目的 欧洲药品质量管理局(European Directorate on Quality of Medicines,EDQM)和英国国家生物制品检定所(National Institute for Biological Standards and Control,NIBSC)组织国际协作标定,建立第2批和第3批欧洲药典(European Pharmacopoeia,EP)低分子肝素(low molecular weight heparin,LMWH)相对分子质量对照品。方法 标定分为2个阶段,中国食品药品检定研究院(National Institutes for Food and Drug Control,NIFDC)参加了第二阶段的标定工作,采用EP中收载的高效体积排阻色谱法,用首批相对分子质量对照品(CRS1)和换批对照品(cCRS2、cCRS3)对7个市场上销售的具有不同相对分子质量及分布的低分子肝素产品(A~G)进行测定。结果 cCRS2和cCRS3数均相对分子质量(number average molecular mass,M_n)的最初赋值为3 700,测定结果表明,该赋值使cCRS2和cCRS3的计算结果与CRS1存在较大的系统误差,于是调整M_n赋值为3 800,经重新计算,cCRS2与cCRS3和CRS1的计算结果十分接近。NIBSC还对相对分子质量测定方法进行了规范。结论 待标品(cCRS2、cCRS3)可以作为EP的低分子肝素相对分子质量对照品使用,M_n=3 800。

An international collaborative study involving fourteen laboratories has taken place, organized by the European Directorate on Quality of Medicines(EDQM)and National Institute for Biological Standards and Control(NIBSC)to provide supporting data for the establishment of replacement batches of calibration chemical reference substance(CRS)for low molecular weight heparin(LMWH). METHODS The study was organized in two phases:A prequalification(phase 1, performed in three laboratories in 2005)followed by an international collaboration study(phase 2). Our institute(National Institutes for Food and Drug Control,NIFDC)took part in the phase 2 study started in March 2006. The molecular mass parameters were determined for seven different LMWH samples using the current CRS(CRS1)and two batches of candidate replacement material(cCRS2 and cCRS3)with a defined number average molecular mass(M_n)of 3 700 determined in phase 1. RESULTS The calculated values of cCRS2 and cCRS3 were systematically different from the values calculated using CRS1 with its assigned M_n of 3 700. Using the raw data supplied by other participants, the molecular mass parameters were recalculated using cCRS2 and cCRS3 with values for M_n of 3 800 and 3 900. The calculated values using these M_n values agreed more closely with those calculated using CRS1, supporting the fact that the candidates, though similar in view of the production processes, differed slightly from CRS1 in terms of molecular mass distribution. CONCLUSION The establishment of cCRS2 and cCRS3 could be recommended with an assigned M_n value of 3 800 that is consistent with both the phase 1 results and the determination result of current CRS1.