Novel degradation products of argatroban: Isolation, synthesis and extensive characterization using NMR and LC-PDA-MS/Q-TOF  

作　　者：Vinodh Guvvala Venkatesan Chidambaram Subramanian Jaya Shree Anireddy Mahesh Konda 

机构地区：[1]Centre for Chemical Science&Technology, Institute of Science& Technology, JNTUH [2]Gland Pharma Ltd., Research and Development, D.P.Pally

出　　处：《Journal of Pharmaceutical Analysis》2018年第2期86-95,共10页药物分析学报（英文版）

摘　　要：Forced degradation study of argatroban under conditions of hydrolysis(neutral, acidic and alkaline), oxidation,photolysis and thermal stress, as suggested in the ICH Q1 A(R2), was accomplished. The drug showed significant degradation under hydrolysis(acidic, alkaline) and oxidation(peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products(DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by ~1H NMR,^(13)C NMR, 2 D NMR, Q-TOF-MSnand IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.Forced degradation study of argatroban under conditions of hydrolysis(neutral, acidic and alkaline), oxidation,photolysis and thermal stress, as suggested in the ICH Q1A(R2), was accomplished. The drug showed significant degradation under hydrolysis(acidic, alkaline) and oxidation(peroxide stress) conditions. The drug remained stable under thermal and photolytic stress conditions. In total, seven novel degradation products(DP-1 to DP-7) were found under diverse conditions, which were not reported earlier. The chemical structures of these degradation products were characterized by ~1H NMR,^(13)C NMR, 2D NMR, Q-TOF-MSnand IR spectral analysis and the proposed degradation products structures were further confirmed by the individual synthesis.

关 键 词：ARGATROBAN FORCED degradation NMR LC-PDA LC-MS/Q-TOF-MSn 

分 类 号：R[医药卫生]