Identification, Isolation and Characterization of Degradation Products (DPs) in Osimertinib Mesylate (OSM) Tablets by UHPLC-IMS-QTOF-MS, and NMR: Evaluation of Genotoxicity for OSM and DPs

Bhutnar, Arun D.; Saple, Seema R.; Vaidya, Vikas V.

doi:10.1080/22297928.2021.2017796

Cited by 1 publication

(1 citation statement)

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“…Evidently, the chemical structure of osimertinib mesylate involved indole ring, tertiary amine, amide, and ester bond. Bhutnar et al 9 studied osimertinib mesylate tablets stress testing and reported two pseudo-DPs in acidic and alkaline hydrolysis. Also same reported the three DPs in acidic hydrolysis viz., m/z 446, m/z 518, and m/z 473.…”

Section: Introductionmentioning

confidence: 99%

Insight into in silico prediction and chemical degradation study of osimertinib mesylate by LC-HRMS and NMR: Investigation of a typical case of alkaline pH-mediated oxidative degradation product

Dhiman

Chavan

Ramarapu

et al. 2023

Eur J Mass Spectrom (Chichester)

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Osimertinib mesylate is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor used to treat nonsmall-cell lung cancer. The objective was to understand in silico prediction and chemical-based stress testing of the osimertinib mesylate. A total of eight degradation products (DPs) were formed under chemical stress testing. An in silico tool viz., Zeneth predicted a higher percentage of DPs. The separation of all the DPs was achieved using reversed phase high-performance liquid chromatography, employing X-Bridge C18 column with ammonium acetate (pH adjusted to 7.50 with ammonia) and acetonitrile as mobile phase. The overall results showed it underwent significant degradation in acidic, alkaline, and oxidative conditions. In rest of the conditions, osimertinib mesylate was found to be stable or slight degradation was observed in photolytic condition. The structure of DPs was elucidated with a comparison of data generated from high-resolution mass spectrometry (HRMS) of osimertinib mesylate and its degradation products. To confirm the unambiguous regioisomers, one-dimensional (1D) and two-dimentional (2D) nuclear magnetic resonance studies were performed. Furthermore, the N-oxide position was assigned for the first time using the Meisenheimer rearrangement reaction in atmospheric pressure chemical ionization mode. Interestingly, an unusual reaction of DP2 formation was observed at alkaline conditions. In silico tools such as DEREK and Sarah predicted osimertinib mesylate and most of the DPs found to be structural alert for mutagenicity.

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Section: Introductionmentioning

confidence: 99%