顺铂注射剂有关物质检查方法研究及杂质谱分析

目的：通过对顺铂注射剂的杂质进行分析，考察现行质量标准的科学性，探讨存在的问题，为提高标准及产品质量提供参考。方法：采用Merck Superspher RP-select B C₈色谱柱（4 mm×250 mm，4 μm），以含辛烷磺酸钠1.08 g·L^-1、四丁基硫酸氰铵1.70 g·L^-1、磷酸二氢钾2.72 g·L^-1的水溶液为流动相，流速1.0 mL·min^-1，检测波长210 nm，柱温30 ℃。结果：顺铂注射剂中检出的杂质主要为三氯氨铂和反铂，其中三氯氨铂为光照及高温降解产物，反铂为合成工艺杂质及光照和氧化降解杂质。按现行标准检验，检出含量约为0.3%的未知成分，经确认为顺铂一水合物，是有效活性成分，不应作为杂质控制。顺铂注射液剂型有关物质含量显著高于粉针剂型。结论：现行标准存在缺陷，有必要提高；对比不同剂型，注射用顺铂整体质量好于顺铂注射液；检出主要杂质为降解杂质，可通过采用棕色玻璃瓶及低温保存等一系列措施进一步提高药品质量。

Objective:To analyze the impurities in cisplatin injection,investigate and discuss the scientificalness of the current statutory standards and the status of the existing problems,and to provide a reference for improvement of the standards and the product quality.Methods:A Merck Superspher RP-select B C₈ column (4 mm×250 mm,4 μm) was used.An aqueous solution,containing 1.08 g·L^-1 sodium octane sulfonate, 1.70 g·L^-1 tetrabutyl-ammonium sulfate and 2.72 g·L^-1 potassium dihydrogen phosphate,was used as the mobile phase.The flow rate was 1.0 ml·min^-1,the detection wavelength was 210 nm,and the column temperature was 30 ℃.Results:The main impurities in cisplatin injection were trichloroammineplatinate and transplatin.Trichloroammineplatinate was photo-degradation and thermal degradation products of cisplatin.Transplatin was synthesis process impurity,which can also be increased by light illumination and oxidation.By using the current statutory standard,an unknown impurity was detected with the content of about 0.3%.This unknown impurity was confirmed as cisplatin monohydrate,which was an effective active ingredient and should not be controlled as an impurity.The overall content of impurities in cisplatin injection was significantly higher than that in cisplatin for injection.Conclusion:The current statutory standards are inadequate,and need to be improved.Compared with different dosage forms,the overall quality of cisplatin for injection was better than that of cisplatin injection.The major impurities were degradation impurities.The quality of drugs can be further improved through a series of measures,such as a usage of brown glass bottles and storage at a low temperature.