Enhanced chemical stability of an immobilized artificial membrane stationary phase achieved via atom-transfer radical...

Immobilized artificial membrane (IAM) chromatography is a vital technique for studying drug-biomembrane interactions, predicting drug permeability, and facilitating drug screening. However, its broader application is hindered by the limited commercial availability of IAM columns, their susceptibility to aging or premature failure, and the complexity of preparation process. In this study, a novel strategy for fabricating IAM stationary phases was developed via atom transfer radical polymerization (ATRP). Using 12-methacryloyl dodecylphosphatidylcholine (MDPC) as a phospholipid functional monomer, this proposed approach enables the in-situ growth of a uniform phospholipid polymer coating on silica surfaces, which not only effectively protects the silica matrix from aggressive acidic or basic mobile phases, but also effectively simulates the phospholipid microenvironment of cell membranes. The resulting IAM stationary phase showed excellent chemical stability over a wide pH range (2.0∼10.0). The evaluation of 62 drugs revealed a strong correlation (Spearman correlation coefficient = 0.83) between the CHI IAM values obtained from our self-prepared IAM stationary phase and a commercial IAM column. This close agreement demonstrates that our novel phase can reliably mimic commercial IAM columns, thereby showing its potential applicability in key pharmaceutical scenarios, such as predicting drug transmembrane permeability, for which commercial IAM columns are standardly employed. This provides a new idea for the development of high-performance bionic chromatographic materials and lays an important foundation for the subsequent research and development of different types of IAM stationary phases.