布洛芬软胶囊的有关物质研究

发布时间：2018-09-01 12:38

【摘要】：目的:对布洛芬软胶囊中的杂质情况进行分析,考察了最大未知杂质的结构和来源。方法:采用高效液相色谱法测定布洛芬软胶囊中的已知和未知杂质;通过原料和制剂强制降解试验考察了样品中已知杂质和最大未知杂质的来源;采用LCMS联用鉴定最大的未知杂质的结构,并合成该未知杂质;MS和NMR确证了未知杂质的结构,推测其主要的裂解途径;模拟体内胃、肠的酸碱环境,考察未知杂质在体内的水解情况。结果:对比已知混合杂质对照品色谱图的保留时间,实际样品中存在已知杂质D、J、N和E;原料强制降解后可产生已知杂质D、J、N和E,最大的未知杂质仅由制剂强制降解后产生;通过结构的确证表明,未知杂质为布洛芬与辅料甘油发生反应脱一分子水缩合产生的布洛芬甘油酯,结构为2-(4-异丁基)苯基-6,7-二羟基-丙酸丙酯,在体内环境中不能水解形成布洛芬。结论:生产布洛芬软胶囊时应避免采用甘油作为辅料,布洛芬软胶囊有关物质检查法中应明确对布洛芬甘油酯杂质的限度控制。
[Abstract]:Objective: to analyze the impurity in ibuprofen soft capsules and investigate the structure and source of the largest unknown impurity. Methods: the known and unknown impurities in ibuprofen soft capsules were determined by HPLC. The structure of the largest unknown impurity was identified by LCMS, and the unknown impurity was synthesized by MS and NMR. The structure of the unknown impurity was confirmed and its main cleavage pathway was inferred. The hydrolysis of unknown impurities in vivo was investigated. Results: compared with the retention time of the chromatogram of the known mixed impurity reference substance, there were known impurity DJJ N and E in the actual sample, and the known impurity DX JJ N and E could be produced after the forced degradation of the raw material, and the largest unknown impurity was produced only after the preparation forced degradation. The structure confirmed that the unknown impurity is ibuprofen glycerol ester which is produced by the reaction of ibuprofen and excipient glycerol, and the structure is 2- (4-isobutyl) phenyl-6-dihydroxy propyl propionate. Ibuprofen cannot be hydrolyzed in vivo to form ibuprofen. Conclusion: glycerol should be avoided in the production of ibuprofen soft capsules, and the limit of the impurity of ibuprofen glycerol ester should be clearly controlled in the examination method of ibuprofen soft capsules.
【作者单位】：湖北食品药品监督检验研究院;
【分类号】：R927

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