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目的:通过多种分析方法分析国内外两种剂型的近效期重组人生长激素(rhGH)有关物质的组成和含量。方法:采用2010版《中华人民共和国药典》二部rhGH各论下的分子排阻色谱、反相色谱及等电聚焦电泳等方法,结合基质辅助激光解吸附电离飞行时间质谱(MALDI-TOF MS)对16批注射用rhGH及3批rhGH注射液进行了高分子蛋白质及有关物质的分析。结果:2种剂型rhGH高分子蛋白的含量及增长模式较为相近,效期结束时增加了约1倍,而总有关物质特别是脱酰胺rhGH的含量则有较大差异。注射用rhGH的总有关物质含量增长了约1.5倍。国内企业近效期rhGH注射液的总有关物质含量增长了约5倍,而国外企业增长了约9倍,均接近或超过注射用rhGH相关物质13.0%的限值,其中最主要的有关物质为脱酰胺rhGH。结论:rhGH在液态剂型中更容易产生有关物质
OBJECTIVE: To analyze the composition and content of near-term recombinant human growth hormone (rhGH) -related substances at home and abroad by a variety of analytical methods. Methods: The molecular weight exclusion chromatography (rhGH), RP-HPLC and isoelectric focusing electrophoresis were used in the 2010 edition of “The People’s Republic of China Pharmacopoeia”. Combined with matrix-assisted laser desorption / ionization time of flight mass spectrometry (MALDI-TOF MS) 16 batches of injection of rhGH and 3 batches of rhGH injection of polymer proteins and related substances were analyzed. Results: The contents of two kinds of rhGH macromolecule protein and their growth pattern were similar, and the content of rhGH protein increased about 1 time at the end of the expiration period, while the content of total related substances, especially deamidated rhGH, was quite different. The total amount of related substances in rhGH for injection increased about 1.5 times. The total content of the related substances of rhGH injection increased by about 5 times during the near term in domestic enterprises, while the foreign enterprises increased by about 9 times, all approaching or exceeding the limit of 13.0% of the rhGH-related substances for injection. The most important related substances were Deamidation rhGH. CONCLUSIONS: rhGH is more likely to produce related substances in liquid dosage forms