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Abstract Venadaparib (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 (r 2 > 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.

A previous study proposed an optimal vibration isolator for self-excitation, but the solution results showed a critical drawback for the basement input. Because the plant system is exposed to self-excitation and basement input, the vibration isolator characteristics must meet all the requirements of both excitation cases. Two performance indices of the vibration isolator were introduced to evaluate the vibration control capability over two excitation cases, self-excitation and basement input, using the theoretical linear model of the electric power generator. The compromise strategy was devoted to enhancing the vibration control capability over the basement input, owing to the acceptable margin for self-excitation. The modification of the mechanical properties of the vibration isolator focused on the isolator between the mass block and the surrounding building. Simulation results revealed that an increase in the spring coefficient and a decrease in the damping coefficient of the vibration isolator beneath the mass block could enhance the vibration reduction capability over the basement input.