{"title":"Estimation of protein aggregates in Darbepoetin alfa formulations by developing a single validated analytical method","authors":"Nupur Garg, Sanjay Mendiratta, Gurminder Bindra, Sakshi Gehlot, Krutika Goswami, Charu Mehra Kamal","doi":"10.1016/j.jchromb.2025.124518","DOIUrl":null,"url":null,"abstract":"<div><div>Darbepoetin alfa is a new generation recombinant human erythropoiesis stimulating agent having extended half-life as compared to recombinant human erythropoietin. It is given as a life-saving drug for anemic disorders caused by chronic kidney diseases, cancer, etc. With the presence of commercial formulations of darbepoetin biosimilars in the market and non-availability of any established method in literature or testing guidelines in any compendia for their purity and quality, this research aims to develop a sensitive and robust method to determine the aggregate impurities by using size exclusion chromatographic technique. The method was optimized for sharp and high-resolution monomer peak of darbepoetin and other interferences which was further validated according to ICH Q2(R2) guidelines. The developed method was further tested on the commercial samples to verify the same. Additionally, stress testing of samples was done to simulate the after-production exposure and stability assessment. The results demonstrated that the method for analysing aggregates in darbepoetin is complying the criteria of being sensitive, specific, accurate, robust and reliable.</div></div>","PeriodicalId":348,"journal":{"name":"Journal of Chromatography B","volume":"1254 ","pages":"Article 124518"},"PeriodicalIF":2.8000,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Chromatography B","FirstCategoryId":"1","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1570023225000704","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Darbepoetin alfa is a new generation recombinant human erythropoiesis stimulating agent having extended half-life as compared to recombinant human erythropoietin. It is given as a life-saving drug for anemic disorders caused by chronic kidney diseases, cancer, etc. With the presence of commercial formulations of darbepoetin biosimilars in the market and non-availability of any established method in literature or testing guidelines in any compendia for their purity and quality, this research aims to develop a sensitive and robust method to determine the aggregate impurities by using size exclusion chromatographic technique. The method was optimized for sharp and high-resolution monomer peak of darbepoetin and other interferences which was further validated according to ICH Q2(R2) guidelines. The developed method was further tested on the commercial samples to verify the same. Additionally, stress testing of samples was done to simulate the after-production exposure and stability assessment. The results demonstrated that the method for analysing aggregates in darbepoetin is complying the criteria of being sensitive, specific, accurate, robust and reliable.
期刊介绍：
The Journal of Chromatography B publishes papers on developments in separation science relevant to biology and biomedical research including both fundamental advances and applications. Analytical techniques which may be considered include the various facets of chromatography, electrophoresis and related methods, affinity and immunoaffinity-based methodologies, hyphenated and other multi-dimensional techniques, and microanalytical approaches. The journal also considers articles reporting developments in sample preparation, detection techniques including mass spectrometry, and data handling and analysis.
Developments related to preparative separations for the isolation and purification of components of biological systems may be published, including chromatographic and electrophoretic methods, affinity separations, field flow fractionation and other preparative approaches.
Applications to the analysis of biological systems and samples will be considered when the analytical science contains a significant element of novelty, e.g. a new approach to the separation of a compound, novel combination of analytical techniques, or significantly improved analytical performance.
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