Development of the first sphingomyelin biomimetic stationary phase for immobilized artificial membrane (IAM) chromatography

Abstract

A prototype sphingomyelin stationary phase for Immobilized Artificial Membrane (IAM) chromatography was synthesized by an ultra-short, solid-phase inspired methodology, in which an oxidative release monitoring strategy played a vital role. Evaluated in a proof-of-concept model for blood-brain barrier passage, partial least squares regression demonstrated its potential as an in vitro prediction tool.

Predicting the Blood-Brain Barrier Permeability of New Drug-Like Compounds via HPLC with Various Stationary Phases

“…The octadecylsilyl (ODS) stationary phase provides a fast approach, but immobilized artificial membranes (IAMs) are more similar to the membranes of eukaryotic cells and therefore better mimic biological systems [10][11][12]. Artificial membranes are more similar to biological systems because they anchor synthetic phosphatidylcholine analogues to silica [13][14][15][16][17][18]. Cholesterol is one of the major components of many eukaryotic membranes and it seems highly likely that cholesterol immobilized on silica would offer similar possibilities.…”

Analytical methods for studying drug–biomembrane interactions

“…43,44 However, it would seem that the results obtained with these latter techniques can be effi caciously compared to the IAM interaction pattern only for strictly structure-related classes of compounds. 45,46 More recently, other biomimetic stationary phases have been developed, such as α 1 -acid glycoprotein or albumin derivatized surfaces, the latest being a sphingomyelin-based biomimetic stationary phase, 47 thus widening the application of biochromatography as a reliable tool for investigating and predicting the interaction of different kinds of drugs with cells, biochemical systems and biological barriers. 47,48 Biopartitioning chromatography (BPC) is another advance in this fi eld.…”

“…45,46 More recently, other biomimetic stationary phases have been developed, such as α 1 -acid glycoprotein or albumin derivatized surfaces, the latest being a sphingomyelin-based biomimetic stationary phase, 47 thus widening the application of biochromatography as a reliable tool for investigating and predicting the interaction of different kinds of drugs with cells, biochemical systems and biological barriers. 47,48 Biopartitioning chromatography (BPC) is another advance in this fi eld. In this technique, a chromatographic method is combined with biomembrane-mimetic structures such as PL monolayers or vesicles, micelles, niosomes, microemulsions, and so on.…”

Preparation of a biomimetic polyphosphorylcholine monolithic column for immobilized artificial membrane chromatography

“…Then the precipitate was purified by flash column chromatography on silica gel (CH 2 C1 2 /MeOH/H 2 (m, 16H). 13 …”

“…Therefore, it is of great interest to develop a novel preparation process of IAM stationary phases. Recently, Verzele et al prepared a sphingomyelin functionalized IAM column using the amide to substitute the esters of IAM.PC through a solid phase synthesis method for the first time [13], which not only enhanced column lifetime and reliability of IAM columns but also provided an in vitro prediction model for blood-brain barrier permeability of drugs. In addition to the traditional covalent immobilization strategies, a few of the non-covalent immobilization methods have also been reported.…”