Determination of the geometrical diarylpropenamine isomers in feces by high-performance liquid chromatography

Diarylpropenamine derivatives are a class of compounds which have been eval uated as potential drug candidates. Here a specific and reproducible HPLC m ethod for the determination of cis- and trans-isomers of the unsubstituted derivative, 3-(4'-bromo-[1,1'-biphenyl]-4-yl)-3-(4-X-phenyl-N,N-dimethyl-2- propen-1-amine (I, where X=H) in feces is described. The analyte I and inte rnal standard, nitro derivative (II, where X=NO2), were isolated from the b asified biological matrix using a liquid-liquid extraction with ethyl aceta te followed by a solid-phase procedure performed on a silica cartridge. The organic phase was evaporated to dryness, the residue was reconstituted in mobile phase and injected into the HPLC system. The analytes were eluted wi th ethyl acetate-hexane-triethylamine (59:40:1) in HPLC column (silica) and detected by UV spectrophotometry at 272 nm. Linearity, precision and accur acy data for feces standards after extraction were acceptable. The method h as been applied to analyses of feces samples from rats dosed with I, in whi ch it could be anticipated that fecal excretion is quantitatively the major route for I elimination. (C) 1999 Elsevier Science B.V. All rights reserve d.