Prashant A. Patil, Sneha N. Tambat, Dilip R. Birari, Pritesh B. Kardile
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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。
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.