Fast monolithic micellar liquid chromatography: an alternative drug permeability assessing method for high-throughput screening.
Several methods estimating the partitioning over biological membranes and thus the biological activity of potential oral drug molecules have been developed and are described in the literature. A previous study suggested that fast micellar liquid chromatography on a monolithic column could be one of them. For a set of diverse pharmaceuticals, retention by this fast chromatographic method was determined, besides other parameters also thought or established to describe oral permeability or absorption, e.g., from the Caco-2 permeability method. In view of a high-throughput determination of membrane permeability, a study was made of which information fast micellar liquid chromatography is providing and to what degree this system can replace other methods, i.e., deliver similar information. The retention with this fast method, which is mainly based on hydrophobic interactions, proved useful to sort substances into classes of Caco-2 and percent intestinal absorption.
Detroyer
A
A
Department of Pharmaceutical and Biomedical Analysis, Pharmaceutical Institute, Vrije Universiteit Brussel-VUB, Laarbeeklaan 103, B-1090 Brussels, Belgium.
Stokbroekx
S
S
Bohets
H
H
Lorreyne
W
W
Timmerman
P
P
Verboven
P
P
Massart
D L
DL
Vander Heyden
Y
Y
D018938:Caco-2 Cells; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007408:Intestinal Absorption / Q000502:physiology; D008567:Membranes, Artificial; D008823:Micelles; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D008567:Membranes, Artificial; D008823:Micelles; D004364:Pharmaceutical Preparations