Shokry, Dina S., Waters, Laura J., Parkes, Gareth M. B. and Mitchell, John C. ORCID: 0000-0003-2945-3292 (2018) Incorporating physiologically relevant mobile phases in micellar liquid chromatography for the prediction of human intestinal absorption. Biomedical Chromatography, 32 (12):e4351. ISSN 0269-3879 (Print), 1099-0801 (Online) (doi:https://doi.org/10.1002/bmc.4351)

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Abstract

Micellar liquid chromatography (MLC) is a popular method used in the determination of a compounds lipophilicity. This study describes the use of the obtained micelle/water partition coefficient (log Pmw) 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 (R2PRED= 81 %) was obtained using multiple linear regression. The micelle/water partition coefficient (log Pmw) obtained from MLC was found to be a successful tool for prediction where the final optimum model included (log Pmw) and polar surface area (PSA) 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 therefore mimicking absorption across the intestinal membrane.

Item Type:	Article
Additional Information:	© 2018 The Authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Uncontrolled Keywords:	MLC; HIA; bile salt; Pmw; lipophilicity
Subjects:	Q Science > QD Chemistry R Medicine > RM Therapeutics. Pharmacology
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI) Faculty of Engineering & Science > Medway Centre for Pharmaceutical Science Faculty of Engineering & Science > Medway Centre for Pharmaceutical Science > Pharmaceutical and Medicinal Science Research Group
Last Modified:	18 Apr 2019 12:00
URI:	http://gala.gre.ac.uk/id/eprint/21176

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