LC-ESI-QTOF-MS analysis utilizing gas-phase fragmentation reactions subjected to ESI-IS-CID and ESI-CID-MS/MS conditions to study the degradation behaviour of sorafenib tosylate: NMR and in vitro cytotoxicity and apoptosis detection studies of hydrolytic degradation products

Publication date: Available online 10 September 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): P. Johnsirani, Aabid Abdullah Wani, Prasad V Bharatam, Satheeshkumar NanjappanAbstractThe present study was to investigate the degradation profile of sorafenib tosylate (SORA), a potent oral multi-kinase inhibitor under various stress conditions as per ICH (Q1A (R2)) guidelines. Separation of SORA and its degradation products (DP-1 to DP-5) was achieved on Acquity UPLC BEH C18 (100 mm x 2.1 mm x1.7 µm) column using a gradient elution of 0.1% formic acid and acetonitrile at a flow rate of 0.3 mL/min within 12 min. High resolution quadruple time-of-flight mass spectrometer (Q-TOF/MS) was utilized for characterization of all DPs. In ESI/CID-MS/MS experiments, the protonated DP-1 and DP-2 exhibited few interesting product ions which provide a compelling evidence for the compounds to undergo gas phase rearrangement reaction justified by its mechanistic explanation in support with density functional theory (DFT). In-source collision-induced dissociation (IS-CID) fragmentation using ESI/APCI-MS analysis exhibited the formation of N-deoxygenated product ion peak corresponds to pyridine N-oxide moiety as in DP-5. Further, major hydrolytic DPs (DP-2 and DP-3) were isolated on preparative HPLC and structural elucidation was done using ID NMR (1H, 13C and DEPT-135) experiments. In vitro cytotoxicity study for SORA and its isolated DPs were assessed by obs...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research