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Preclinical Pharmacokinetics of Erdafitinib, an FGFR Tyrosine Kinase Inhibitor, via LC-MS/MS in Sprague Dawley Rats
Rajesh Kumar Boggavarapu1, Jithendra Chimakurthy1
1Department of Pharmaceutical Sciences, Vignan's Foundation for Science, Technology and Research, Guntur, Andhra Pradesh, India.
Introduction:
Erdafitinib is a pan-FGFR tyrosine inhibitor approved for urothelial carcinoma, with growing interest in its broader anticancer applications. Accurate quantification in preclinical models is essential for understanding pharmacokinetics and optimizing therapeutic use. Developing a sensitive, economical bioanalytical method ensures reliable drug monitoring, supporting translational research and regulatory compliance in oncology drug development.
Methods:
Rat plasma samples were processed by protein precipitation, and analytes were separated on a reverse-phase column using a gradient mobile phase. Detection employed LC-MS/MS in positive ionization mode with multiple reaction monitoring (MRM), monitoring m/z 447.1 → 362.1 for erdafitinib and m/z 515.2 → 276.0 for internal standard. The total run time was 2.0 min.
Results:
The method demonstrated excellent linearity across 1.0-1000 ng/mL with a lower limit of quantification of 1.0 ng/mL. Precision was < 12% and accuracy within 100% ± 6% across the calibration range. The assay was validated according to US FDA M10 guidelines and successfully applied to pharmacokinetic studies in Sprague Dawley rats, enabling reliable plasma concentration profiling of erdafitinib.
Conclusions:
This validated LC-MS/MS method provides a rapid, sensitive, and cost-effective approach for erdafitinib quantification in preclinical plasma samples. Its application to pharmacokinetic studies supports drug development by enabling accurate assessment of exposure and disposition, thereby advancing pharmacological understanding and facilitating translation to clinical oncology research.
Insights
A new LC-MS/MS method accurately quantifies erdafitinib in rat plasma, crucial for understanding its anticancer effects. This bioanalytical method supports oncology drug development and translational research.
Area of Science:
- Pharmacology
- Analytical Chemistry
- Oncology Drug Development
Background:
- Erdafitinib is a pan-FGFR tyrosine inhibitor with potential anticancer applications beyond urothelial carcinoma.
- Accurate quantification in preclinical models is vital for pharmacokinetic studies and optimizing erdafitinib's therapeutic use.
- A sensitive and economical bioanalytical method is essential for reliable drug monitoring in oncology research.
Purpose of the Study:
- To develop and validate a sensitive, rapid, and cost-effective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for quantifying erdafitinib in rat plasma.
- To support preclinical pharmacokinetic studies and advance the understanding of erdafitinib's disposition in oncology drug development.
Main Methods:
- Rat plasma samples were prepared using protein precipitation.
- Erdafitinib and an internal standard were separated using reverse-phase liquid chromatography (LC) with a gradient mobile phase.
- Detection was performed using LC-MS/MS with multiple reaction monitoring (MRM) in positive ionization mode, achieving a total run time of 2.0 minutes.
Main Results:
- The method exhibited excellent linearity over a concentration range of 1.0-1000 ng/mL, with a lower limit of quantification (LLOQ) of 1.0 ng/mL.
- Assay precision was within 12%, and accuracy was within ±6% across the calibration range.
- The method was validated per US FDA M10 guidelines and successfully applied to Sprague Dawley rat plasma samples for pharmacokinetic profiling.
Conclusions:
- A validated LC-MS/MS method offers a rapid, sensitive, and cost-effective means for quantifying erdafitinib in preclinical plasma.
- This assay facilitates accurate assessment of erdafitinib exposure and disposition, crucial for advancing pharmacological understanding.
- The method supports oncology drug development by enabling reliable pharmacokinetic studies and facilitating translation to clinical research.
