Isolation and identification of forced degradation products of Febuxostat

IF 17.7 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-02-20 DOI:10.1002/sscp.202300237

Rajesh Kanagaddi, Vaishnavi Chintala, S. Nannapaneni, N. K. Katari, Suresh Salakolusu, Jnsrc Murty, M. Ranga, Muralidharan Kaliyaperumal

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Abstract

The current study explains the degradation behavior of Febuxostat API, a non‐purine xanthine oxidase inhibitor used to treat hyperuricemia. A degradation study was carried out as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines, and the study confirms that the Febuxostat is largely stable in thermal, photolytic, oxidative, and basic hydrolytic conditions and labile in acid hydrolysis conditions. There were four different degradation products (DPs) found during acid hydrolysis; of these, DPs 2, 3, and 4 are new and have never been reported before, while DP 1 is known and has already been published. All these DPs were identified using ultra‐high‐performance liquid chromatography‐mass spectrometry (UHPLC‐MS) analysis, purified by using preparative HPLC, and characterized using high‐resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy techniques. The formed DPs are by the hydrolysis of the cyano functional group of Febuxostat and the esterification of DP‐1 under acidic conditions. All DP's structural characterization was carried out using NMR spectroscopy and HRMS. The present study describes concrete confirmation of DP structures and it explains the stability behavior of the Febuxostat. The current method is also used to identify DPs with shorter runtime in the future.

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非布索坦强制降解产物的分离与鉴定

本研究解释了非布司他原料药的降解行为，这是一种用于治疗高尿酸血症的非嘌呤黄嘌呤氧化酶抑制剂。研究证实，非布司他在热解、光解、氧化和碱性水解条件下基本稳定，而在酸性水解条件下则易变。在酸水解过程中发现了四种不同的降解产物（DPs）；其中，DPs 2、3 和 4 是新的降解产物，以前从未报道过，而 DP 1 是已知的降解产物，已经发表过。利用超高效液相色谱-质谱（UHPLC-MS）分析鉴定了所有这些 DPs，并利用制备型高效液相色谱进行了纯化，还利用高分辨率质谱（HRMS）和核磁共振（NMR）光谱技术对其进行了表征。DPs 是在酸性条件下通过水解非布索坦的氰基官能团和酯化 DP-1 而形成的。所有 DP 的结构表征都是通过核磁共振光谱和 HRMS 进行的。本研究描述了 DP 结构的具体确认，并解释了非布索坦的稳定性。目前的方法还可用于鉴定未来运行时间更短的 DP。

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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.