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 1.25-2000ng/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 (1.25ng/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.
Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Universiteitsweg 99, 3584 CG Utrecht, The Netherlands. Electronic address: R.W.Sparidans@uu.nl.
Rolf W
RW
Sparidans
Selvi
S
Durmus
Alfred H
AH
Schinkel
Jan H M
JH
Schellens
Jos H
JH
Beijnen
D000097:Acetonitriles / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D002138:Calibration; D002853:Chromatography, Liquid; D004492:Edetic Acid / Q000737:chemistry; D005260:Female; D000077156:Gefitinib; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D051379:Mice; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D011786:Quality Control; D011799:Quinazolines / Q000737:chemistry; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
D000097:Acetonitriles; D007211:Indoles; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C531549:rucaparib; D004492:Edetic Acid; D000077156:Gefitinib; C032159:acetonitrile
AUC; LC–MS/MS; LLOQ; PARP; PARP inhibitor; Plasma; QC; Rucaparib; SRM; T(1/2); area under the plasma concentration-time curve; elimination half-life; lower limit of quantification; poly(ADP-ribose) polymerase; quality control; selected reaction monitoring