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

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 c...

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Autores principales: Shokry, Dina S., Waters, Laura J., Parkes, Gareth M. B., Mitchell, John C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282790/
https://www.ncbi.nlm.nih.gov/pubmed/30062715
http://dx.doi.org/10.1002/bmc.4351
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author Shokry, Dina S.
Waters, Laura J.
Parkes, Gareth M. B.
Mitchell, John C.
author_facet Shokry, Dina S.
Waters, Laura J.
Parkes, Gareth M. B.
Mitchell, John C.
author_sort Shokry, Dina S.
collection PubMed
description 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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spelling pubmed-62827902018-12-11 Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption Shokry, Dina S. Waters, Laura J. Parkes, Gareth M. B. Mitchell, John C. Biomed Chromatogr Research Articles 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. John Wiley and Sons Inc. 2018-08-16 2018-12 /pmc/articles/PMC6282790/ /pubmed/30062715 http://dx.doi.org/10.1002/bmc.4351 Text en © 2018 The Authors. Biomedical Chromatography published by John Wiley & Sons, Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Articles
Shokry, Dina S.
Waters, Laura J.
Parkes, Gareth M. B.
Mitchell, John C.
Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption
title Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption
title_full Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption
title_fullStr Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption
title_full_unstemmed Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption
title_short Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption
title_sort incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282790/
https://www.ncbi.nlm.nih.gov/pubmed/30062715
http://dx.doi.org/10.1002/bmc.4351
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