Liquid chromatography and mass spectrometric studies of gilteritinib fumarate and characterization of its major degradation products by NMR†

IF 2.7 3区 化学 Q2 CHEMISTRY, ANALYTICAL
Bhuvaneshwari Vuyyala, Krishna Prasad Pisini and Debasish Swain
{"title":"Liquid chromatography and mass spectrometric studies of gilteritinib fumarate and characterization of its major degradation products by NMR†","authors":"Bhuvaneshwari Vuyyala, Krishna Prasad Pisini and Debasish Swain","doi":"10.1039/D4AY01094A","DOIUrl":null,"url":null,"abstract":"<p >Gilteritinib fumarate (GTB) is an anti-cancer drug belonging to the class of tyrosine kinase inhibitors used for the treatment of acute myeloid leukemia. It has been designated as an orphan drug by the US Food and Drug Administration (US FDA). The present research focused on carrying out the forced degradation studies of GTB and developing a UHPLC-PDA stability indicating method capable of separating GTB and its degradation products. The degradation studies were carried out under hydrolytic (acid, base, and neutral), oxidative, thermal, and light conditions. The drug degraded under hydrolytic and oxidative conditions whereas it was found to be stable under thermal and light exposure. The separation of the components was achieved on an Acquity BEH C18 column (2.1 × 100 mm; 1.7<em>μ</em>) and a mobile phase comprising ammonium acetate and acetonitrile eluting in gradient mode at a flow rate of 0.3 mL min<small><sup>−1</sup></small>. A total of five degradation products were obtained and were structurally characterized with the help of accurate mass and tandem mass experiments performed on LC-QTOF-MS equipment and DP-1 was isolated and characterized using 1D and 2D NMR experiments. The UHPLC-PDA method was validated as per the ICH Q2 (R1) guidelines for its accuracy, precision, linearity, and specificity. The method was found to be appropriate for its intended purpose and can be effectively used in the determination of GTB and its degradation products and/or impurities in bulk drugs as well as formulations.</p>","PeriodicalId":64,"journal":{"name":"Analytical Methods","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Analytical Methods","FirstCategoryId":"92","ListUrlMain":"https://pubs.rsc.org/en/content/articlelanding/2024/ay/d4ay01094a","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, ANALYTICAL","Score":null,"Total":0}
引用次数: 0

Abstract

Gilteritinib fumarate (GTB) is an anti-cancer drug belonging to the class of tyrosine kinase inhibitors used for the treatment of acute myeloid leukemia. It has been designated as an orphan drug by the US Food and Drug Administration (US FDA). The present research focused on carrying out the forced degradation studies of GTB and developing a UHPLC-PDA stability indicating method capable of separating GTB and its degradation products. The degradation studies were carried out under hydrolytic (acid, base, and neutral), oxidative, thermal, and light conditions. The drug degraded under hydrolytic and oxidative conditions whereas it was found to be stable under thermal and light exposure. The separation of the components was achieved on an Acquity BEH C18 column (2.1 × 100 mm; 1.7μ) and a mobile phase comprising ammonium acetate and acetonitrile eluting in gradient mode at a flow rate of 0.3 mL min−1. A total of five degradation products were obtained and were structurally characterized with the help of accurate mass and tandem mass experiments performed on LC-QTOF-MS equipment and DP-1 was isolated and characterized using 1D and 2D NMR experiments. The UHPLC-PDA method was validated as per the ICH Q2 (R1) guidelines for its accuracy, precision, linearity, and specificity. The method was found to be appropriate for its intended purpose and can be effectively used in the determination of GTB and its degradation products and/or impurities in bulk drugs as well as formulations.

Abstract Image

Abstract Image

富马酸吉特替尼的液相色谱和质谱研究及其主要降解产物的核磁共振表征
富马酸吉特替尼(GTB)是一种抗癌药物,属于酪氨酸激酶抑制剂类,用于治疗急性髓性白血病。它已被美国食品和药物管理局(US FDA)指定为孤儿药。本研究的重点是对 GTB 进行强制降解研究,并开发一种能够分离 GTB 及其降解产物的超高效液相色谱-PDA 稳定性指示方法。降解研究是在水解(酸、碱和中性)、氧化、热和光照条件下进行的。药物在水解和氧化条件下降解,而在热和光照条件下则保持稳定。采用 Acquity BEH C18 色谱柱(2.1 × 100 mm;1.7μ)和乙酸铵与乙腈组成的流动相,以 0.3 mL/min-1 的流速进行梯度洗脱,实现了药物成分的分离。在 LC-QTOF-MS 设备上进行了精确的质量和串联质量实验,共获得了五种降解产物并对其结构进行了表征,同时利用一维和二维核磁共振实验分离和表征了 DP-1。根据 ICH Q2 (R1) 指南,对 UHPLC-PDA 方法的准确度、精密度、线性度和特异性进行了验证。结果表明,该方法符合预期目的,可有效测定散装药物和制剂中的 GTB 及其降解产物和/或杂质。
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
Analytical Methods
Analytical Methods CHEMISTRY, ANALYTICAL-FOOD SCIENCE & TECHNOLOGY
CiteScore
5.10
自引率
3.20%
发文量
569
审稿时长
1.8 months
期刊介绍: Early applied demonstrations of new analytical methods with clear societal impact
×
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