A novel tool for structure assignment of hydroxylated metabolites of (arylpiperazinylbutyl) oxindole derivatives based on relative HPLC retention times

Publication date: Available online 11 March 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Éva Szabó, Györgyi Koványi-Lax, Gábor Szénási, András Dancsó, Loránd Kiss, Róbert Kormány, Gyula Simig, Gábor Németh, Balázs VolkAbstractIncubation of oxindole derivatives containing an arylpiperazine pharmacophore in rat liver microsomes in vitro formed several metabolites hydroxylated at various positions of the aromatic rings of the oxindole carbocycle or the arylpiperazine moiety. In order to substitute the sites of metabolic attack on these positional isomers the exact structure of the molecules had to be identified. As polarities of the compounds depend on the site of hydroxylation we measured retention times of the metabolites using reversed-phase HPLC. It was noted that the relative retention times (RRT, the ratio of the retention time of the metabolite and the parent compound) fell into distinct narrow ranges for metabolites identified by MS spectra as positional isomers. These RRT ranges correlated with the positions of hydroxylation. The hypothesis was validated by synthesis of hydroxy compounds of known structure and by determination of their RRT values. Change in the chromatographic parameters such as column type, eluent, gradient time and temperature did not impede the identification of the sites of hydroxylation as the RRT pattern remained similar to the original one. The new empirical method proposed in our study can be used for te...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research