【摘要】：目的：針對(duì)當(dāng)前酚磺乙胺注射液質(zhì)量分析研究及整體質(zhì)量評(píng)價(jià)的不足,通過(guò)按法定標(biāo)準(zhǔn)檢測(cè)和按自擬的探索性研究方法測(cè)試,評(píng)價(jià)該品種法定標(biāo)準(zhǔn)的控制水平、企業(yè)對(duì)生產(chǎn)過(guò)程的控制水平及該品種的整體質(zhì)量狀況,為提高該品種的安全性探索可行的方法。 方法：首先按法定質(zhì)量標(biāo)準(zhǔn)逐項(xiàng)對(duì)樣品進(jìn)行檢測(cè),并對(duì)數(shù)據(jù)進(jìn)行統(tǒng)計(jì)分析；其次緊緊圍繞藥品的安全性和質(zhì)量標(biāo)準(zhǔn)的可控性,進(jìn)一步開(kāi)展探索性研究,包括：HPLC-MS法雜質(zhì)分析、雜質(zhì)單體的制備及結(jié)構(gòu)確證、GC法殘留溶劑考察、比色法亞硫酸鹽類抗氧劑研究、HPLC法EDTA的含量測(cè)定及滅菌工藝研究等,最后對(duì)該品種的整體質(zhì)量進(jìn)行了全面的評(píng)價(jià)。 結(jié)果：依據(jù)現(xiàn)行法定標(biāo)準(zhǔn)進(jìn)行全檢,合格率為100%,但現(xiàn)行標(biāo)準(zhǔn)項(xiàng)目設(shè)置簡(jiǎn)單,可控性較差,缺少重要安全性指標(biāo),不能全面反映本品的質(zhì)量。雜質(zhì)研究發(fā)現(xiàn),本品目前檢測(cè)到的雜質(zhì)均由原料引入,其中已知雜質(zhì)氫醌已得到較好控制,最大單個(gè)雜質(zhì)經(jīng)結(jié)構(gòu)確證,初步推測(cè)其為原料藥合成的副產(chǎn)物,其產(chǎn)生與企業(yè)的工藝控制水平有關(guān)。原料藥的殘留溶劑得到較好控制,未檢出1,2一二氯乙烷,少量檢出乙醇,符合藥典相關(guān)要求。輔料研究結(jié)果顯示,個(gè)別企業(yè)的處方中抗氧劑的使用量超出了中國(guó)藥典的要求、EDTA-2Na的使用量高出其他企業(yè)10倍有余；個(gè)別企業(yè)可能存在未按處方非法添加EDTA-2Na的情況；輔料抗氧劑及EDTA-2Na能極大的增加制劑的細(xì)胞毒性。滅菌工藝研究結(jié)果顯示目前本品的滅菌方式不能滿足F0值大于8的要求,存在一定的安全隱患,無(wú)菌保證度存在可提升的空間。 結(jié)論：該品種現(xiàn)行法定標(biāo)準(zhǔn)存在著一些重要項(xiàng)目的缺失,急需進(jìn)一步完善。該品種批準(zhǔn)文號(hào)、生產(chǎn)企業(yè)眾多,各企業(yè)處方工藝存在差異,生產(chǎn)工藝控制水平不一致,導(dǎo)致產(chǎn)品內(nèi)在質(zhì)量存在較大差異,需要進(jìn)一步優(yōu)化。圖50幅,表21個(gè),參考文獻(xiàn)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.
【學(xué)位授予單位】：中南大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R927.1

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