Quantification of Vactosertib an Inhibitor of TGFBR1 by LC-MS/MS in Rat Plasma and Its Pharmacokinetic Profiling
Rajesh Kumar Boggavarapu1, Jithendra Chimakurthy1, Sathish Kumar Konidala1
1Department of Pharmaceutical Sciences, School of Biotechnology and Pharmaceutical Sciences, Vignan's Foundation for Science, Technology and Research, Guntur, India.
Abstract:
Vactosertib, an inhibitor of transforming growth factor β-receptor type-1 (TGFBR1) effective in preventing tumor cell proliferation, is approved for treating various cancers by FDA. The literature revealed that no LC-MS/MS method was reported for the quantification of vactosertib. To develop a validated LC-MS/MS method for the quantification of vactosertib in rat plasma, vactosertib and cabozantinib (internal standard [IS]) were detected using Waters LC-MS/MS system in MRM positive ionization mode, with a mixture of 0.2% formic acid and acetonitrile (70:30, v/v) on an Agilent XDB C18 (50 × 2.1 mm, 5 μm) column at a flow rate of 0.8 mL/min. The method was validated in accordance with M10 bioanalytical method validation USFDA guidelines and applied for the determination of pharmacokinetic parameters in rat plasma. The analytes were detected at m/z 400.23 → 289.19 and m/z 502.13 → 323.07 for vactosertib, and IS, respectively. The method demonstrated a sensitivity of 1.0 ng/mL, linearity ranging from 1.0 to 1000.0 ng/mL, an r2 of 0.999, accuracy ranged between 91.60% and 100.70%, and the drug was found to be stable across all freeze-thaw cycles. The results indicated that the method was selective, accurate, and validated for quantification of vactosertib in biological fluids and pharmacokinetic profiling of vactosertib.
Insights
A new LC-MS/MS method quantifies vactosertib in rat plasma, crucial for understanding its pharmacokinetics. This validated assay enables accurate drug monitoring in biological fluids.
Area of Science:
- Pharmacology and Toxicology
- Analytical Chemistry
- Bioanalysis
Background:
- Vactosertib, a transforming growth factor β-receptor type-1 (TGFBR1) inhibitor, is FDA-approved for cancer treatment.
- No validated LC-MS/MS method exists for vactosertib quantification in biological matrices.
- Accurate quantification is essential for pharmacokinetic profiling and therapeutic drug monitoring.
Purpose of the Study:
- Develop and validate a sensitive LC-MS/MS method for vactosertib quantification in rat plasma.
- Apply the validated method to determine vactosertib's pharmacokinetic parameters in rats.
- Establish a reliable bioanalytical tool for vactosertib research and clinical applications.
Main Methods:
- Vactosertib and cabozantinib (internal standard) were analyzed using a Waters LC-MS/MS system.
- Analysis employed MRM positive ionization mode with an Agilent XDB C18 column.
- Mobile phase consisted of formic acid and acetonitrile (70:30, v/v) at a flow rate of 0.8 mL/min.
Main Results:
- The method achieved a sensitivity of 1.0 ng/mL with linearity from 1.0 to 1000.0 ng/mL (r² = 0.999).
- Accuracy ranged from 91.60% to 100.70%, demonstrating high precision.
- Vactosertib stability was confirmed across all freeze-thaw cycles, indicating robustness.
Conclusions:
- A selective, accurate, and validated LC-MS/MS method for vactosertib quantification in rat plasma was successfully developed.
- The method is suitable for pharmacokinetic profiling and supports further research on vactosertib.
- This validated assay provides a critical tool for bioanalytical studies involving vactosertib.
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