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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,4μm),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 of cisplatin injections, investigate the scientific nature of existing quality standards, discuss the existing problems and provide references for improving standards and product quality. Methods: Merck Superspher RP-select B C8 column (4 mm × 250 mm, 4 μm) was used in this study. The optimal conditions were as follows: sodium octane sulfonate 1.08 g · L -1, tetrabutylammonium sulfate 1.70 g · L -1, The aqueous solution of potassium dihydrogen phosphate 2.72 g · L-1 was used as the mobile phase at the flow rate of 1.0 mL · min -1, the detection wavelength was 210 nm and the column temperature was 30 ℃. Results: The main impurities detected in Cisplatin injection were cisplatin and transplatinum. Among them, trichloroammineplatin was light and high temperature degradation products, and trans-platinum was a synthetic process impurity and light and oxidative degradation impurities. According to the current standard test, the detection of unknown content of about 0.3% of the ingredients, confirmed as cisplatin monohydrate, is an active ingredient, should not be controlled as impurities. Cisplatin injection formulations related substance content was significantly higher than the powder injection. Conclusion: The current standards have some defects and need to be improved. Compared with different dosage forms, the overall quality of cisplatin for injection is better than that of cisplatin injection. The main impurities detected are degradation of impurities, which can be further reduced by using a series of measures such as brown glass bottle and cryogenic preservation Improve the quality of medicines