Validated stability indicating assay method of olaparib: LC-ESI-Q-TOF-MS/MS and NMR studies for characterization of its new hydrolytic and oxidative forced degradation products

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HIGHLIGHTSOlaperib is used to treat prostate, ovarian and breast cancer in the patients with hereditary BRCA1 and BRCA2 mutations.This is the first report on stability indicating assay method for olaperib according to ICH guidelines.Four new degradation products (DPs) were identified and characterized by using LC–ESI- QTOF-MS/MS.Major DPs (DP-1 and DP-2) were isolated and their chemical structures were confirmed by NMR experiments.Olaparib (OLA) is a poly ADP ribose polymerase (PARP) enzyme inhibitor used to treat prostate, ovarian and breast cancer. The drug substance OLA was subjected to forced degradation as per ICH prescribed guidelines. It was degraded in hydrolytic (acidic and basic) and oxidative stress conditions and yielded four degradation products (DPs) while it remained stable in neutral hydrolytic, dry heat and photolytic stress conditions. A stability indicating assay method was developed to separate OLA and its DPs using InertSustain C18 column (250 × 4.6 mm, 5 μm) with a gradient mobile phase of 10 mM ammonium acetate (pH 4.5) and acetonitrile (ACN) at a flow rate of 1mLmin−1. The characterization of DPs was carried out by using liquid chromatography-electrospray ionization-quadrupole-time of flight tandem mass spectrometry (LC-ESI-Q-TOF-MS/MS). Major degradation products (DP-1 and DP-2) were isolated by using preparative HPLC and structures were further confirmed by using NMR spectroscopy. All the obtained DPs were new and not reported previously. The developed chromatographic method was validated as per ICH Q2 (R1) guideline and USP general chapter on method validation.

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