Prediction of human intestinal absorption using micellar liquid chromatography with an aminopropyl stationary phase

Dina S. Shokry, Laura J. Waters, Gareth M.B. Parkes, John C. Mitchell

Research output: Contribution to journalArticle

Abstract

The extent of human intestinal absorption (HIA) for a drug is considered to be an important pharmacokinetic parameter which must be determined for orally administered drugs. Traditional experimental methods relied upon animal testing and are renowned for being time consuming and expensive as well as being ethically unfavourable. As a result, the development of alternative methods to evaluate a drug's pharmacokinetics is crucial. Micellar liquid chromatography is considered to be one of these methods that can replace the use of animals in the prediction of HIA. In this study, the combination of an aminopropyl column with the biosurfactant sodium deoxycholate bile salt was used in the experimental determination of micelle–water partition coefficients (log P mw ) for a group of compounds. Multiple linear regression was then used for the prediction of HIA using the experimentally determined log P mw along with other molecular descriptors, leading to the construction of a model equation of R 2 = 85% and a prediction power represented by R 2 Pred. = 72%. The use of micellar liquid chromatography with an aminopropyl column in combination with sodium deoxycholate was found to be a good method for the prediction of human intestinal absorption, providing data for a far wider range of compounds compared with previous studies.

LanguageEnglish
Article numbere4515
JournalBiomedical Chromatography
Volume33
Issue number7
Early online date27 Feb 2019
DOIs
Publication statusPublished - 1 Jul 2019

Fingerprint

Intestinal Absorption
Liquid chromatography
Liquid Chromatography
Deoxycholic Acid
Pharmacokinetics
Animals
Pharmaceutical Preparations
Micelles
Bile Acids and Salts
Linear regression
Linear Models
Water
Testing

Cite this

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title = "Prediction of human intestinal absorption using micellar liquid chromatography with an aminopropyl stationary phase",
abstract = "The extent of human intestinal absorption (HIA) for a drug is considered to be an important pharmacokinetic parameter which must be determined for orally administered drugs. Traditional experimental methods relied upon animal testing and are renowned for being time consuming and expensive as well as being ethically unfavourable. As a result, the development of alternative methods to evaluate a drug's pharmacokinetics is crucial. Micellar liquid chromatography is considered to be one of these methods that can replace the use of animals in the prediction of HIA. In this study, the combination of an aminopropyl column with the biosurfactant sodium deoxycholate bile salt was used in the experimental determination of micelle–water partition coefficients (log P mw ) for a group of compounds. Multiple linear regression was then used for the prediction of HIA using the experimentally determined log P mw along with other molecular descriptors, leading to the construction of a model equation of R 2 = 85{\%} and a prediction power represented by R 2 Pred. = 72{\%}. The use of micellar liquid chromatography with an aminopropyl column in combination with sodium deoxycholate was found to be a good method for the prediction of human intestinal absorption, providing data for a far wider range of compounds compared with previous studies.",
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Prediction of human intestinal absorption using micellar liquid chromatography with an aminopropyl stationary phase. / Shokry, Dina S.; Waters, Laura J.; Parkes, Gareth M.B.; Mitchell, John C.

In: Biomedical Chromatography, Vol. 33, No. 7, e4515, 01.07.2019.

Research output: Contribution to journalArticle

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