Pharmaceutical Excipients Enhance Iron-Dependent Photo-Degradation in Pharmaceutical Buffers by near UV and Visible Light: Tyrosine Modification by Reactions of the Antioxidant Methionine in Citrate Buffer.
Pharm Res
; 38(5): 915-930, 2021 May.
Article
em En
| MEDLINE
| ID: mdl-33881737
ABSTRACT
PURPOSE:
To evaluate the effect of excipients, including sugars and amino acids, on photo-degradation reactions in pharmaceutical buffers induced by near UV and visible light.METHODS:
Solutions of citrate or acetate buffers, containing 1 or 50 µM Fe3+, the model peptides methionine enkephalin (MEn), leucine enkephalin (LEn) or proctolin peptide (ProP), in the presence of commonly used amino acids or sugars, were photo-irradiated with near UV or visible light. The oxidation products were analyzed by reverse-phase HPLC and HPLC-MS/MS.RESULTS:
The sugars mannitol, sucrose and trehalose, and the amino acids Arg, Lys, and His significantly promote the oxidation of peptide Met to peptide Met sulfoxide. These excipients do not increase the yields of hydrogen peroxide, suggesting that other oxidants such as peroxyl radicals are responsible for the oxidation of peptide Met. The addition of free Met reduces the oxidation of peptide Met, but, in citrate buffer, causes the addition of Met oxidation products to Tyr residues of the target peptides.CONCLUSIONS:
Commonly used excipients enhance the light-induced oxidation of amino acids in model peptides.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
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Ácido Cítrico
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Excipientes
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Ferro
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Antioxidantes
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article