目的: 研制首批N, S-二乙酰半胱氨酸国家药品对照品,用于氨基酸类药品有关物质的检查,控制相关药品质量,保证患者用药安全。方法: 采用高效液相色谱、红外吸收光谱、高分辨质谱及核磁共振谱对N, S-二乙酰半胱氨酸化学结构进行确证,检查其水分、炽灼残渣、无机离子、残留溶剂、有关物质等杂质的含量,采用液相色谱法、核磁共振谱定量法及质量平衡法对其含量进行测定和计算,并采用质量平衡法对其含量进行赋值,考察了其引湿性、均匀性和短期稳定性。 结果与结论: 试验确证了N, S-二乙酰半胱氨酸的分子结构,测得水分为0.05%,无机离子为0.21%,有关物质为0.90%,未检出残留溶剂。以质量平衡法赋值首批N, S-二乙酰半胱氨酸对照品,含量为98.8%。本批次对照品含量分布均匀,试验结果证明N, S-二乙酰半胱氨酸短期内稳定。

Objective: To establish the first batch of national drug reference standard of N, S-diacetylcysteine which is used for the inspection for related substances of amino acid drugs to control the drug quality and guarantee the drug safety. Methods: The molecular structure of N, S-diacetylcysteine was confirmed by the methods of HPLC, IR, NMR and high resolution MS. Moreover, the moisture, residual solvents, residual ignition, inorganic ions and related substances of N, S-diacetylcysteine were all determined. HPLC, Mass Balance and NMR were applied to determine and calculate its content, and Mass Balance mehod was used for evaluating its final content. Finally, its hygroscopicity, homogeneity and short-term stability were also observed. Results and Conclusion: The results of experiments showed the structure of N, S-diacetylcysteine was confirmed, and its contents of moisture, inorganic ions and related substances were 0.05%, 0.21% and 0.90%, respectively. The residual solvents were not detected in the samples. The final content of N, S-diacetylcysteine reference standard was 98.8% by mass balance method. The content distribution of this batch of N, S-diacetylcysteine reference standard was uniform, and its short-term stability result proved that N, S-diacetylcysteine was stable.