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

Abstract

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 (•CO2−), a powerful reductant, and other photoproducts such as aldehydes and His-derived radicals. The generation of •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.