Analysis of basic compounds on a silica column with an aqueous methanol eluent. The use of quantitative structure-retention relationships in metabolite identification.

High-performance liquid chromatography data for 69 mono-functional aryl-alkyl amines was generated using a silica column and an aqueous methanol eluent (pH 9.1). Retention was shown to be due to a cation-exchange mechanism and was controlled by the solute pKa and the degree and type of substitution at or near the basic centre. The effect of various substituents--some common to metabolic transformation--could be quantified using the group contribution values (tau). The study was extended to include a further 32 compounds representative of five diverse drug classes. The group contribution data for these drugs and metabolites were similar to those for the model compounds. A number of common biotransformations were well characterised, including N-desmethylation, N,N-didesmethylation and ring hydroxylation. The data demonstrates how the group contribution values can be used to help elucidate the identity of a metabolite from chromatographic data.