首批肝素相对分子质量国家对照品的建立

目的《中国药典》2015年版二部肝素钠、肝素钙新增相对分子质量与相对分子质量检查项,需建立首批肝素相对分子质量国家对照品及系统适用性对照品。方法以《美国药典》肝素相对分子质量测定用对照品(USP heparin sodium molecular weight calibrant,批号:F0L483)为肝素相对分子质量对照品,以《美国药典》肝素相对分子质量系统适用性对照品(USP heparin sodium identification,批号:G1L413)为肝素相对分子质量系统适用性对照品,采用《中国药典》2015年版二部肝素钠“相对分子质量与相对分子质量分布”检查法,对肝素相对分子质量国家对照品待标品(批号:140819-201501)及肝素国家对照品待标品(批号:140818-201501)进行相对分子质量与相对分子质量分布测定,由全国12个药检所及肝素生产厂家实验室协作标定。结果对肝素相对分子质量国家对照品待标品(批号:140819-201501)相对分子质量5000~42000的20个点的百分面积进行标定,对实验室内误差进行考察,12个实验室中有2个实验室(2号、7号)部分点的标准差(standard deviation,SD)为1%~2%,其余10个实验室的SD值均小于1%,对实验室间误差进行考察,20个数据点的SD值均小于1%。相对标准偏差(relative standard deviation,RSD)均小于10%。肝素国家对照品待标品重均相对分子质量实验室内SD值除2号实验室外,其余实验室SD小于180,实验室间SD为180,实验室间RSD为1.1%。结论经国家药品标准物质委员会审定后批准,肝素相对分子质量国家对照品待标品(批号:140819-201501),附带宽分布标样表,及肝素国家对照品待标品(批号:140818-201501),重均相对分子质量16200,可以用于《中国药典》2015年版二部肝素钠、肝素钙相对分子质量与相对分子质量分布检查使用。

National Collaborative Study to Establish the 1^st National Standards of Heparin Molecular Weight Calibrant and Heparin for System Suitability of Molecular Weight Determinations

OBJECTIVE Molecular weight determinations of heparin sodium and heparin calcium were added in Chinese Pharmacopoeia(2015).To establish the 1st national standards of heparin molecular weight calibrant and heparin for system suitability of molecular weight determinations were needed to establish.METHODS An national collaborative study involving twelve laboratories had taken place,organized by National Institutes for Food and Drug Control(NIFDC)to provide supporting data for the establishment of the 1st batches of heparin molecular weight calibrant and heparin for system suitability of molecular weight determinations standard.The method of heparin molecular weight determinations in Chinese Pharmacopoeia(2015)was used in the national collaborative study.The USP heparin sodium molecular weight calibrant RS(F0L483)was used as molecular weight calibrant.The USP heparin sodium identification RS(G1L413)was used as the standard of system suitability.The candidate national standards of heparin molecular weight calibrant(140819-201501)and the candidate heparin for system suitability of molecular weight determination standard(140818-201501)were tested in the study.RESULTS To be calculated the cumulative percent of peak area at the 20 molecular points from 5000-42000 of the candidate national standard of heparin molecular weight calibrant(140819-201501).Based on the statistical analysis,the candidate gave low intra-and inter-laboratories variations.In laboratories,standard deviations(SD)of two laboratories ranged from 1%to 2%,others were less than 1%.Between laboratories,SD were all less than 1%,relative standard deviation(RSD)was all less than 10%.The intra-lab SD of the test to determine the molecular weight of the candidate heparin for system suitability of molecular weight determinations standard(140818-201501)was less than 180,except Lab 2.The inter-lab SD was 180.The RSD was 1.1%.CONCLUSION After the examination of the expert committee on pharmaceutical standardization,the candidate(140819-201501)is approved as the first national standard of heparin molecular weight calibrant,provides the broad standard table.The candidate(140818-201501)is approved as the first national standard of heparin for system suitability of molecular weight determinations,with an assigned molecular weight(Mw)of 16200.The two national standards can be used in the test of heparin molecular weight determinations in Chinese Pharmacopeia(2015).