Biomolecular Formulation and Characterization Sciences, UCB, Slough SL3WE, UK.
Biomolecular Formulation and Characterization Sciences, UCB, Slough SL3WE, UK.
Eur J Pharm Biopharm. 2021 Mar;160:35-41. doi: 10.1016/j.ejpb.2021.01.011. Epub 2021 Jan 26.
The correct choice of formulation buffer is a critical aspect of drug development and is chosen primarily to improve the stability of a protein therapeutic and protect against degradation. Amino acids are frequently incorporated into formulation buffers. In this study we have identified and characterized light induced cross-links between the side chain of histidine residues in an IgG4 monoclonal antibody and different amino acids commonly used in formulation buffers. These reactions have the potential to impact the overall product quality of the drug. The structure of each cross-link identified was elucidated using high performance liquid chromatography (HPLC) hyphenated to tandem mass spectrometry (MS/MS) with higher energy collisional dissociation (HCD). Furthermore, we speculate on the role of amino acids in formulation buffers and their influence on mAb stability. We theorize that whilst the adduction of formulation buffer amino acids could have a negative impact on product quality, it may protect against other pathways of photo-degradation.
正确选择制剂缓冲液是药物开发的一个关键方面，主要是为了提高蛋白质治疗药物的稳定性并防止降解。氨基酸经常被纳入制剂缓冲液中。在这项研究中，我们已经鉴定并表征了 IgG4 单克隆抗体中组氨酸残基侧链与制剂缓冲液中常用的不同氨基酸之间的光诱导交联。这些反应有可能影响药物的整体产品质量。使用高效液相色谱（HPLC）与串联质谱（MS/MS）联用（高能量碰撞解离（HCD））阐明了每种鉴定的交联结构。此外，我们还推测了氨基酸在制剂缓冲液中的作用及其对 mAb 稳定性的影响。我们推测，虽然制剂缓冲液氨基酸的加成可能对产品质量产生负面影响，但它可能会防止其他光降解途径。
