首批依诺肝素钠国家对照品1,6-脱水衍生物含量赋值的协作研究

目的： 建立首批1,6-脱水衍生物系统适用性对照品,完善国家标准。方法：以欧洲药典依诺肝素钠对照品(EP Enoxaparin Sodium,Batch5)为系统适用性对照品,采用依诺肝素钠新国家标准草案 “1,6-脱水衍生物”检查法,对依诺肝素钠国家对照品(批号：140810-201801)进行1,6-脱水衍生物含量测定,由全国14个药品检验机构及依诺肝素生产企业实验室协作标定。结果：对依诺肝素钠系统适用性国家对照品(批号：140810-201801)1,6-脱水衍生物含量标定结果为20.3%,并对实验室内误差进行考察,14个实验室中有1个实验室(Lab1)标准差(SD)为1.8%,5个实验室(Lab2、Lab4、Lab10、 Lab11和Lab13)的SD为0.5%~0.7%,其余8个实验室的SD值均小于0.5%。对实验室间误差进行考察,有效数据的SD值为0.6%,相对标准偏差(RSD)为3.2%。结论：经国家药品标准物质委员会审定后批准, 依诺肝素系统适用性国家对照品(批号：140810-201801)增加1,6-脱水衍生物含量赋值,可以用于依诺肝素钠1,6-脱水衍生物检查系统适用性考察使用。

The Collaborative Study on the Content Assignment of 1,6-anhydro Derivatives of the 1st Enoxaparin National Standard

Objective: The new draft of National standard for enoxaparin sodium has added the determination item of 1,6-anhydro derivatives. The 1st batch of 1,6-anhydro derivatives of national reference standard should be established for systematic applicability. Methods: The European Pharmacopoeia enoxaparin sodium reference substance (EP enoxaparin sodium, batch 5) was used as the system applicability reference substance. The national standard (batch number: 140810-201801) of enoxaparin was used to determine the content of 1,6-anhydro derivatives by the new national standard draft "1, 6-dehydrated derivatives" examination method, which was determined by 14 national drug inspection institutions and laboratories of enoxaparin manufacturers. Results: The content calibration result of 1,6-anhydroderivatives was 20.3% in the national standard (batch number: 140810-201801) applicable to enoxaparin sodium system, and the laboratory errors were investigated. Among the 14 laboratories, the standard deviation (SD) of 1 laboratory (Lab1) was 1.8%, the SD of 5 laboratories (Lab2, Lab4, Lab10, Lab11 and Lab13) was 0.5%-0.7%, and the SD values of the remaining 8 laboratories were all less than 0.50%. When the interlaboratory errors were examined, the SD of the valid data was 0.6%, and the relative standard deviation (RSD) was 3.2%. Conclusion: After approval by National Drug Standard Substances Committee, the national standard applicable to enoxaparin sodium (batch number: 140810-201801) was approved to add the content assignment value of 1,6-anhydro derivatives. This national standard could be used in the test of enoxaparin 1,6-dehydrated derivatives in enoxaparin sodium Chinese national standard.