柱串联凝胶色谱分离表征多分散聚乙二醇羧酸衍生物的方法研究

Separation and Characterization of Polyethylene Glycol Carboxylic Acid Derivatives by Gel Chromatography with Tandem Gel Columns

药用聚乙二醇(PEG)由于具有多分散特性而导致其衍生物之间的分离表征极其困难。常规的基于分子排阻(SEC)的凝胶色谱对于相同平均分子量(M_(n))的PEG衍生物很难实现良好的分离效果。对平均分子量为2000和5000的直链聚乙二醇(PEG)及其羧酸衍生物进行了色谱分析。在低离子强度下,采用示差折光检测器和3种OHpark KF型色谱柱串联对一系列多分散PEG衍生物进行了分离表征,解决了聚乙二醇及其羧酸衍生物分离表征难题。结果表明,这些PEG衍生物在OHpark KF色谱柱上的保留机制主要是离子交换相互作用。当流动相中的盐浓度增加时,保留体积减小,并且保留体积和保留时间随着洗脱液的溶剂比例以及柱温的变化而变化。此外,PEG链的链长度和末端基团对PEG化合物的色谱行为也会产生明显影响。

Due to the polydispersion characteristics of medicinal polyethylene glycol(PEG),it is extremely difficult to separate and characterize PEG derivatives.Conventional gel chromatography based on size exclusion chromatography(SEC)is difficult to achieve a good separation effect for PEG derivatives with the same average molecular weight(M_(n)).This research describes achromatographic analysis of straight-chain polyethylene glycol(PEG)and their carboxyl-substituted derivatives(M_(n)=2000 or 5000).A series of polydisperse PEG derivatives were separated by tandem OHpark KF column under low ionic strength with refractive index detection(RID).The problem inseparation and characterization of carboxylic functionalized and unfunctionalized polyethylene glycol(PEG)due to its polydispersion property was solved.The results showed that the retention mechanism of these PEG derivatives on the OHpark KF column was mainly the ion exchange interactions,because the retention volume decreased with the increase of salt concentration in the mobile phase,and the retention time and volume changed with the solvent content and column temperature.Moreover,the size and the end functional groups of the PEG chain also have an obvious effect on the chromatographic behavior of PEG compounds.