注射用曲克芦丁发生临床ADR后动态浊度法测定细菌内毒素含量

Determination of bacterial endotoxin in troxerutin for injection by kinetic turbidimetric method after clinical ADR occurred

目的:建立细菌内毒素动态浊度法,定量检测涉药物不良反应ADR批次与正常批次注射用曲克芦丁中内毒素含量的差异。方法:依据《中华人民共和国药典》2015年版四部通则1143“细菌内毒素检查法”中动态浊度法,建立细菌内毒素检查的标准曲线并作可靠性分析,对供试品中的细菌内毒素进行定量检测。结果:经干扰预试验选择注射用曲克芦丁稀释40倍即1.25 mg·mL^(-1)浓度时对试验无干扰作用,细菌内毒素回收率均符合50%~200%范围要求,6批次供试品中内毒素含量均符合规定,但涉ADR的2个批次的内毒素含量显著高于合格样品。结论:建立的动态浊度法可用于定量检测注射用曲克芦丁的细菌内毒素含量,可更清晰、可靠地用于比较产品批次间质量差异。

Objective:To establish the kinetic turbidimetric method in order to detect the quantitative differences of bacterial endotoxin between ADR(Adverse Drug Reaction)batches and qualified batches of troxerutin for injection.Methods:According to the kinetic turbidimetric method in general chapters 1143 bacterial endotoxin test in the Chinese Pharmacopoeia 2015 VolⅣ,the standard curve of bacterial endotoxin test was established and the reliability analysis was made.Then bacterial endotoxin in test samples was tested with the established method.Results:The pre-interference test results showed that troxerutin for injection had no interference for bacteria endotoxin test at 40 times dilution(1.25 mg·mL^(-1)).The recoveries of bacterial endotoxin fell into the range of 50%-200%.The contents of endotoxin in 6 batches of samples met the criteria,but the contents of bacterial endotoxin in 2 ADR batches were significantly higher than that of qualified samples.Conclusion:The established kinetic turbidimetric method can be used to quantitatively detect the content of bacterial endotoxin in troxerutin for injection,and can be used to compare the quality between the different batches more clearly and reliably.