肝素中残留蛋白质检测国际协作研究

USP heparin protein impurities round robin study

目的:评价美国药典肝素中残留蛋白质检测新方法的适用性,收集多批原料药检测数据以便确定适合的限度。方法:采用Lowry法及加入去除干扰物质的前处理过程的Lowry法对美国药典委员会提供的2个测试样品及2个国内生产厂家的10批肝素钠原料药进行了检测。结果:中检院2个测试样品结果符合USP要求,提交的实验数据全部被采纳。全球共14个实验室提交了141批肝素钠原料药结果,除1个实验室不符合系统适用性要求,数据未被采纳外,其余原料蛋白含量均小于0.1%。结论:美国药典新的肝素中残留蛋白质检测方法及限度是可行的,对预实验蛋白质含量超过0.1%的样品,进行去干扰物质预处理,将残留蛋白质限度从"不得过1.0%"提高至"不得过0.1%"。

Objective： To evaluate the applicability of the new protein impurities detection method of heparin in the United States Pharmacopeia（USP）.Collect data of active pharmaceutical ingredients（APIs） in order to determine the appropriate limits. Methods： Two USP proficiency samples and 10 bathes API from two manufactories were tested by Lowry method with interfering substances treatment（IST） and without IST. Results： Fourteen laboratories from all over the world participated the study,141 API samples were tested.Data from our institute have been all adopted.One laboratory did not meet the protocol specified system suitability requirements.Except those data,no values were outside the acceptable limits. Conclusion： The new protein impurities detection method of heparin in USP is feasible.Treatment for interfering substances is only required for samples previously tested with a protein content greater than 0.1%.The statistical analyses support the proposed USP heparin sodium monograph acceptance limits for protein impurities from ＂no more than 1.0%＂ to ＂no more than 0.1%＂.