LC-MS/MS determination of erdafitinib in human plasma after SPE: Investigation of the method greenness

Abstract Erdafitinib is an oral pan-fibroblast growth factor receptor (FGFR) inhibitor. It has been recently approved on April 2019 by FDA for patients with urothelial carcinoma that has susceptible FGFR3 or FGFR2 genetic alterations. A sensitive and reproducible bioanalytical LC-MS/MS method was established and validated for the determination of erdafitinib in human plasma samples. A solid phase extraction procedure was optimized for sample pretreatment with mean extraction recoveries not less than 95.70 ± 1.23 %. Antipyrine was used as internal standard. Effective separation of erdafitinib and antipyrine was achieved on an Eclipse plus C18 column (3.0 × 150 mm, 5 µm) with isocratic mobile phase consisting of acetonitrile and 0.01 M ammonium formate aqueous solution containing 0.1 % formic acid (35:65, v/v) at a flow rate of 0.6 mL/min. The method was linear over the range of 3-1000 ng/mL (r2 ≥ 0.9991) with a lower limit of quantification (LLOQ) at 3.0 ng/mL. Accuracies were within 96.49 % to 103.88 % and the relative standard deviation of within-run and between-run precision was less than 7.47 %. The drug was sufficiently stable under different analytical conditions. The developed method greenness was investigated. The proposed method is the first LC-MS/MS method for the determination of erdafitinib in human plasma and it is suitable for in-patients’ therapeutic drug monitoring.