Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability. However, some excipients are prone to degradation during repeated use and/or improper storage, and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored, affecting the stability of biopharmaceuticals. In this study, we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry (GC-MS). The other polyol excipient, mannitol, was much more stable than glycerol. The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide, thymopentin, were also evaluated. The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol, compared to 95.8% in other formulations after the stress test. Most glycerol impurities (i.e., aldehydes and ketones) reacted with thymopentin, affecting the stability of thymopentin formulations. In conclusion, this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage. Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

使用多种赋形剂配制生物药物以保持其储存稳定性。然而，一些辅料在重复使用和/或储存不当的过程中容易发生降解，其降解产生的杂质很容易被最终用户忽视，通常没有严格监控，影响生物制药的稳定性。在本研究中，我们评估了多元醇赋形剂甘油在重复使用和不当储存期间的降解曲线，并使用气相色谱质谱 (GC-MS) 鉴定了前所未有的环状缩酮杂质。另一种多元醇赋形剂甘露醇比甘油稳定得多。还评估了降解的甘油和甘露醇对模型生物药物五肽胸腺五肽稳定性的影响。胸腺五肽含量仅为66。在压力测试后，在含有降解甘油的胸腺五肽制剂中为 4%，而在其他制剂中为 95.8%。大多数甘油杂质（即醛和酮）与胸腺五肽反应，影响胸腺五肽制剂的稳定性。综上所述，这项工作表明，应更多地关注辅料在重复使用和储存过程中的质量变化。制造商在真实或加速条件下对辅料稳定性进行额外测试将有助于避免意外和痛苦的结果。这项工作表明，应更多地关注辅料在重复使用和储存过程中的质量变化。制造商在真实或加速条件下对辅料稳定性进行额外测试将有助于避免意外和痛苦的结果。这项工作表明，应更多地关注辅料在重复使用和储存过程中的质量变化。制造商在真实或加速条件下对辅料稳定性进行额外测试将有助于避免意外和痛苦的结果。