酚磺乙胺注射液质量分析研究及整体质量评价

发布时间：2018-08-26 19:43

【摘要】：目的：针对当前酚磺乙胺注射液质量分析研究及整体质量评价的不足,通过按法定标准检测和按自拟的探索性研究方法测试,评价该品种法定标准的控制水平、企业对生产过程的控制水平及该品种的整体质量状况,为提高该品种的安全性探索可行的方法。方法：首先按法定质量标准逐项对样品进行检测,并对数据进行统计分析；其次紧紧围绕药品的安全性和质量标准的可控性,进一步开展探索性研究,包括：HPLC-MS法杂质分析、杂质单体的制备及结构确证、GC法残留溶剂考察、比色法亚硫酸盐类抗氧剂研究、HPLC法EDTA的含量测定及灭菌工艺研究等,最后对该品种的整体质量进行了全面的评价。结果：依据现行法定标准进行全检,合格率为100%,但现行标准项目设置简单,可控性较差,缺少重要安全性指标,不能全面反映本品的质量。杂质研究发现,本品目前检测到的杂质均由原料引入,其中已知杂质氢醌已得到较好控制,最大单个杂质经结构确证,初步推测其为原料药合成的副产物,其产生与企业的工艺控制水平有关。原料药的残留溶剂得到较好控制,未检出1,2一二氯乙烷,少量检出乙醇,符合药典相关要求。辅料研究结果显示,个别企业的处方中抗氧剂的使用量超出了中国药典的要求、EDTA-2Na的使用量高出其他企业10倍有余；个别企业可能存在未按处方非法添加EDTA-2Na的情况；辅料抗氧剂及EDTA-2Na能极大的增加制剂的细胞毒性。灭菌工艺研究结果显示目前本品的灭菌方式不能满足F0值大于8的要求,存在一定的安全隐患,无菌保证度存在可提升的空间。结论：该品种现行法定标准存在着一些重要项目的缺失,急需进一步完善。该品种批准文号、生产企业众多,各企业处方工艺存在差异,生产工艺控制水平不一致,导致产品内在质量存在较大差异,需要进一步优化。图50幅,表21个,参考文献66篇。
[Abstract]:Objective: to evaluate the quality control level of phenolsulfonethylamine injection by testing according to the legal standard and according to the self-made exploratory research method, aiming at the deficiency of the quality analysis and overall quality evaluation of phenolsulfonamide injection. The control level of the production process and the overall quality of the variety are discussed in order to improve the safety of the variety. Methods: first of all, the samples were detected item by item according to the legal quality standard, and the data were analyzed statistically. Secondly, further exploratory research was carried out around the safety of drugs and the controllability of the quality standards, including the analysis of impurities by the method of: HPLC-MS. Preparation and structure confirmation of impurity monomers. Investigation of residual solvents by GC, determination of EDTA content by colorimetric sulfite antioxidant, and study of sterilizing technology. Finally, the overall quality of the variety was evaluated. Results: according to the current legal standard, the qualified rate was 100, but the current standard item was simple, poor controllability and lack of important safety index, which could not reflect the quality of the product. The impurity study found that the impurities detected in this product were all introduced from raw materials, among which hydroquinone, a known impurity, had been well controlled. The largest single impurity was confirmed by its structure, and it was preliminarily assumed to be a by-product of raw material drug synthesis. Its production is related to the level of process control of the enterprise. The residual solvent of the crude drug was well controlled, no 1 ~ (2 +) -dichloroethane was detected, and a small amount of ethanol was detected, which met the requirements of pharmacopoeia. The results of excipient research show that the amount of antioxidant in prescriptions of individual enterprises exceeds the requirement of Chinese Pharmacopoeia and the usage of EDTA-2Na is more than 10 times higher than that of other enterprises. Excipient antioxidant and EDTA-2Na can greatly increase the cytotoxicity of the preparation. The results of sterilization technology showed that the sterilization method could not meet the requirement of F0 > 8, and there was some hidden trouble in safety, and there was room for aseptic assurance to be raised. Conclusion: there are some important items missing in the current legal standard of this variety, which need to be further improved. Because of the large number of production enterprises, the difference of prescription technology and the inconsistency of production process control level, the internal quality of the product has great difference, which needs further optimization. There are 50 pictures, 21 tables and 66 references.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R927.1

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