Identification and characterization of alkaline hydrolytic degradation products of ivacaftor by UPLC-PDA and UPLC-ESI-QTOF-MS techniques

IF 1.8 3区化学 Q4 BIOCHEMICAL RESEARCH METHODS Rapid Communications in Mass Spectrometry Pub Date : 2024-10-30 DOI:10.1002/rcm.9930

Aastha Bishnoi, Alka Bali, Akshay Kumar

{"title":"Identification and characterization of alkaline hydrolytic degradation products of ivacaftor by UPLC-PDA and UPLC-ESI-QTOF-MS techniques","authors":"Aastha Bishnoi, Alka Bali, Akshay Kumar","doi":"10.1002/rcm.9930","DOIUrl":null,"url":null,"abstract":"<div>\n \n <section>\n \n <h3> Rationale</h3>\n \n <p>The study of inherent stability characteristics of drugs has been advocated to be important by various regulatory agencies like the ICH, USFDA, and others. The current work was envisaged to investigate the forced degradation profile of the drug ivacaftor under ICH-prescribed stress conditions, identification of its potential degradants, and postulation of the degradation routes for their generation.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>The stress degradation studies were performed on the drug as per the ICH guideline Q1A(R2). A UPLC-photodiode array-based chromatographic method was developed to satisfactorily resolve the drug from its degradation products, validated in accordance with various ICH prescribed parameters, and assessed for its BAGI practicality index. The degradation products were identified and characterized by UPLC-ESI-QTOF-MS studies.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>The drug was found to significantly degrade under conditions of alkaline hydrolytic stress and it was found to be stable under all other stressor environments including acid/neutral hydrolytic, photolytic, thermal, and oxidative stress. Four alkaline hydrolytic degradation products (I-IV) were revealed by UPLC-QTOF-MS studies which were well-resolved from the drug over a C18 UPLC column by the developed UPLC-PDA method. The detection wavelength was selected as 310 nm. Characterization of the four degradation products (I–IV) was carried out by their mass spectral data and their respective degradation routes were elucidated.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>A UPLC-PDA method was developed and validated for ivacaftor and its practicality BAGI index was computed. Four alkaline hydrolytic degradation products of ivacaftor were revealed through UPLC-ESI-QTOF-MS studies and corresponding degradation routes were elucidated.</p>\n </section>\n </div>","PeriodicalId":225,"journal":{"name":"Rapid Communications in Mass Spectrometry","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Rapid Communications in Mass Spectrometry","FirstCategoryId":"92","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/rcm.9930","RegionNum":3,"RegionCategory":"化学","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

Rationale

The study of inherent stability characteristics of drugs has been advocated to be important by various regulatory agencies like the ICH, USFDA, and others. The current work was envisaged to investigate the forced degradation profile of the drug ivacaftor under ICH-prescribed stress conditions, identification of its potential degradants, and postulation of the degradation routes for their generation.

Methods

The stress degradation studies were performed on the drug as per the ICH guideline Q1A(R2). A UPLC-photodiode array-based chromatographic method was developed to satisfactorily resolve the drug from its degradation products, validated in accordance with various ICH prescribed parameters, and assessed for its BAGI practicality index. The degradation products were identified and characterized by UPLC-ESI-QTOF-MS studies.

Results

The drug was found to significantly degrade under conditions of alkaline hydrolytic stress and it was found to be stable under all other stressor environments including acid/neutral hydrolytic, photolytic, thermal, and oxidative stress. Four alkaline hydrolytic degradation products (I-IV) were revealed by UPLC-QTOF-MS studies which were well-resolved from the drug over a C18 UPLC column by the developed UPLC-PDA method. The detection wavelength was selected as 310 nm. Characterization of the four degradation products (I–IV) was carried out by their mass spectral data and their respective degradation routes were elucidated.

Conclusions

A UPLC-PDA method was developed and validated for ivacaftor and its practicality BAGI index was computed. Four alkaline hydrolytic degradation products of ivacaftor were revealed through UPLC-ESI-QTOF-MS studies and corresponding degradation routes were elucidated.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

利用 UPLC-PDA 和 UPLC-ESI-QTOF-MS 技术鉴定和表征伊伐卡夫多的碱性水解降解产物。

理由：ICH、USFDA 等多个监管机构都认为对药物内在稳定性特征的研究非常重要。目前的工作旨在研究药物 ivacaftor 在 ICH 规定的应力条件下的强制降解概况，确定其潜在降解物，并推测其产生的降解途径：方法：根据 ICH 指南 Q1A(R2)，对药物进行应力降解研究。开发了一种基于超高效液相色谱-光电二极管阵列的色谱法，可从降解产物中分辨出令人满意的药物，并根据 ICH 规定的各种参数进行了验证，还评估了其 BAGI 实用性指数。通过 UPLC-ESI-QTOF-MS 研究对降解产物进行了鉴定和表征：结果：发现该药物在碱性水解应力条件下降解明显，而在所有其他应力环境下，包括酸性/中性水解、光解、热应力和氧化应力，该药物均保持稳定。通过 UPLC-QTOF-MS 研究发现了四种碱性水解降解产物（I-IV），采用所开发的 UPLC-PDA 方法，这些产物在 C18 UPLC 柱上能很好地从药物中分离出来。检测波长选为 310 nm。通过质谱数据对四种降解产物（I-IV）进行了表征，并阐明了它们各自的降解途径：建立并验证了伊伐卡夫多的UPLC-PDA方法，并计算了其实用性BAGI指数。通过UPLC-ESI-QTOF-MS研究发现了伊伐卡夫多的四种碱性水解降解产物，并阐明了相应的降解途径。

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分钟内获得全文去求助

来源期刊

Rapid Communications in Mass Spectrometry 化学-分析化学

CiteScore

4.10

自引率

5.00%

发文量

219

审稿时长

2.6 months

期刊介绍： Rapid Communications in Mass Spectrometry is a journal whose aim is the rapid publication of original research results and ideas on all aspects of the science of gas-phase ions; it covers all the associated scientific disciplines. There is no formal limit on paper length ("rapid" is not synonymous with "brief"), but papers should be of a length that is commensurate with the importance and complexity of the results being reported. Contributions may be theoretical or practical in nature; they may deal with methods, techniques and applications, or with the interpretation of results; they may cover any area in science that depends directly on measurements made upon gaseous ions or that is associated with such measurements.