Establishment and validation of an innovative UPLC-MS/MS approach for quantitation and pharmacokinetics of veliparib in rat plasma

In this investigation, a rapid and reliable ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technique was developed for quantification of veliparib in rat plasma and used the method to study the pharmacokinetics and bioavailability of veliparib in rats after oral (6 mg kg(-1)) and intravenous (2 mg kg(-1)) administration. Plasma samples were protein precipitated with acetonitrile using midazolam as internal standard. A UPLC HSS T3 chromatographic column was utilized for separation, with a mobile phase consisting of methanol-water-formic acid in gradient elution procedure. Quantitative analysis was performed using multiple reaction monitoring in electrospray positive-ion mode. Veliparib exhibited excellent linearity within the 1-1,000 ng mL(-1) range (r > 0.99). The intra- and inter-day precision of veliparib were both within 15%, and the accuracy ranged from 93.7 to 107.7%. The average recovery was above 86%, and the matrix effect was 89.0-95.8%. The AUC((0-t)) values for oral and intravenous administration were 1014.7 +/- 42.9 and 647.2 +/- 85.2 h ng mL(-1), respectively, resulting in a bioavailability of 52.3%. The UPLC-MS/MS method established in this study featured a low sample injection volume, a low quantification limit, a short chromatographic runtime, high sensitivity, and selectivity. The developed method can be used for the pharmacokinetic analysis of veliparib in both preclinical and clinical studies.