Near UV light photo-degradation of histidine buffer: Mechanisms and role of Fe(III)

Pharmaceutical formulations are sensitive to light-induced degradation. Recent studies have attributed some of the light sensitivity to the presence of Fe(III), the most prevalent metal leachable from pharmaceutical containers. Histidine (His) can promote Fe(III) leaching from stainless steel, especially at elevated storage temperatures. Since there is the chance that combinations of His and Fe(III) are present in pharmaceutical formulations, we investigated the photo-degradation mechanisms of Fe(III)-containing His buffer during expsoure to near UV light. Our results indicate the formation of carbon dioxide radical anion (& BULL;CO2  ), a powerful reductant, and other photoproducts such as aldehydes and His-derived radicals. The generation of & BULL;CO2  can be promoted by increasing concentrations of Fe(III) and inhibited by the addition of the Fe(III) chelator EDTA. Mechanistically, product formation can be rationalized by photo-induced ligand-to-metal-charge-transfer (LMCT), followed by a series of radical transformations of reaction intermediates.

Automated summary

Pharmaceutical formulations are sensitive to light-induced degradation, which can be attributed to the presence of Fe(III) leachable from pharmaceutical containers. The leaching of Fe(III) from stainless steel can be promoted by histidine (His), especially at elevated storage temperatures. Our study investigates the photo-degradation mechanisms of Fe(III)-containing His buffer during exposure to near UV light, and suggests the formation of carbon dioxide radical anion and other photoproducts.