Identification, Synthesis, and Strategy for Minimization of Potential Impurities in the Preclinical Anti-HBV Drug Y101

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• 作者：Zhanxing Hu ; Qiao An ; Kunfeng Li ; Yangong Zhang ; Jingying Qiu ; Bixue Xu ; Weidong Pan ; Peixue Cao ; Changxiao Liu ; Zhengming Huang ; Wen Xia ; Guangyi Liang
• 刊名：Organic Process Research & Development
• 出版年：2013
• 出版时间：September 20, 2013
• 年：2013
• 卷：17
• 期：9
• 页码：1156-1167
• 全文大小：568K
• 年卷期：v.17,no.9(September 20, 2013)
• ISSN：1520-586X

文摘

The identification of actual, potential, and theoretical impurities of N-[N-benzoyl-O-(2-dimethylaminoethyl)-l-tyrosyl]-l-phenylalaninol (Y101), a preclinical anti-HBV drug, is described in this article. The impurities were monitored by HPLC, and their structures were established on the basis of NMR, IR, and MS. Most of the impurities were synthesized, and their assigned constitutions were confirmed by HPLC co-injection with an ordinary column (Phenomenex Gemini, 250 mm 脳 4.6 mm, 5 渭m) or a chiral column (DAICEL Chiralcel OD-H). According to the synthetic route, the origins of all of these related impurities were analyzed, and some practical strategies were applied for minimizing these impurities to the level accepted by the International Conference on Harmonization (ICH), and therefore, these strategies can be well applied to the quality control in Y101 clinical sample manufacture.