Quantitative Determination of the PARP Inhibitor Olaparib (AZD 2281) in Rat Plasma using LC-MS/MS: Application to Pharmacokinetic Studies

Abstract

Purpose: Olaparib, a highly selective PARP inhibitor in advanced treatment of ovarian cancer. The method describes a simple, rapid, sensitive, specific LC-ESI-MS/MS assay for the simultaneous detection and accurate measurement of olaparib in rat plasma using telmisartan as an internal standard as per the regulatory guidelines. Methods: Chromatographic separation was carried out on a Liquid Chromatography with tandem mass spectrometry (LC-MS/MS) unit with a Kinetex EVO C18 column (50 × 4.6 mm, 5 µ) using a gradient mobile phase of acetonitrile and 5mM ammonium acetate in water. No endogenous interfering compounds were discovered at the retention time of olaparib (1.66 min) and telmisartan (IS, 1.77 min). Results: The MS/MS detection was performed in positive mode and MRM transitions were m/z 435.22→366.96 and 515.21→276.16 for olaparib and IS, respectively. This method was assessed to be stable, selective and no matrix effect in three concentrations (4, 500, 800 ng/mL). The intra and inter-day precisions were less than 7.55 % and accuracy ranged from 98.00 % to 106.38 %. The extraction recovery was within acceptable limits. Additionally, the method had good linearity in the range of 1-1000 ng/mL. Conclusion: The validated method was successfully applied to the pharmacokinetic study of rats through oral and intravenous administration routes.