Abstract
A method has been developed which allows direct measurement of partition coefficients (log D, log P) using liquid chromatography-mass spectrometry (LC-MS). The high throughput, microtiter plate based protocol uses small quantities of 10 mM analyte in DMSO solution and is therefore amenable to standard archive and screening formats. Single Ion Monitoring (SIM) mass spectrometry is used to achieve optimal sensitivity. Experimental log D values for 34 known drugs have been determined, with partition coefficients ranging from -2 to 5, giving data very similar to literature values. In these analyses, deviations from known values average less than 0.3 log units. The sample handling and data processing have been significantly automated, and the protocol has been applied to over 800 in-house lead molecules to date. In its format, sensitivity, throughput, and amenability to automation, it represents significant progress in the direct measurement of partitioning behavior [1].
Keywords: high throughput log d determination, liquid chromatography mass spectrometry, single lon monitoring sim mass spectrometry, excretion adme, high throughput pharmaceutical profiling, cimetidine
Combinatorial Chemistry & High Throughput Screening
Title: High Throughput Log D Determination Using Liquid Chromatography-Mass Spectrometry
Volume: 4 Issue: 6
Author(s): Dean M. Wilson, Xiaoli Wang, Erin Walsh and Robyn A. Rourick
Affiliation:
Keywords: high throughput log d determination, liquid chromatography mass spectrometry, single lon monitoring sim mass spectrometry, excretion adme, high throughput pharmaceutical profiling, cimetidine
Abstract: A method has been developed which allows direct measurement of partition coefficients (log D, log P) using liquid chromatography-mass spectrometry (LC-MS). The high throughput, microtiter plate based protocol uses small quantities of 10 mM analyte in DMSO solution and is therefore amenable to standard archive and screening formats. Single Ion Monitoring (SIM) mass spectrometry is used to achieve optimal sensitivity. Experimental log D values for 34 known drugs have been determined, with partition coefficients ranging from -2 to 5, giving data very similar to literature values. In these analyses, deviations from known values average less than 0.3 log units. The sample handling and data processing have been significantly automated, and the protocol has been applied to over 800 in-house lead molecules to date. In its format, sensitivity, throughput, and amenability to automation, it represents significant progress in the direct measurement of partitioning behavior [1].
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Cite this article as:
Wilson M. Dean, Wang Xiaoli, Walsh Erin and Rourick A. Robyn, High Throughput Log D Determination Using Liquid Chromatography-Mass Spectrometry, Combinatorial Chemistry & High Throughput Screening 2001; 4 (6) . https://dx.doi.org/10.2174/1386207013330913
DOI https://dx.doi.org/10.2174/1386207013330913 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
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