Abstract：
Near UV and visible light photodegradation can target therapeutic proteins during manufacturing and storage. While the underlying photodegradation pathways are frequently not well-understood, one important aspect of consideration is the formulation, specifically the formulation buffer. Citrate is a common buffer for biopharmaceutical formulations, which can complex with transition metals, such as Fe(III). In an aqueous solution, the exposure of such complexes to light leads to the formation of the carbon dioxide radical anion (•CO2-), a powerful reductant. However, few studies have characterized such processes in solid formulations. Here, we show that solid citrate formulations containing Fe(III) lead to the photochemical formation of •CO2-, identified through DMPO spin trapping and HPLC-MS/MS analysis. Factors such as buffers, the availability of oxygen, excipients, and manufacturing processes of solid formulations were evaluated for their effect on the formation of •CO2- and other radicals such as •OH.
摘要：
近UV和可见光光降解可以在制造和储存期间靶向治疗性蛋白质。虽然潜在的光降解途径经常没有被很好地理解，考虑的一个重要方面是制定，特别是制剂缓冲液。柠檬酸盐是生物药物制剂的常用缓冲剂,可以与过渡金属络合，如Fe(III)。在水溶液中，这种络合物暴露于光导致形成二氧化碳自由基阴离子（•CO2-），一种强大的还原剂。然而,很少有研究在固体制剂中表征这样的过程。这里,我们表明，含有Fe（III）的固体柠檬酸盐配方导致光化学形成•CO2-，通过DMPO自旋捕获和HPLC-MS/MS分析鉴定。缓冲等因素，氧气的可用性，赋形剂,和固体制剂的制造过程被评价它们对形成•CO2-和其他自由基如•OH的影响。
