Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption

Dina Shokry, Laura Waters, Gareth Parkes, John C. Mitchell

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1 Citation (Scopus)

Abstract

Micellar liquid chromatography is a popular method used in the determination of a compound's lipophilicity. This study describes the use of the obtained micelle–water partition coefficient (log P mw) by such a method in the prediction of human intestinal absorption (HIA). As a result of the close resemblance of the novel composition of the micellar mobile phase to that of physiological intestinal fluid, prediction was deemed to be highly successful. The unique micellar mobile phase consisted of a mixed micellar mixture of lecithin and six bile salts, i.e. a composition matching that found in the human intestinal environment, prepared in ratios resembling those in the intestine. This is considered to be the first method to use a physiological mixture of biosurfactants in the prediction of HIA. As a result, a mathematical model with high predictive ability (R 2 PRED = 81%) was obtained using multiple linear regression. The micelle–water partition coefficient (log P mw) obtained from micellar liquid chromatography was found to be a successful tool for prediction where the final optimum model included log P mw and polar surface area as key descriptors with high statistical significance for the prediction of HIA. This can be attributed to the nature of the mobile phase used in this study which contains the lecithin–bile salt complex, thus forming a bilayer system and therefore mimicking absorption across the intestinal membrane.

Original languageEnglish
Article numbere4351
Number of pages9
JournalBiomedical Chromatography
Volume32
Issue number12
Early online date30 Jul 2018
DOIs
Publication statusPublished - Dec 2018

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Intestinal Absorption
Liquid chromatography
Liquid Chromatography
Lecithins
Bile Acids and Salts
Intestines
Linear Models
Chemical analysis
Theoretical Models
Linear regression
Salts
Membranes
Mathematical models
Fluids

Cite this

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title = "Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption",
abstract = "Micellar liquid chromatography is a popular method used in the determination of a compound's lipophilicity. This study describes the use of the obtained micelle–water partition coefficient (log P mw) by such a method in the prediction of human intestinal absorption (HIA). As a result of the close resemblance of the novel composition of the micellar mobile phase to that of physiological intestinal fluid, prediction was deemed to be highly successful. The unique micellar mobile phase consisted of a mixed micellar mixture of lecithin and six bile salts, i.e. a composition matching that found in the human intestinal environment, prepared in ratios resembling those in the intestine. This is considered to be the first method to use a physiological mixture of biosurfactants in the prediction of HIA. As a result, a mathematical model with high predictive ability (R 2 PRED = 81{\%}) was obtained using multiple linear regression. The micelle–water partition coefficient (log P mw) obtained from micellar liquid chromatography was found to be a successful tool for prediction where the final optimum model included log P mw and polar surface area as key descriptors with high statistical significance for the prediction of HIA. This can be attributed to the nature of the mobile phase used in this study which contains the lecithin–bile salt complex, thus forming a bilayer system and therefore mimicking absorption across the intestinal membrane.",
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