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.

中文翻译：

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药用辅料通过近紫外光和可见光增强药用缓冲液中铁依赖性光降解：柠檬酸盐缓冲液中抗氧化剂甲硫氨酸反应的酪氨酸修饰

目的

评估赋形剂（包括糖和氨基酸）对近紫外线和可见光诱导的药物缓冲液中光降解反应的影响。

方法

柠檬酸盐或醋酸盐缓冲液，含有 1 或 50 μM Fe ³⁺，模型肽蛋氨酸脑啡肽 (MEn)、亮氨酸脑啡肽 (LEn) 或 proctolin 肽 (ProP)，在常用氨基酸或糖的存在下，照片- 用近紫外线或可见光照射。通过反相 HPLC 和 HPLC-MS/MS 分析氧化产物。

结果

糖类甘露醇、蔗糖和海藻糖以及氨基酸 Arg、Lys 和 His 显着促进肽 Met 氧化为肽 Met 亚砜。这些赋形剂不会增加过氧化氢的产量，这表明其他氧化剂如过氧自由基负责肽 Met 的氧化。添加游离 Met 会减少肽 Met 的氧化，但在柠檬酸盐缓冲液中，会导致将 Met 氧化产物添加到目标肽的 Tyr 残基上。

结论

常用赋形剂可增强模型肽中氨基酸的光诱导氧化。