The contribution of the hydrogen bond acidity on the lipophilicity of drugs estimated from chromatographic measurements.

The influence of the hydrogen bond acidity when the 1-octanol/water partition coefficient (log P(o/w)) of drugs is determined from chromatographic measurements was studied in this work. This influence was firstly evaluated by means of the comparison between the Abraham solvation parameter model when it is applied to express the 1-octanol/water partitioning and the chromatographic retention, expressed as the solute polarity p. Then, several hydrogen bond acidity descriptors were compared in order to determine properly the log P(o/w) of drugs.

Evaluation of fluorescence anisotropy to assess drug-lipid membrane partitioning.

Purpose: We evaluated fluorescence anisotropy measurements as an alternative technique to estimate drug-lipid membrane partitioning of fluorescent solutes.

Methods: The lipid bilayer partitioning of six drugs (logP in octanol/water between 2.6 and 5.

Extension of the liquid chromatography/quantitative structure-property relationship method to assess the lipophilicity of neutral, acidic, basic and amphotheric drugs.

A reported chromatographic method to determine the 1-octanol/water partition coefficient (logP(o/w)) has been used to estimate the lipophilicity of 33 drugs with diverse structures and functionalities, including neutral, acid, basic, and amphoteric compounds. The applicability of the chromatographic method has been extended to the UHPLC technique, and the results obtained were compared to those obtained from conventional HPLC. No significant difference between the results obtained by both techniques is noticed.

Lipophilicity assessment of basic drugs (log P(o/w) determination) by a chromatographic method.

A previously reported chromatographic method to determine the 1-octanol/water partition coefficient (log P(o/w)) of organic compounds is used to estimate the hydrophobicity of bases, mainly commercial drugs with diverse chemical nature and pK(a) values higher than 9. For that reason, mobile phases buffered at high pH to avoid the ionization of the solutes and three different columns (Phenomenex Gemini NX, Waters XTerra RP-18 and Waters XTerra MS C(18)) with appropriate alkaline-resistant stationary phases have been used. Non-ionizable substances studied in previous works were also included in the set of compounds to evaluate the consistency of the method.

Determination of the hydrophobicity of organic compounds measured as logP(o/w) through a new chromatographic method.

A new chromatographic method to determine the octanol-water partition coefficient (logP(o/w)) of organic substances is proposed in this paper. This method is based on a previously reported model that relates the retention factor in reversed-phase liquid chromatography with solute (p), mobile phase (P(m)(N)) and stationary phase (P(s)(N)) polarity parameters: logk=(logk)(0)+p(P(m)(N)-P(s)(N)). P(m)(N) values are calculated through expressions that depend only on the organic solvent fraction in the mobile phase.