Quality by Design Based Chromatography Technique Development and Validation for the Medicine Venetoclax (for Chronic Leukemia), in the Context of Impurities Including Degradation Products

IF 1.8 4区 医学 Q4 BIOCHEMICAL RESEARCH METHODS
Rajeshwari Dandabattina, Karuna Sree Merugu, Lova Gani Raju Bandaru, Haridasyam Sharathbabu, Rambabu Gundla, Naresh Kumar Katari
{"title":"Quality by Design Based Chromatography Technique Development and Validation for the Medicine Venetoclax (for Chronic Leukemia), in the Context of Impurities Including Degradation Products","authors":"Rajeshwari Dandabattina,&nbsp;Karuna Sree Merugu,&nbsp;Lova Gani Raju Bandaru,&nbsp;Haridasyam Sharathbabu,&nbsp;Rambabu Gundla,&nbsp;Naresh Kumar Katari","doi":"10.1002/bmc.70072","DOIUrl":null,"url":null,"abstract":"<p>The present research study describes the Venetoclax (VEN)-related substances test method using RP-HPLC/DAD techniques. It was developed and validated according to ICH Q14 and Q2(R2) guidelines. The substances were separated using an X-Bridge Phenyl column (150 mm × 4.6 mm, 3.5 μm) and a gradient program. The mobile phase A, consist 0.02 mM Na2HPO4 (pH 8.0) buffer and acetonitrile in an 80:20 v/v ratio. Mobile phase B was prepared using a 75:25 v/v mixture of acetonitrile and a pH 8.0 buffer and well mixed. The flow rate remains constant at 1.0 mL/min, traversing an appropriate gradient program. The VEN and its impurities were detected at 280 nm, with an injection volume of 15 μL and a runtime of 130 min. Moreover, we identified proper degradation impurities and sensitivity of VEN due to forced-degradation study experiments. The linearity and range of the testing procedure were validated by computing <i>r</i><sup>2</sup> values over 0.999. All organic impurities were recovered at a rate of 97.6%–106.0% with a relative standard deviation of 0.11%–4.35%. A robustness test was conducted utilizing the AQbD methodology. The proposed method was stability-indicating in nature and can be used for commercial samples in the pharmaceutical industries.</p>","PeriodicalId":8861,"journal":{"name":"Biomedical Chromatography","volume":"39 5","pages":""},"PeriodicalIF":1.8000,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/bmc.70072","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Chromatography","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/bmc.70072","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0

Abstract

The present research study describes the Venetoclax (VEN)-related substances test method using RP-HPLC/DAD techniques. It was developed and validated according to ICH Q14 and Q2(R2) guidelines. The substances were separated using an X-Bridge Phenyl column (150 mm × 4.6 mm, 3.5 μm) and a gradient program. The mobile phase A, consist 0.02 mM Na2HPO4 (pH 8.0) buffer and acetonitrile in an 80:20 v/v ratio. Mobile phase B was prepared using a 75:25 v/v mixture of acetonitrile and a pH 8.0 buffer and well mixed. The flow rate remains constant at 1.0 mL/min, traversing an appropriate gradient program. The VEN and its impurities were detected at 280 nm, with an injection volume of 15 μL and a runtime of 130 min. Moreover, we identified proper degradation impurities and sensitivity of VEN due to forced-degradation study experiments. The linearity and range of the testing procedure were validated by computing r2 values over 0.999. All organic impurities were recovered at a rate of 97.6%–106.0% with a relative standard deviation of 0.11%–4.35%. A robustness test was conducted utilizing the AQbD methodology. The proposed method was stability-indicating in nature and can be used for commercial samples in the pharmaceutical industries.

Abstract Image

在杂质包括降解产物的背景下,基于设计的质量色谱技术开发和验证药物Venetoclax(用于慢性白血病)
本研究介绍了利用反相高效液相色谱/DAD技术测定维妥克乐(ventoclax, VEN)相关物质的方法。根据ICH Q14和Q2(R2)指南进行开发和验证。采用X-Bridge苯基柱(150 mm × 4.6 mm, 3.5 μm)和梯度程序分离物质。流动相A由0.02 mM Na2HPO4 (pH 8.0)缓冲液和乙腈组成,比例为80:20 v/v。以75:25 v/v的乙腈和pH 8.0的缓冲液混合制备流动相B。流速保持在1.0 mL/min恒定,通过适当的梯度程序。在280 nm处检测VEN及其杂质,进样量为15 μL,运行时间为130 min。此外,我们通过强制降解研究实验确定了合适的降解杂质和VEN的敏感性。通过计算r2值大于0.999,验证了检测方法的线性度和范围。有机杂质回收率为97.6% ~ 106.0%,相对标准偏差为0.11% ~ 4.35%。采用AQbD方法进行稳健性检验。该方法具有稳定性指示性质,可用于制药工业的商业样品。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Biomedical Chromatography
Biomedical Chromatography 生物-分析化学
CiteScore
3.60
自引率
5.60%
发文量
268
审稿时长
2.3 months
期刊介绍: Biomedical Chromatography is devoted to the publication of original papers on the applications of chromatography and allied techniques in the biological and medical sciences. Research papers and review articles cover the methods and techniques relevant to the separation, identification and determination of substances in biochemistry, biotechnology, molecular biology, cell biology, clinical chemistry, pharmacology and related disciplines. These include the analysis of body fluids, cells and tissues, purification of biologically important compounds, pharmaco-kinetics and sequencing methods using HPLC, GC, HPLC-MS, TLC, paper chromatography, affinity chromatography, gel filtration, electrophoresis and related techniques.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信