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- Title
Fast log P determination by ultra-high-pressure liquid chromatography coupled with UV and mass spectrometry detections.
- Authors
Henchoz, Yveline; Guillarme, Davy; Martel, Sophie; Rudaz, Serge; Veuthey, Jean-Luc; Carrupt, Pierre-Alain
- Abstract
Ultra-high-pressure liquid chromatography (UHPLC) systems able to work with columns packed with sub-2 μm particles offer very fast methods to determine the lipophilicity of new chemical entities. The careful development of the most suitable experimental conditions presented here will help medicinal chemists for high-throughput screening (HTS) log Poct measurements. The approach was optimized using a well-balanced set of 38 model compounds and a series of 28 basic compounds such as β-blockers, local anesthetics, piperazines, clonidine, and derivatives. Different organic modifiers and hybrid stationary phases packed with 1.7-μm particles were evaluated in isocratic as well as gradient modes, and the advantages and limitations of tested conditions pointed out. The UHPLC approach offered a significant enhancement over the classical HPLC methods, by a factor 50 in the lipophilicity determination throughput. The hyphenation of UHPLC with MS detection allowed a further increase in the throughput. Data and results reported herein prove that the UHPLC-MS method can represent a progress in the HTS-measurement of lipophilicity due to its speed (at least a factor of 500 with respect to HPLC approaches) and to an extended field of application. [Figure not available: see fulltext.]
- Subjects
LIQUID chromatography; DRUG development; DRUG lipophilicity; PHARMACOKINETICS; EXTRAPOLATION
- Publication
Analytical & Bioanalytical Chemistry, 2009, Vol 394, Issue 7, p1919
- ISSN
1618-2642
- Publication type
Article
- DOI
10.1007/s00216-009-2862-1