Fast log P determination by ultra-high-pressure liquid chromatography coupled with UV and mass spectrometry detections.
Anal Bioanal Chem
; 394(7): 1919-30, 2009 Aug.
Article
en En
| MEDLINE
| ID: mdl-19533106
ABSTRACT
Ultra-high-pressure liquid chromatography (UHPLC) systems able to work with columns packed with sub-2 microm 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 P(oct) measurements. The approach was optimized using a well-balanced set of 38 model compounds and a series of 28 basic compounds such as beta-blockers, local anesthetics, piperazines, clonidine, and derivatives. Different organic modifiers and hybrid stationary phases packed with 1.7-microm 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Piperazinas
/
Clonidina
/
Antagonistas Adrenérgicos beta
/
Anestésicos
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
Anal Bioanal Chem
Año:
2009
Tipo del documento:
Article
País de afiliación:
Suiza