Erdafitinib is a fibroblast growth factor receptor inhibitor, which has been recently approved for the treatment of urothelial carcinoma. The stress degradation behavior of erdafitinib was examined using a validated stabilityindicating high-performance liquid chromatography method. The study was extended to investigate the fragmentation pathways of erdafitinib using ion trap mass spectrometry. Six degradation products and an impurity were characterized depending on their multistage fragmentation pattern. The degradation products formed under different stress conditions showed molecular masses of 443, 477, 433, 479, 463, and 459. The molecular mass of the detected impurity was 525. The drug and its related substances were efficiently separated on an Eclipse Plus C18 column (4.6 x 100 mm, 3.5 mu m). An isocratic mobile phase consisting of acetonitrile and 0.01 M ammonium formate in water containing 0.1% formic acid (26:74, v/v) was used at a flow rate of 0.5 mL/min. Erdafitinib was exposed to oxidative, photolytic, acidic, basic, and thermal hydrolysis as recommended by ICH guidelines. The drug was found to be more sensitive to oxidative hydrolysis and slightly sensitive to acidic and photolytic hydrolysis. The method was fully validated according to ICH guidelines. The limit of detection and quantitation were 0.2 and 0.5 mu g/mL, respectively. The relative standard deviations of intraday and interday precisions were not more than 1.99%. The developed method was successfully applied for the determination of erdafitinib in bulk and laboratory-prepared tablets.

Automated summary

This study investigates the degradation behavior and fragmentation pathways of Erdafitinib using validated stability-indicating HPLC and ion trap mass spectrometry methods. Six degradation products and an impurity were characterized and a reliable determination method was developed. The study provides important insights into the stability and degradation of Erdafitinib.