Identification and structural characterization of potential degradation products of baricitinib using liquid chromatography combined with quadrupole time-of-flight mass spectrometry

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-04-12 DOI:10.1556/1326.2024.01212

Eleni Kakouri, Konstantinos Gkountanas, C. Kanakis, P. Tarantilis, Y. Dotsikas

{"title":"Identification and structural characterization of potential degradation products of baricitinib using liquid chromatography combined with quadrupole time-of-flight mass spectrometry","authors":"Eleni Kakouri, Konstantinos Gkountanas, C. Kanakis, P. Tarantilis, Y. Dotsikas","doi":"10.1556/1326.2024.01212","DOIUrl":null,"url":null,"abstract":"Baricitinib (BRT) is a drug substance with potent anti-inflammatory activity indicated in rheumatoid arthritis, atopic dermatitis, severe alopecia areata and recently for the treatment of Covid-19. Process impurities of the drug during its formulation are quite known, however studies regarding its degradation products (DPs) under stress conditions are limited. In this study, the drug was subjected to forced degradation under various degradation conditions, including acidic hydrolysis, alkaline hydrolysis, oxidative and thermal, to determine its inherent stability. To this purpose, a novel HPLC method was developed for the determination of degradation impurities of BRT. Alkaline hydrolysis test showed a selectivity towards breaking C–C bonds. This resulted to five DPs formed by chain scission reactions occurred at the pyrrolo-pyrimidine group between C6–C10 and C8–C9. Also, the ethylsulfonyl-azetidin-ylidene group was subjected to C–C bond cleavage at C12–C15 and C16–C18. Degradation products were further characterized with the use of liquid chromatography quadrupole time of flight tandem mass spectrometry (LC-Q-TOF-MS/MS).","PeriodicalId":1,"journal":{"name":"Accounts of Chemical Research","volume":null,"pages":null},"PeriodicalIF":16.4000,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Accounts of Chemical Research","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1556/1326.2024.01212","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}

引用次数: 0

Abstract

Baricitinib (BRT) is a drug substance with potent anti-inflammatory activity indicated in rheumatoid arthritis, atopic dermatitis, severe alopecia areata and recently for the treatment of Covid-19. Process impurities of the drug during its formulation are quite known, however studies regarding its degradation products (DPs) under stress conditions are limited. In this study, the drug was subjected to forced degradation under various degradation conditions, including acidic hydrolysis, alkaline hydrolysis, oxidative and thermal, to determine its inherent stability. To this purpose, a novel HPLC method was developed for the determination of degradation impurities of BRT. Alkaline hydrolysis test showed a selectivity towards breaking C–C bonds. This resulted to five DPs formed by chain scission reactions occurred at the pyrrolo-pyrimidine group between C6–C10 and C8–C9. Also, the ethylsulfonyl-azetidin-ylidene group was subjected to C–C bond cleavage at C12–C15 and C16–C18. Degradation products were further characterized with the use of liquid chromatography quadrupole time of flight tandem mass spectrometry (LC-Q-TOF-MS/MS).

查看原文本刊更多论文

利用液相色谱法结合四极杆飞行时间质谱法鉴定巴利替尼的潜在降解产物并确定其结构特征

巴利替尼（BRT）是一种具有强效抗炎活性的药物，适用于类风湿性关节炎、特应性皮炎、严重脱发，最近还被用于治疗 Covid-19。众所周知，该药物在配制过程中会产生杂质，但有关其在压力条件下的降解产物（DPs）的研究却十分有限。在本研究中，药物在各种降解条件下（包括酸性水解、碱性水解、氧化和热降解）被强制降解，以确定其固有的稳定性。为此，研究人员开发了一种新型高效液相色谱法，用于测定 BRT 的降解杂质。碱性水解测试表明，BRT 对 C-C 键的断裂具有选择性。这导致 C6-C10 和 C8-C9 之间的吡咯嘧啶基发生链断裂反应，形成五个 DPs。此外，乙砜基氮杂环丁烯基在 C12-C15 和 C16-C18 处也发生了 C-C 键断裂。利用液相色谱四极杆飞行时间串联质谱法（LC-Q-TOF-MS/MS）对降解产物进行了进一步鉴定。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

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.