Lipophilicity measurement of drugs by reversed phase HPLC over Wide pH range using an alkaline-resistant silica-based stationary phase, XBridge Shield RP(18).
We propose a reversed phase HPLC (RP-HPLC) with an alkaline-resistant silica-based stationary phase, XBridge Shield RP(18), for the determination of the lipophilicity of drugs with diverse chemical nature ranging from acidic to basic. A set of 40 model compounds with well-defined solvatochromic parameters was selected to allow a broad distribution of structural properties. The chromatographic results showed that the lipophilicity index log k(w) obtained with XBridge Shield RP(18) was well correlated with experimental log P(oct) values (r(2)=0.96). Linear solvation free-energy relationship (LSER) analyses revealed that the retention mechanism of the stationary phase and 1-octanol/water partitioning were controlled by almost the same balance of intermolecular forces (hydrophobicity as expressed by the van der Waals volume V(w), H-bond acceptor basicity beta, and dipolarity/polarizability pi*). The results showed that XBridge Shield RP(18) phase overcomes the shortcomings of the silica-based stationary phases, the application of which to lipophilicity measurements had been limited to neutral and acidic compounds.
Liu
Xiangli
X
Department of Pharmaceutical Technology, Friedrich-Schiller-Universität Jena, Jena, Germany. Xiangli.Liu@uni-jena.de
Hefesha
Hossam
H
Tanaka
Hideji
H
Scriba
Gerhard
G
Fahr
Alfred
A
D020003:1-Octanol / Q000737:chemistry; D000465:Algorithms; D000468:Alkalies; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D008055:Lipids / Q000737:chemistry*; D017646:Organosilicon Compounds / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D012822:Silicon Dioxide / Q000737:chemistry*; D012997:Solvents; D013056:Spectrophotometry, Ultraviolet; D014867:Water / Q000737:chemistry
D000468:Alkalies; D008055:Lipids; D017646:Organosilicon Compounds; D004364:Pharmaceutical Preparations; D012997:Solvents; D014867:Water; D012822:Silicon Dioxide; D020003:1-Octanol