Lipophilicity determination of highly lipophilic compounds by liquid chromatography.
Different experimental strategies using short columns in both conventional liquid chromatography (HPLC) and ultra-high pressure liquid chromatography (UHPLC) were evaluated to allow, for the first time with these techniques, the lipophilicity determination of compounds with log P>5. Various organic modifiers, stationary phases, and elution modes were tested on 14 rigid compounds with a CLogP between 5 and 8, and 38 compounds with log P(oct) from 0 to 5. The best results in HPLC were obtained with the 20-mm Discovery RP Amide C16 stationary phase in isocratic mode using MeOH as organic modifier. To improve analysis time, the UHPLC approach was then evaluated. Consequently, a generic method was developed with a 30-mm Acquity BEH Shield RP18 column in gradient mode using MeOH as organic modifier, allowing a fourfold gain of time compared to the HPLC method, for the highly lipophilic compounds tested. Finally, the most rapid and accurate results were obtained with a 10-mm Hypersil GOLD Javelin HTS stationary phase in UHPLC, enabling an eightfold gain of time compared to the HPLC method.
Guillot
Amandine
A
School of Pharmaceutical Sciences, University of Geneva, Quai Ernest Ansermet 30, CH-1211, Geneva 4.
Henchoz
Yveline
Y
Moccand
Cyril
C
Guillarme
Davy
D
Veuthey
Jean-Luc
JL
Carrupt
Pierre-Alain
PA
Martel
Sophie
S
D000465:Algorithms; D002021:Buffers; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D008055:Lipids / Q000737:chemistry*; D000432:Methanol / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D010599:Pharmacokinetics; D012995:Solubility; D012997:Solvents
D002021:Buffers; D007202:Indicators and Reagents; D008055:Lipids; D004364:Pharmaceutical Preparations; D012997:Solvents; D000432:Methanol