Generic placeholder image

Combinatorial Chemistry & High Throughput Screening

Editor-in-Chief

ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

A Novel Method for High Throughput Lipophilicity Determination by Microscale Shake Flask and Liquid Chromatography Tandem Mass Spectrometry

Author(s): Baiwei Lin and Joseph H. Pease

Volume 16 , Issue 10 , 2013

Page: [817 - 825] Pages: 9

DOI: 10.2174/1386207311301010007

Price: $65

Abstract

Modern small molecule drug design requires the optimization of not only the binding characteristics of the molecule but also its physicochemical properties for ADMET performance. A key physical property is lipophilicity and medicinal chemists need rapid access to high quality data in order to drive their decision making. Traditionally lipophilicity (log D) measurements are performed with a shake flask method and UV determination. This method suffers from low sensitivity and is not easily converted to a high throughput format. Over the past decade, several groups have taken different approaches to improve this assay, including replacing the shake flask method with one that utilizes reverse phase HPLC. Here we describe a new microscale shake flask method that utilizes UPLC–MS/MS to achieve increased throughput, sensitivity and accuracy. Approaches for assessing data quality are also described. This platform technology only requires micrograms of compound and is routinely used by most small molecule drug discovery project teams at Genentech.

Keywords: Drug discovery, high throughput analysis, lipophilicity, Log D, physicochemical property, UPLC-MS/MS.


Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy