Institute of Chemical Technologies and Analytics, Vienna University of Technology, Getreidemarkt 9/164-IAC, A-1060 Vienna, Austria.
J Pharm Biomed Anal. 2010 Aug 1;52(4):432-7. doi: 10.1016/j.jpba.2010.01.017. Epub 2010 Jan 18.
One of the most prominent polymer group applied for drug conjugation is poly(ethylene) glycol (PEG). Since drug production is subjected to strict restrictions on the part of the FDA and EMEA, also PEG has to be characterized accurately. Particularly its molecular mass distribution (MMD) and polydispersity can result in unrequested inhomogeneous final products. Therefore evaluation of PEG before applying it to drug conjugation is essential. In this study a new analytical method for size and molecular mass determination based on electrophoretic mobility called GEMMA is used to characterize linear PEGs with two differing terminating functional groups. To confirm the data acquired by GEMMA a second, well-established method for molecular weight determination, MALDI-TOF MS (matrix-assisted laser desorption ionization time-of-flight mass spectrometry), was applied. Utilizing these two analytical approaches four monomethoxylated PEG-succinimidyl succinate (mPEG-SS) derivatives were investigated in terms of polydispersity and MMD. Although based on differing principles, both analytical methods yield comparable results. All obtained MMD maxima for the mPEG-SS batches lie within the company stated specifications, MMD+/-10% (based on MALDI-TOF MS data). For mPEG-SS 2K a polydispersity of 1.02 and for mPEG-SS 5K, 10K and 20K a polydispersity of 1.01 were determined from GEMMA as well as from MALDI-TOF MS data and are in agreement with the company's data (based on GPC data), namely 1.05-1.10.
用于药物偶联的最突出的聚合物之一是聚乙二醇（PEG）。由于药物生产受到 FDA 和 EMEA 的严格限制，PEG 也必须进行准确的表征。特别是其分子量分布（MMD）和多分散性可能导致最终产品不均匀。因此，在将 PEG 应用于药物偶联之前，对其进行评估是必不可少的。在这项研究中，使用一种称为 GEMMA 的基于电泳迁移率的新分析方法来对具有两种不同末端官能团的线性 PEG 进行大小和分子量测定。为了确认 GEMMA 获得的数据，应用了第二种经过充分验证的分子量测定方法，MALDI-TOF MS（基质辅助激光解吸电离飞行时间质谱）。利用这两种分析方法，对四种单甲氧基化聚乙二醇琥珀酰亚胺琥珀酸酯（mPEG-SS）衍生物的多分散性和 MMD 进行了研究。尽管基于不同的原理，但这两种分析方法都得出了可比的结果。所有获得的 mPEG-SS 批次的 MMD 最大值都在公司规定的规格范围内，即 MMD+/-10%（基于 MALDI-TOF MS 数据）。从 GEMMA 和 MALDI-TOF MS 数据确定 mPEG-SS 2K 的多分散性为 1.02，mPEG-SS 5K、10K 和 20K 的多分散性为 1.01，与公司数据（基于 GPC 数据）一致，即 1.05-1.10。
