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

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 r 2 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.