人血白蛋白中铝离子含量稳定性试验结果的探讨

Investigation on the stability test results of aluminum content in human albumin

目的:考察人血白蛋白铝离子含量的稳定性。方法:根据抽样原则,选取生产时间在2013年至2017年之间的158批人血白蛋白样品(4家国内生产企业共90批次,6家进口企业共68批次),按《中国药典》2015年版四部通则3208人血白蛋白铝残留量测定法,分别测定样品在批签发发行时(储存时间<8个月)与有效期内(储存时间为9个月至有效期内)的铝离子含量;并对其中29批次样品(4家国内生产企业共17批次,6家进口企业共12批次)进行加速稳定性试验(温度为30℃,湿度为65%)。结果:29批次的国产人血白蛋白有效期内的铝离子含量超过200μg·L^-1。国产人血白蛋白铝离子含量与储存时间呈高度相关,进口人血白蛋白铝离子含量与储存时间呈低度相关;人血白蛋白铝离子含量与加速稳定性试验(温度为30℃,湿度为65%)放置时间无相关性。长期稳定性试验中,采用特殊设计的多层聚乙烯塑料瓶作为包装材料的人血白蛋白铝离子含量增加率最低,其次为中性化处理的钠钙玻璃瓶,最高的为中性硼硅玻璃瓶。结论:长期稳定性试验结果表明本品在有效期内铝离子含量均呈上升趋势;加速稳定性试验(温度为30℃,湿度为65%)结果表明,本品铝离子含量无明显变化。药品包装材料对人血白蛋白铝离子含量增加有一定影响。

Objective : The stability of aluminum content in human albumin was investigated. Methods :According to the sampling principle, 158 batches of human albumin samples (90 batches from 4 domestic manufacturers and 68 batches from 6 imported manufacturers) produced in 2013 to 2017 were selected. The aluminum contents of these samples were determined at the batch release (storage time less than 8M) and in shelf life (storage time 9M until expiry date) respectively according to the atomic absorption spectrophotometry method for the determination of aluminum content in general rule 3208 of Chinese Pharmacopoeia 2015Vol Ⅳ. The accelerated stability tests were carried out with 29 batches of samples (17 batches from 4 domestic manufacturers and 12 batches from 6 imported manufacturers) under the condition of 30 ℃/65% relative humidity(RH). Results :The aluminum contents of 29 batches of domestic human albumin were over 200 μg·L^-1 within shelf life. The aluminum contents of domestic human albumin were highly correlated with storage time, but aluminum contents of imported human albumin was lowly correlated with storage time. There was no correlation between the content of aluminum in human albumin and the storage time of accelerated stability test at 30℃/65%RH. The long-term stability test results showed that the increase of aluminum contents in human albumin with different packaging materials was as follow: the least increase for special design of multilayer polyethylene plastic bag, middle increase for neutralized sodium calcium glass bottle, and the highest increase for neutral borosilicate glass bottle. Conclusion :The results of long-term stability test show that the aluminum contents of human albumin have the increase trends within shelf life. The results of accelerated stability tests at 30℃/65% RH showed that the aluminum contents of human albumin have no obvious change. The pharmaceutical packaging materials have a certain effect on the increase of aluminum content in human albumin.