非布司他副反应及降解杂质的分离和鉴定

发布时间：2018-01-21 06:21

本文关键词： XOR酶抑制剂非布司他有关物质副反应杂质降解产物杂质鉴定液相色谱-质谱联用核磁共振红外光谱　出处：《药物分析杂志》2015年03期 　论文类型：期刊论文

【摘要】：目的:分离和鉴定非布司他的副反应及降解有关物质。方法:采用LC-MS技术对非布司他原料中的3个杂质进行了鉴定,色谱柱为Diamonsil C18(200 mm×4.6 mm,5μm),流动相为甲醇-0.1%醋酸(60∶40),流速1.0 m L·min-1;利用制备高效液相色谱从非布司他原料中分离制备了其中2个杂质,并进一步采用红外光谱及核磁共振技术进行结构确证。结果:推测副反应产物为2-(3-((羟基亚胺)甲基)-4-异丁氧苯基)-4-甲基噻唑-5-羧酸和5-(5-(乙氧羰基)-4-甲基噻唑-2-基)-2-异丁氧苯甲酸,主要降解产物为2-(3-氨甲酰基-4-异丁氧苯基)-4-甲基噻唑-5-羧酸。结论:本法为非布司他的质量控制提供科学依据。
[Abstract]:Objective: to isolate and identify the side reactions and degradation of related substances of non-burestat. Methods: three impurities in the raw materials of non-burestat were identified by LC-MS. The chromatographic column was Diamonsil C18 (200mm 脳 4.6mm) and the mobile phase was methanol-0.1% acetic acid (60: 40). The flow rate was 1.0 mL 路min-1; Two of the impurities were isolated from non-Bustana by preparative high performance liquid chromatography (PHPLC). The structure was further confirmed by IR and NMR. Results: the by-reaction product was estimated to be 2-butadiene-3-methylidene (hydroxyimide) -4-isobutoxophenyl). 4-methylthiazole-5-carboxylic acid and 5-butanoboxybenzoic acid (2-methylthiazole-2-butoxobenzoic acid). The main degradation product was 2-butanoyl -4-isobutyloxyphenyl butadiene-4-methylthiazole-5-carboxylic acid. Conclusion: this method provides scientific basis for the quality control of non-burestar.
【作者单位】：合肥医工医药有限公司;
【分类号】：R927.2;O657.63
【正文快照】： 药品中杂质的存在可显著影响其有效性和安全性,ICH分别于2002年及2003年颁布了药品杂质研究指导原则(Q3A、Q3B),将有机杂质分为特定杂质和非特定杂质,并根据日使用剂量规定了相应限度,其中特定杂质包括结构已知的杂质[1-2]。特定杂质的限度制定,只有基于杂质定性研究,其制定才

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