DEACTIVATED HYDROCARBONACEOUS SILICA AND IMMOBILIZED ARTIFICIAL MEMBRANE STATIONARY PHASES IN HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF HYDROPHOBICITIES OF ORGANIC-BASES - RELATIONSHIP TO LOG-P AND CLOGP

Retention parameters for a series of 29 organic base drugs (including 17 phenothiazine derivatives) were measured by reversed-phase high-per formance liquid chromatography (HPLC) employing new columns of distinc tive partition properties. One column was a deactivated alkyl-bonded s ilica and two others were packed with lecithin bonded propylamino-sili ca, i.e. the immobilized artificial membrane (IAM) columns; one of the IAM stationary phases had the unreacted propylamine moieties addition ally end-capped with methylglycolate. The highly deactivated hydrocarb onaceous silica column showed regular rectilinear relationships betwee n logarithms of chromatographic capacity factors and the content of or ganic modifier in aqueous eluent; it is suitable for generating a chro matographic scale of hydrophobicity. Such a scale (hydrocarbonaceous) is different from that provided by measurement of partitioning of solu tes between n-octanol and water (alkanol log P scale). The relative hy drophobicity parameters determined by HPLC on the IAM columns were dif ferent from both log P scale and from the hydrocarbonaceous chromatogr aphic hydrophobicity scale. The hydrophobicity parameter, CLOGP, theor etically calculated by the fragmental methods, correlated better than log P with chromatographic hydrophobicity parameters. It has been post ulated that each hydrophobicity measuring system reveals some specific aspects of the hydrophobicity phenomenon and that the nature of hydro phobic binding sites on receptors and plasma proteins may require diff erent hydrophobicity models than drug permeation through biological me mbranes. By means of HPLC, diverse hydrophobicity measures can readily be determined, among which those most suitable for specific QSAR appl ications can be identified.