氢氧化铝佐剂内控质量标准的建立

Development of internal quality control standard for aluminum hydroxide adjuvant

目的建立氢氧化铝佐剂的内控质量标准。方法参照《欧洲药典》7.0对氢氧化铝佐剂进行吸附能力、沉降率、细菌内毒素、无机盐及金属离子的检测,并对30批氢氧化铝佐剂的p H值、氢氧化铝含量、残留氨含量进行趋势分析,建立氢氧化铝佐剂的内控质量标准。结果建立了氢氧化铝佐剂的内控质量标准13项（1.5 mg铝完全吸附1、2、3 mg/ml BSA溶液中的蛋白,5、8和10 mg/ml BSA的溶液中有残留蛋白,且残留的蛋白呈一定的浓度梯度;铝含量为1 mg/ml时,上清液小于20 ml;内毒素含量每毫克铝〈5 IU;氯化物≤0.33%;硝酸盐≤100 ppm;硫酸盐≤0.5%;铵盐≤50 ppm;砷盐≤1 ppm;铁盐≤15 ppm;重金属≤20 ppm;p H值4.19-5.25;氢氧化铝含量6.87-12.78 mg/ml;残留氨含量〈0.04%）,涵盖了《欧洲药典》要求的所有项目。结论建立了氢氧化铝佐剂的质量评价体系,填补了国内氢氧化铝佐剂质量评价方面的空白,为全面、客观评价氢氧化铝佐剂的质量提供了依据。

Objective To develop an internal quality control standard for aluminum hydroxide adjuvant. Methods The parameters,such as adsorption capacity,sedimentation rate,bacterial endotoxin,inorganic salts and heavy metal ions of aluminum hydroxide adjuvant were determined according to the requirements in Europe Pharmacopoeia 7. 0. Trend analysis of p H,aluminum hydroxide content and residual ammonia content in 30 batches of aluminum hydroxide adjuvant was carried out,based on which the internal quality control standard for aluminum hydroxide adjuvant was developed.Results The internal control quality standard for 13 items was developed,which covered all the items provided in the European Pharmacopoeia as follows： the proteins in 1,2 and 3 mg / ml BSA solutions are completely adsorbed with 1. 5 mg aluminum adjuvant,while the residual proteins are detected in a concentration density in 5,8 and 10 mg / ml BSA;the volume of supernatant is less than 20 ml when the aluminum content is 1 mg / ml;the endotoxin content in each microgram of aluminum is less than 5 IU; the chloride content is not more than 0. 33%;the nitrate content was not more than 100 ppm; the sulfate content was not more than 0. 5%;the ammonium salt content was not more than 50 ppm;the arsenic salt content was not more than 1 ppm; the iron salt content was not more than 15 ppm; the heavy metal content was not more than 20 ppm; the p H value was 4. 19 - 5. 25;the aluminum hydroxide content was 6. 87 - 12. 78 mg / ml;the residual ammonia was less than 0. 04%. Conclusion The quality evaluation system of aluminum hydroxide adjuvant was established,which filled up a gap of quality evaluation on aluminum hydroxide adjuvant in China,and provided a basis for evaluating the quality of aluminum hydroxide adjuvant comprehensively and objectively.