HPLC-UV determination of erdafitinib in mouse plasma and its application to pharmacokinetic studies
Tarek Elawady1, Alaa Khedr2, Nahed El-Enany3
1Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Mansoura University, P.O. Box 35516, Mansoura, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, P.O. Box 80260, Jeddah 21589, Saudi Arabia.
Abstract:
Erdafitinib is a recently approved fibroblast growth factor receptor (FGFR) inhibitor. It is the first treatment targeting susceptible FGFR genetic alterations for patients with metastatic bladder cancer. A simple validated HPLC-UV method was developed for the determination of erdafitinib in mouse plasma. Erdafitinib and internal standard (rivaroxaban) were efficiently separated on Eclipse plus C18 column (4.6 × 100 mm, 3.5 µm). The mobile phase consisted of acetonitrile and 0.01 M ammonium acetate aqueous solution, adjusted to pH 4.4 with acetic acid (26:74, v/v) and it was eluted isocratically at a flow rate of 1.2 mL/min. The UV detection was at 292 nm and the total run time for each sample was 11 min. The method linearity was validated over the range of 0.05-2.00 µg/mL (r2 ≥ 0.9992) and the lower limit of quantification (LLOQ) was 0.05 µg/mL. The within-run and between-run accuracies were 98.56 and 99.24%, respectively while the CV of the method precision did not exceed 6.52%. Plasma samples were extracted using a solid phase extraction procedure and the extraction recoveries were 97.90 ± 4.58%. The method was optimized for the sensitive determination of the studied drug in mouse plasma and was successfully applied to its pharmacokinetic studies.
Insights
A new HPLC-UV method accurately quantifies erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor, in mouse plasma. This method supports pharmacokinetic studies for this important metastatic bladder cancer treatment.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Oncology
Background:
- Erdafitinib is a novel fibroblast growth factor receptor (FGFR) inhibitor.
- It represents a targeted therapy for metastatic bladder cancer with specific FGFR genetic alterations.
- Accurate quantification in biological matrices is crucial for pharmacokinetic evaluation.
Purpose of the Study:
- To develop and validate a simple, sensitive High-Performance Liquid Chromatography with Ultraviolet detection (HPLC-UV) method.
- To determine erdafitinib concentrations in mouse plasma.
- To support pharmacokinetic studies of erdafitinib.
Main Methods:
- High-Performance Liquid Chromatography with Ultraviolet detection (HPLC-UV) using an Eclipse plus C18 column.
- Isocratic elution with a mobile phase of acetonitrile and ammonium acetate buffer (pH 4.4).
- UV detection at 292 nm; solid phase extraction for plasma sample preparation.
Main Results:
- The method demonstrated excellent linearity (r² ≥ 0.9992) over the range of 0.05-2.00 µg/mL.
- The lower limit of quantification (LLOQ) was 0.05 µg/mL.
- High accuracy (98.56-99.24%) and precision (CV ≤ 6.52%) were achieved with efficient extraction recovery (97.90 ± 4.58%).
Conclusions:
- A validated, simple, and sensitive HPLC-UV method for erdafitinib determination in mouse plasma was successfully developed.
- The method is suitable for supporting pharmacokinetic studies.
- This analytical method aids in understanding the behavior of erdafitinib in vivo.
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