Novel RPLC stationary phases for lipophilicity measurement: solvatochromic analysis of retention mechanisms for neutral and basic compounds.
An RPLC was developed to rapidly determine lipophilicity of neutral and basic compounds using three base deactivated RPLC stationary phases particularly designed for the analysis of basic compounds, namely, Supelcosil ABZ(+)Plus, Discovery RP Amide C16, and Zorbax Extend C18. The work consisted of three sets of experiments. In the first log kw values of neutral compounds were extrapolated using hydroorganic mobile phases at different compositions. Good correlation between log kw and log Poct indicated that the method was appropriate for these supports, without adding a silanol masking agent. In the second set of experiments, isocratic log k values of neutral and basic compounds were measured with three different mobile phases. The best estimation of lipophilicity was obtained for neutral and basic compounds when the secondary interactions were strongly reduced (i. e., when basic compounds were under their neutral form). In the third set of experiments, isocratic retention factors of basic compounds (in their neutral form) were measured with a high-pH mobile phase, on a chemically stable support (Zorbax Extend C18). Under these chromatographic conditions, correlation between the isocratic retention factors and log Poct (log D10.5) for basic compounds was similar to that for neutral compounds.
Stella
Cinzia
C
Laboratory of Pharmaceutical Analytical Chemistry, School of Pharmaceutical Sciences, EPGL, University of Geneva, Switzerland. Cinzia.Stella@pharm.unige.ch
Galland
Alexandra
A
Liu
Xiangli
X
Testa
Bernard
B
Rudaz
Serge
S
Veuthey
Jean-Luc
JL
Carrupt
Pierre-Alain
PA
D002853:Chromatography, Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013329:Structure-Activity Relationship
D008055:Lipids; D012997:Solvents