Department of Pharmaceutical Chemistry, University of Kansas, 2093 Constant Avenue, Lawrence, KS 66047, USA.
Department of Pharmaceutical Chemistry, University of Kansas, 2093 Constant Avenue, Lawrence, KS 66047, USA.
J Pharm Sci. 2024 Sep;113(9):2683-2687. doi: 10.1016/j.xphs.2024.06.021. Epub 2024 Jul 21.
In recent studies we have reported on the near-UV light-induced degradation of iron complexes of various pharmaceutical excipients, such as Fe(III)-citrate and Fe(III)-amino acid complexes. Mechanistic studies revealed a common photo-degradation pattern, i.e. the formation of carbon dioxide radical anion, a potent reducing agent, via an alkoxyl/amino radical intermediate generated by light-induced ligand-to-metal charge transfer (LMCT) involving α-hydroxycarboxylates or amino acids. Herein, we confirm the proposed general photo-degradation pathways through the study of the iron complexes of other α-hydroxycarboxylates that may be present in protein formulations, such as lactate and glycolate. The results indicate that lactate generates even higher yields of CO as compared to citrate, suggesting a significant potential of lactate for the promotion of photo-degradation in pharmaceutical formulations.
在最近的研究中，我们报道了各种药物赋形剂的铁配合物在近紫外光下的降解，如柠檬酸铁(III)和氨基酸铁(III)配合物。机理研究揭示了一种常见的光降解模式，即通过涉及α-羟基羧酸或氨基酸的配体到金属电荷转移（LMCT）产生的烷氧基/氨基自由基中间体，形成二氧化碳自由基阴离子，一种有效的还原剂。在此，我们通过研究可能存在于蛋白质制剂中的其他α-羟基羧酸的铁配合物，如乳酸盐和乙醇酸盐，证实了所提出的一般光降解途径。结果表明，与柠檬酸相比，乳酸盐产生的 CO 产量更高，这表明乳酸盐在药物制剂的光降解中具有显著的促进潜力。
