Abstract
•The first LC-MS/MS method for the determination of erdafitinib in human plasma.•Full method validation according to FDA and EMA bioanalytical method validation guidelines.•Optimization of SPE method for extracting erdafitinib from plasma with high percent recovery.•Applicable method for therapeutic drug monitoring and pharmacokinetic studies.•The proposed method was evaluated for its greenness.
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 96.49–103.88% 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.