目的: 为有效控制比伐芦定注射剂的产品质量,研制比伐芦定首批含量测定用国家对照品,同时探索合成肽类标准物质定量赋值的其他方法。方法: 采用红外光谱、紫外光谱、液相色谱、质谱等技术对其进行结构确证,利用高效液相色谱法进行有关物质的测定,采用质量平衡法确定比伐芦定的含量,同时通过经肽纯度校正的肽含量方法进行验证,并对供试品进行均匀性和稳定性考察。结果: 首批比伐芦定国家对照品以C98H138N24O33计,含量为88.8%,均匀性和稳定性考察结果符合规定。结论: 根据合成肽的结构特点,采用不同方法进行定性与定量研究,可以确保国家对照品赋值的准确性。
Objective: To develop the first national reference standards for the quantitative determination of bivalirudin, in order to effectively control the product quality of bivalirudin injections, and to explore alternative methods for the quantitative characterization of synthetic peptide reference materials. Methods: Infrared (IR) spectroscopy, UV spectroscopy, HPLC, MS were used to confirm the structure of bivalirudin. Related substance were analyzed by HPLC. The mass balance method was used to determine the content of bivalirudin, which was further verified by a peptide content assay corrected for related peptide impurities. In addition, the stability and uniformity of the candidate reference material were evaluated. Results: The content of the first batch of bivalirudin national reference standard was 88.8%, calculated on C98H138N24O33, and the stability and uniformity tests met the required specifications. Conclusion: Based on the structural characteristics of the synthetic peptides, multiple qualitative and quantitative methods were used to ensure the accuracy of the content assignment for the national reference standard of bivalirudin.
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