Establishment of the First National Reference Material for Low Molecular Weight Heparin / 中国药学杂志

ABSTRACT

OBJECTIVE: In June 2017, the National Pharmacopoeia Committee published on the internet the draft of national standards for dalteparin sodiumenoxaparin sodium and nadroparin calcium. As the new monographs to be added to the Chinese Pharmacopoeia in 2020. To establish the first batch national standards of low molecular weight calirantdalteparin sodiumenoxaparin sodium and nadroparin calcium for system suitability. METHODS: A national collaborative study involving thirteen laboratories had taken place, organized by National Institutes for Food and Drug Control(NIFDC)to provide supporting data for the establishment of the 1st national standards of low molecular weight heparin for molecular weight calibrantdalteparin sodium enoxaparin sodium and nadroparin calcium for system suitability of molecular weight determinations. The molecular weight determination methods in draft standards were used in the national collaborative study. The 2nd international standard low molecular weight heparin for molecular weight calibration(05/112) were used as molecular weight calibrant. The candidate national standards of low molecular weight heparin for molecular weight calibration (140820-201801) and the candidate dalteparin sodium(140811-201801) enoxaparin sodium(140810-201801) nadroparin calcium(140812-201801)for system suitability of molecular weight determination were tested in the study. RESULTS: The cumulative percent of peak area at the 18 molecular points from 600-18 000 of the candidate national standard of low molecular weight heparin for molecular weight calibration (140820-201801) were calculated. Based on the statistical analysis, the candidate gave low intra- and inter-laboratories variations.Of all 13 laboratories, standard deviations (SD) of two laboratories ranged from 1% to 2%,the others were less than 1%.Between laboratories, SD were all less than 1%,relative standard deviation(RSD) were all less than 5% except two points of the small molecular. The intra-lab SD of the test to determine the molecular weight of the candidate dalteparin sodium(140811-201801) enoxaparin sodium(140810-201801) nadroparin calcium(140812-201801)for system suitability of molecular weight determination was between 4 and 110,RSD was less than 2.5%. The inter-lab SD were less than 30, RSD was less than 1.0%. CONCLUSION: After the examination of the expert committee on pharmaceutical standardization, the candidate (140820-201801) was approved as the first national standard of low molecular weight heparin for molecular weight calibration, the broad standard table is also provided the broad standard table. The candidate(140811-201801) is approved as the first national standard of dalteparin sodium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 6 268. The candidate(140810-201801) is approved as the first national standard of enoxaparin sodium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 4 435. The candidate(140812-201801) was approved as the first national standard of nadroparin calcium for system suitability of molecular weight determination, with an assigned molecular weight (Mw) of 4 832.