Liquid chromatography–tandem mass spectrometric assay for the PARP inhibitor rucaparib in plasma

Abstract

A quantitative bioanalytical liquid chromatography–tandem mass spectrometric (LC–MS/MS) assay for the poly(ADP-ribose) polymerase-1 inhibitor rucaparib was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing gefitinib as internal standard. Diluted extract was directly injected into the reversed-phase chromatographic system. The eluate was transferred into the electrospray interface with positive ionization and the analyte was detected in the selected reaction monitoring mode of a triple quadrupole mass spectrometer.The assay was validated in a 1.25–2000ng/ml calibration range with r2=0.9958±0.0012 for linear regression with quadratic weighting (n=6). Within day precisions (n=18) were 2.0–5.4%, between day (3 days; n=18) precisions 3.2–8.0% and accuracies (n=18) were 89.7–93.2%. At the lower limit of quantification (1.25ng/ml) these parameters were 9.6%, 13.7% and 85.3%, respectively. The drug was sufficiently stable under all relevant analytical conditions. Finally, the assay was successfully used to determine drug pharmacokinetics in female FVB wild type mice.