Quantification of Vactosertib an Inhibitor of TGFBR1 by LC–MS/MS in Rat Plasma and Its Pharmacokinetic Profiling

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.