1University of Zagreb, Faculty of Pharmacy and Biochemistry Department of Pharmaceutical Analysis, 10000 Zagreb, Croatia.
2Clinical Hospital Zagreb Department of Gastroenterology, 10000 Zagreb Croatia.
Acta Pharm. 2023 Dec 26;73(4):709-721. doi: 10.2478/acph-2023-0044. Print 2023 Dec 1.
Size exclusion chromatography (SEC) has become a powerful tool for analysing size variants of biologic drugs in their native form. Modern SEC can be defined by the use of chromatographic columns packed with sub-3 µm particles, allowing an increase in method throughput compared to that of conventional SEC. We performed the forced degradation study of adalimumab, the first genetically engineered fully humanised immunoglobulin G1 monoclonal antibody, and evaluated tha possibilities of an advanced SEC column packed with sub-3 µm particles for elucidation of the degradation pathway. Our results revealed the main adalimumab degradation products to be antibody fragments. Acidic and basic conditions had the most intensive effect on the degradation of the adalimumab while the drug exhibits relative stability under thermal and photolytic stress conditions. The AGREE and AGREEprep calculators were used for the evaluation of the environmental performance of the forced degradation procedure. The results of the green score evaluation are presented as round pictograms with a circle in the centre that shows the overall score of 0.81 and 0.61, respectively. Both pictograms are highlighted in green, indicating the eco-friendly conditions.
体积排阻色谱法（SEC）已成为分析生物药物天然形式的大小变异体的有力工具。现代 SEC 可定义为使用填充有亚 3µm 颗粒的色谱柱，与传统 SEC 相比，方法通量得到了提高。我们对阿达木单抗（首个基因工程全人源化 IgG1 单克隆抗体）进行了强制降解研究，并评估了使用填充有亚 3µm 颗粒的先进 SEC 柱阐明降解途径的可能性。我们的结果表明，阿达木单抗的主要降解产物为抗体片段。在酸性和碱性条件下，阿达木单抗的降解作用最强，而在热和光解应激条件下，药物表现出相对稳定性。AGREE 和 AGREEprep 计算器用于评估强制降解程序的环境性能。绿色评分评估的结果以圆形象形图表示，中间的圆圈显示总分为 0.81 和 0.61。两个象形图均用绿色突出显示，表示环保条件。
