首批肝素抗Ⅱa因子效价测定用国家标准品协作标定

A collaborative study to establish the national standard for heparin with an assigned value obtained from anti-FIIa chromogenic method

目的建立肝素抗Ⅱa因子效价测定用国家标准品。方法通过理化分析及效价测定,筛选出适合的标准品原料,溶解、分装、冻干后制备成肝素国家标准物质待标品(140817-201501)。以第6次肝素国际标准品07/328为标准品,分别采用《中国药典》2015年版和2010年版肝素钠效价测定方法测定待标品的抗Ⅱa因子效价、抗Ⅹa因子效价和抗凝效价,由13个实验室协作标定。为考察肝素国家标准品的延续性,上一批肝素钠国家标准品(150509-200912)在协作标定中使用。结果效价标化结果经统计学分析,实验室内及实验室间的几何变异系数(geometric coefficient of variation,gcv)均小于10%;以第6次肝素国际标准品07/328作为标准品,待标品抗Ⅱa因子效价为2011 IU/安瓿,抗Ⅹa因子效价为1998 IU/安瓿,抗凝效价为1992 IU/安瓿;对各实验室抗Ⅱa因子效价、抗Ⅹa因子效价、抗凝效价几何均值进行单因素方差分析,结果没有显著性差异;各实验室使用国际标准品测定待标品抗Ⅱa因子效价和使用上一批肝素钠国家标准品(150509-200912)测定的待标品抗凝效价几何均值进行welch检验,结果没有显著性差异,肝素国家标准品的延续性良好。结论经国家药品标准物质委员会审定后批准,待标品(140817-201501)用作肝素效价测定用国家标准品,效价为2011 IU/安瓿。

Objective To establish a national standard for heparin with an assigned value obtained from anti-FIIa chromogenic method.Methods Through physical,chemical and biological tests,one batch of heparin sodium was selected to prepare the national standard for heparin assay.The bulk material was dissolved with distilled water,distributed into ampoules and freeze-dried. The candidate sample（ 140817-201501） was assayed against the 6thinternational standard（ 07 /328）. Thirteen laboratories took part in the study. Three methods were used in the study,including anti-FIIa chromogenic assay,anti-FXa chromogenic assay and clot-based plasma assay. For the purpose of the continuity check between subsequent batch of national standard,the current heparin national standard for assay（ 150509-200912） was also included in the study. Results Based on the statistical analysis,the candidate gave low intra- and inter-laboratories variations,geometric coefficient variations were all less than 10%. Against the 6th international standard（ 07 /328）,Anti-FIIa potency of the candidate sample（ 140817-201501） was 2011 IU per ampoule,anti-FXa potency was 1998 IU per ampoule,anticoagulation potency was 1992 IU per ampoule. The results between three methods were not significant difference by statistics analysis.The results between international standard（ 07 /328） and national standard（ 150509-200912） were not significant difference by statistics analysis. The continuity of the national standard of heparin is good. Conclusion After the examination of the expert committee on pharmaceutical standardization,the candidate（ 140817-201501） was approved as the national standard of heparin for assay with an assigned value 2011 IU per ampoule.