Green Analytical Approach for HPLC Method Development for Quantification of Sorafenib and Its Pharmacopeia Impurities: LC–MS/MS Characterization and Toxicity Prediction of Stress Degradation Products
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引用次数: 0
Abstract
This research presents the development and validation of chromatographic method for analyzing sorafenib and its pharmacopeial impurities, with a focus on stability studies and degradation product (DP) characterization. Initial method optimization involved exploring various column and buffer combinations, ultimately achieving optimal separation and peak symmetry using an ODS‐AQ YMC (150 mm) column with 0.6 mL/min gradient flow of 10 mM ammonium formate buffer adjusted to pH 3.4 with formic acid as solvent A, and ethanol as solvent B as mobile phase and 246 nm wavelength. Method exhibits calibration curve linear in 50–300 µg/mL for sorafenib and 0.050–0.30 µg/mL for impurities with a detection limit of 0.015 µg/mL for impurities. A structural elucidation of DPs was performed using LC–MS/MS, providing valuable insights into their molecular compositions, and was characterized as 4‐[4‐(carboxyamino)phenoxy]pyridine‐2‐carboxylic acid (DP 1) and 4‐(4‐aminophenoxy)pyridine‐2‐carboxamide (DP 2). Using AGREE and GAPI metrics, evaluation highlighted method sustainability through ethanol–water solvents and shorter column to reduce energy consumption. Toxicity assessments revealed differences in environmental impact and toxicological profiles of DPs, emphasizing importance of managing safety considerations for sorafenib and its DPs. This research offers novel insights into sorafenib analysis by addressing pharmacopeial impurities, characterizing DPs, and evaluating method sustainability and safety.
期刊介绍:
Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance.
Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.