抗凝药物利伐沙班手性杂质的合成与表征

Prashant A. Patil, Sneha N. Tambat, Dilip R. Birari, Pritesh B. Kardile
{"title":"抗凝药物利伐沙班手性杂质的合成与表征","authors":"Prashant A. Patil, Sneha N. Tambat, Dilip R. Birari, Pritesh B. Kardile","doi":"10.47392/irjaem.2024.0322","DOIUrl":null,"url":null,"abstract":"The mechanism of action of the anticoagulant medication rivaroxaban is the direct and specific suppression of activated coagulation factor X (FXa). With just (S)-Rivaroxaban exhibiting pharmacological activity and (R)-Rivaroxaban being an impurity that must be controlled, this molecule only has one chiral centre. The present work describes the synthesis of chiral impurities of each intermediate, including KSM and its drug substance, and their characterization by spectral data (IR, MS, 1H-NMR, and 13C-NMR). The chiral impurity of drug substance is challenging during the process development of Rivaroxaban, and it is challenging for all pharmaceutical industries as well. The opposite isomeric impurity is introduced form its key starting material and it follows the same reaction mechanism path up to final drug substance. This work will help quality control (QC) to identify and control these impurities in the Rivaroxban drug substance as per ICH guideline. ","PeriodicalId":517878,"journal":{"name":"International Research Journal on Advanced Engineering and Management (IRJAEM)","volume":"14 3","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and Characterization of Chiral Impurities of Rivaroxaban, Used as an Anticoagulant Drug\",\"authors\":\"Prashant A. Patil, Sneha N. Tambat, Dilip R. Birari, Pritesh B. Kardile\",\"doi\":\"10.47392/irjaem.2024.0322\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"The mechanism of action of the anticoagulant medication rivaroxaban is the direct and specific suppression of activated coagulation factor X (FXa). With just (S)-Rivaroxaban exhibiting pharmacological activity and (R)-Rivaroxaban being an impurity that must be controlled, this molecule only has one chiral centre. The present work describes the synthesis of chiral impurities of each intermediate, including KSM and its drug substance, and their characterization by spectral data (IR, MS, 1H-NMR, and 13C-NMR). The chiral impurity of drug substance is challenging during the process development of Rivaroxaban, and it is challenging for all pharmaceutical industries as well. The opposite isomeric impurity is introduced form its key starting material and it follows the same reaction mechanism path up to final drug substance. This work will help quality control (QC) to identify and control these impurities in the Rivaroxban drug substance as per ICH guideline. \",\"PeriodicalId\":517878,\"journal\":{\"name\":\"International Research Journal on Advanced Engineering and Management (IRJAEM)\",\"volume\":\"14 3\",\"pages\":\"\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2024-07-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Research Journal on Advanced Engineering and Management (IRJAEM)\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.47392/irjaem.2024.0322\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Research Journal on Advanced Engineering and Management (IRJAEM)","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.47392/irjaem.2024.0322","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

抗凝药物利伐沙班的作用机制是直接特异性抑制活化的凝血因子 X (FXa)。由于只有(S)-利伐沙班具有药理活性,而(R)-利伐沙班是必须控制的杂质,因此该分子只有一个手性中心。本研究介绍了包括 KSM 及其药物物质在内的每种中间体手性杂质的合成及其光谱数据(红外光谱、质谱、1H-NMR 和 13C-NMR)表征。药物的手性杂质是利伐沙班工艺开发过程中的一个难题,也是所有制药行业面临的一个难题。相反异构体杂质从其关键起始原料中引入,并遵循相同的反应机制路径直至最终药物。这项工作将有助于质量控制(QC)部门根据 ICH 指南识别和控制利伐沙班药物中的这些杂质。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Synthesis and Characterization of Chiral Impurities of Rivaroxaban, Used as an Anticoagulant Drug
The mechanism of action of the anticoagulant medication rivaroxaban is the direct and specific suppression of activated coagulation factor X (FXa). With just (S)-Rivaroxaban exhibiting pharmacological activity and (R)-Rivaroxaban being an impurity that must be controlled, this molecule only has one chiral centre. The present work describes the synthesis of chiral impurities of each intermediate, including KSM and its drug substance, and their characterization by spectral data (IR, MS, 1H-NMR, and 13C-NMR). The chiral impurity of drug substance is challenging during the process development of Rivaroxaban, and it is challenging for all pharmaceutical industries as well. The opposite isomeric impurity is introduced form its key starting material and it follows the same reaction mechanism path up to final drug substance. This work will help quality control (QC) to identify and control these impurities in the Rivaroxban drug substance as per ICH guideline. 
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
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:604180095
Book学术官方微信