Forced Degradation Study of Zanubrutinib: An LC–PDA and LC–MS Approach

Abstract

Zanubrutinib is an unfamiliar second generation selective Brutson’s Tyrosine Kinase inhibitor used to treat mantle cell lymphoma. In the present analysis, a new, stability indicating reverse-phase, high performance liquid chromatography method was developed and validated for the determination of Zanubrutinib succeeding degradation studies as pert the International Conference on Harmonization guidelines. The chromatographic separation of Zanubrutinib was achieved in a C18 column (250 × 4.6 mm, 5-μm particle size) using a mobile phase of Acetonitrile: 0.1% Tri Ethyl Amine (65:35 v/v) monitored at 219 nm. The forced degradation studies were conducted by exposing the analyte to acidic, alkaline and neutral hydrolysis, oxidative, reductive, photolytic, and thermal stress conditions and the degradation behavior was studied. The analyte showed degradation under acidic, alkaline, oxidative and reductive stress conditions with additional peaks but, it was stable under neutral, photolytic and thermal stress conditions. The developed method was extended to triple quadruple mass spectrometry to characterize degradation products and to study the fragmentation pattern. Total four degradants were characterized including DP1 in acid &base hydrolysis, DP2 in oxidative and DP3, DP4 in reductive stress condition. As no substantial method was available for quantification of Zanubrutinib and to characterize zanubrutinib degradants, this method can be used for regular analysis in quality control labs.

Identification of degradation products of brivaracetam using liquid chromatography quadrupole time‐of‐flight tandem mass spectrometry: Degradation pathway elucidation

“…[18][19][20] Therefore, it is essential to identify degradation pathways when developing formulation strategies and stability-indicating methods. 21,22 However, there is currently no systematic study reported on the degradation pathway of brivaracetam, 23,24 highlighting the need for further investigation.…”

“…The resulting degradation products (DPs) have the potential to affect the safety and efficacy of drugs, possibly leading to adverse effects and toxicity 18–20 . Therefore, it is essential to identify degradation pathways when developing formulation strategies and stability‐indicating methods 21,22 . However, there is currently no systematic study reported on the degradation pathway of brivaracetam, 23,24 highlighting the need for further investigation.…”