Ong S, Liu H, Pidgeon C
Department of Medicinal Chemistry, School of Pharmacy, Purdue University, West Lafayette, IN 47907, USA.
J Chromatogr A. 1996 Mar 29;728(1-2):113-28. doi: 10.1016/0021-9673(95)00837-3.
Immobilized artificial membranes (IAMs) are chromatographic surfaces prepared by covalently immobilizing cell membrane phospholipids to solid surfaces at monolayer densities. IAM surfaces mimic fluid cell membranes. For 23 structurally unrelated compounds, solute capacity factors [log (k'IAM)] measured on IAM columns correlate very well with the solute equilibrium partition coefficients [log (Km)] measured in fluid liposome systems (r = 0.907). This indicates that solute partitioning between the IAM bonded phase and the aqueous mobile phase is similar to the solute partitioning between liposomes and the aqueous phase. IAMs also predicted oral drug absorption in mice and drug permeability through Caco-2 cells. IAM chromatography is experimentally simple and large volume screening of experimental compounds for drug absorption is possible. Solute retention on IAMs was found to be dominated by a partitioning mechanism. The structural requirements for HPLC bonded phases to predict solute-membrane partitioning are briefly discussed.
固定化人工膜（IAMs）是通过将细胞膜磷脂以单层密度共价固定在固体表面而制备的色谱表面。IAM表面模拟流体细胞膜。对于23种结构不相关的化合物，在IAM柱上测得的溶质容量因子[log(k'IAM)]与在流体脂质体系统中测得的溶质平衡分配系数[log(Km)]具有很好的相关性（r = 0.907）。这表明溶质在IAM键合相和水相流动相之间的分配类似于溶质在脂质体和水相之间的分配。IAMs还可预测小鼠口服药物的吸收以及药物透过Caco-2细胞的情况。IAM色谱实验操作简单，可对实验化合物进行大体积筛选以评估药物吸收情况。发现溶质在IAMs上的保留主要由分配机制主导。本文简要讨论了用于预测溶质-膜分配的高效液相色谱键合相的结构要求。
