Interactions of Polyphenols with Immobilized Artificial Membrane and Human Serum Albumin Determined by High Performance Liquid Chromatography

Within recent years, a promising new field of chromatography has opened up with immobilization of phospholipids and human serum albumin in columns and their use in prediction of drug candidates' pharmacokinetics. It is important to investigate early in the drug discovery both the oral absorption of new drug and the extent to which it binds to plasma proteins. In the last few decades plant polyphenols became very popular phytochemicals due to their presumed role in the prevention of various degenerative diseases, such as various types of cancer and cardiovascular diseases [1]. Until recently, relatively little information was available on their absorption and subsequent distribution and excretion in humans. The aim of our work was to investigate interactions of 30 polyphenols with immobilized artificial membrane (IAM) and human serum albumin (HSA) by high performance liquid chromatography in order to predict their oral absorption and plasma protein binding. The interaction of polyphenols with IAM was evaluated by using IAM.PC.DD 2 column. The solvent system (methanol-buffer) was used as a mobile phase with a varying content of organic modifier. The interaction of polyphenols with phospholipids was expressed as the logarithm of capacity factor, which was in the range from 1.345 to 3.581. The HSA binding values were derived from the gradient retention times using Chiral HSA column with buffer and 2-propanol as a mobile phase. The binding of polyphenols to HSA was in the range from 81.8% to 99.8%. Furthermore, the correlation between experimental and pharmacokinetic parameters predicted by different computer programs was considered in order to establish relationship between chromatographic behavior and predicted parameters. According to our research, chromatographic parameters proved to be useful for evaluation of lipophilicity, oral absorption and plasma protein binding properties of investigated polyphenols.

Reference: 1. Havsteen, B. H. (2002) Pharmacol. Ther. 96: 67–202.