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.

Abstract

Retention parameters for a series of 29 organic base drugs (including 17 phenothiazine derivatives) were measured by reversed-phase high-performance liquid chromatography (HPLC) employing new columns of distinctive partition properties. One column was a deactivated alkyl-bonded silica and two others were packed with lecithin-bonded propylamino-silica, i.e. the immobilized artificial membrane (IAM) columns; one of the IAM stationary phases had the unreacted propylamine moieties additionally end-capped with methylglycolate. The highly deactivated hydrocarbonaceous silica column showed regular rectilinear relationships between logarithms of chromatographic capacity factors and the content of organic modifier in aqueous eluent; it is suitable for generating a chromatographic scale of hydrophobicity. Such a scale (hydrocarbonaceous) is different from that provided by measurement of partitioning of solutes between n-octanol and water (alkanol log P scale). The relative hydrophobicity parameters determined by HPLC on the IAM columns were different from both log P scale and from the hydrocarbonaceous chromatographic hydrophobicity scale. The hydrophobicity parameter, CLOGP, theoretically calculated by the fragmental methods, correlated better than log P with chromatographic hydrophobicity parameters. It has been postulated that each hydrophobicity measuring system reveals some specific aspects of the hydrophobicity phenomenon and that the nature of hydrophobic binding sites on receptors and plasma proteins may require different hydrophobicity models than drug permeation through biological membranes. By means of HPLC, diverse hydrophobicity measures can readily be determined, among which those most suitable for specific QSAR applications can be identified.