Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

AlphaLogD Determination: A New Generation Reversed-Phase HPLC Method to Measure Lipophilicity on Neutral and Basic Small and Beyond-Rule-of-Five Compounds

Version 1 : Received: 18 February 2021 / Approved: 23 February 2021 / Online: 23 February 2021 (14:07:42 CET)

How to cite: Katz, D.; Fike, K.; Longenberger, J.; Placko, S.; Philippe-Venec, L.; Chervenak, A. AlphaLogD Determination: A New Generation Reversed-Phase HPLC Method to Measure Lipophilicity on Neutral and Basic Small and Beyond-Rule-of-Five Compounds. Preprints 2021, 2021020514 (doi: 10.20944/preprints202102.0514.v1). Katz, D.; Fike, K.; Longenberger, J.; Placko, S.; Philippe-Venec, L.; Chervenak, A. AlphaLogD Determination: A New Generation Reversed-Phase HPLC Method to Measure Lipophilicity on Neutral and Basic Small and Beyond-Rule-of-Five Compounds. Preprints 2021, 2021020514 (doi: 10.20944/preprints202102.0514.v1).

Abstract

Lipophilicity can be measured with different methods, such as Shake-Flask or liquid chromatography. HPLC presents the advantage of overcoming solubility issues and therefore extending the range of lipophilicity to high values. A specific HPLC method, called ELogD, had been developed 20 years ago on a C16-amide stationary phase, enhancing hydrophobic and hydrogen bond interactions to mimic octanol-water partition. The emergence of novel stationary phases added to the need for a less complex mobile phase has led to the development of a new HPLC assay called alphaLogD, applicable to neutral and basic compounds at pH 7.4, that combines superficially porous particles, a high number of equilibriums between solutes and stationary phase, and results in a lower number of isocratic methods to determine the logk’w at a higher throughput. Statistical studies have been run to successfully evaluate the alphaLogD method compared to the Shake-Flask method and to allow this lipophilicity measurement into the so-called Beyond-Rule-of-5-molecules space.

Subject Areas

High Performance Liquid Chromatography; Superficially Porous Particle; Shake-Flask method; Lipophilicity; Beyond-Rule-of-5

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