Quantification of venadaparib, a novel PARP inhibitor, in the rat and dog plasma using liquid chromatography/tandem mass spectrometry

Abstract

AbstractVenadaparib (VEN), a next-generation inhibitor of poly (ADP-ribose) polymerases, is under development for oral use in patients having cancers with deoxyribonucleic acid repair defects. The objective of this study was to develop and validate a sensitive and robust analytical method for quantifying VEN in a small volume of plasma samples from rats and dogs, and to assess the feasibility of the assay for application in pharmacokinetic/toxicokinetic studies. Plasma samples were subjected to deproteination, and an aliquot was injected into an LC–MS/MS system. VEN and imipramine were analyzed in the positive ion mode and quantified by monitoring the transition at m/z 407.2 → 70.0 for VEN and 281.2 → 86.1 for imipramine. The lower and upper limits of the assay were determined to be 1 and 1000 ng/mL, respectively, with acceptable linearity (r2 > 0.995). Validation parameters, such as accuracy, precision, dilution, recovery, matrix effect, and stability, were within acceptable ranges. This method was adequately applied to the characterization of pharmacokinetics of VEN in rats and dogs at the oral dose of 30 and 0.5 mg/kg, respectively. These findings suggest that the validated assay is applicable to the kinetic studies of VEN with a small volume of plasma samples from the animals.