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

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 1.25-2000 ng/ml calibration range with r(2) = 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 (1.25 ng/ml) these parameters were 9.6%, 13.7% and 853%, 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. (C) 2013 Elsevier B.V. All rights reserved.