国产注射用阿洛西林钠的质量评价

目的 评价国内不同企业生产的注射用阿洛西林钠的质量现状，并分析存在的问题。方法 采用法定标准检验结合探索性研究，并对检验结果进行统计分析。结果 按法定标准检验100批样品，合格率为99%，1批样品溶液的澄清度不合格，主要归因于产品的低酸度和高水分协同作用加速主药酸化成难溶的阿洛西林酸。探索性研究开展了有关物质方法优化并重新评价有关物质水平，合格率为100%；采用LC/MS建立了杂质谱，并对主要杂质的来源进行归属；阿洛西林二聚物为主要聚合物，优化后的有关物质系统可对其同步控制；稳定性试验与多因素相关分析表明高碱度与高水分对本品降解有一定促进作用，而低酸度易增加本品配伍析出的风险。结论 目前国产注射用阿洛西林钠的整体质量一般，各企业产品存在不同程度的质量差异。原料工艺控制水平直接影响产品质量，酸碱度及水分是影响本品质量的关键因素，相关企业应对原料进行优选并提高生产工艺控制水平。现行标准无法有效控制有关物质和聚合物，酸碱度及水分的限度水平有待提高，标准亟待修订。

Quality assessment of domestic azlocillin sodium for injection

Objective To evaluate the quality status of azlocillin sodium for injection of different domestic manufacturers. Methods The statutory testing methods combined with exploratory researches were used to evaluate the quality by statistical analysis of the results. Results According to the statutory standards for the examination of the 100 batches of samples, the qualified rate was 99%. The unqualified item was the clarity of solution due to the reduced solubility by acidity and moisture. A method for detecting the related substance was established, and the qualified rate of related substance was 100%. The major polymer impurities (dimers) can be controlled by the optimized method of related substances. Exploratory researches identified the structures and the source of major impurities by LC/MS. The stability study and multi-factors correlation analysis demonstrated that the high alkalinity and moisture promoted the degradation of the sample. Meanwhile, the low acidity increased the risk of compatible stability. Conclusion The overall quality of azlocillin sodium for injection is generally acceptable presently. The acidity and moisture were closely related to the quality of azlocillin sodium, and the quality of raw materials was the key to the quality of products. It is suggested that the domestic enterprises should optimize the raw materials and production processes to improve the product quality. The current standard needs to be further improved by optimizing the examination of related substance and polymers, and the limits of acidity and moisture should be adjusted simultaneously.