注射用药用辅料枸橼酸细菌内毒素检查法的可行性研究

Study on the Determination Method of the Bacterial Endotoxins in the Injectable Auxiliary Material -Anhydrous Citric Acid

目的:建立注射用药用辅料枸橼酸的细菌内毒素检验方法。方法:按照《中国药典》2010年版二部附录细菌内毒素检查法试验和结果判断,采用供试品稀释法和pH调节法进行试验。结果:在供试品稀释法中,枸橼酸0.125 mg.mL-1及其以下浓度对湛江安度斯生物有限公司生产的鲎试剂与细菌内毒素反应无干扰;枸橼酸0.0625 mg.mL-1及其以下浓度对湛江博康海洋生物有限公司生产的鲎试剂与细菌内毒素反应无干扰。使用0.03 EU.mL-1的鲎试剂可对其进行细菌内毒素检查。在pH调节法中,枸橼酸用1 mol.L-1氢氧化钠调节pH值至6.0后,对鲎试剂与内毒素反应最大不产生干扰的浓度为0.5 mg.mL-1,使用0.25 EU.mL-1或灵敏度更高的鲎试剂可对其进行细菌内毒素检查。结论:建立其细菌内毒素检查法是可行的,可用于其质量控制。

Objective： To establish the bacterial endotoxins determination method for the injectable auxiliary material-anhydrous citric acid. Method： The experiment was carried on and the result was judged according to Chinese Pharmacopeia 2010 edition Vol. Ⅱ. The dilution method and pH modulation method were adopted. Results： With dilution method, maximum non-disturb concentration of anhy- drous citric acid for bacterial endotoxins test was 0. 125mg · mL-1 for Zhanjiang A＆C Biological Ltd. , The maximum non-disturb con- centration of anhydrous citric acid for bacterial endotoxins test was 0. 0625 mg · mL-1 for Zhanjiang Bokang Marine Biological Co Ltd. , With pH modulation method, after adding 1 mol· L-1 sodium hydroxide to adjust pH of the sample to 6.0, maximum non-disturb concentration of anhydrous citric acid for bacterial endotoxins test was 0. 5 mg · mL-1 when sensitivity of TAL was or more than 0. 25 EU · mL-1. Conclusion： The established method of endotoxins test is feasible; it can be used for the quality control of the Injectable auxiliary material-anhydrous citric acid.