STEREOSPECIFIC AND SIMULTANEOUS HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC ASSAY OF FLOSEQUINAN AND ITS METABOLITES IN HUMAN PLASMA

A high-performance liquid chromatographic method was developed for the simultaneous determination of the enantiomers of flosequinan [(+/-)-7-fluoro-1-methyl-3-methylsulphinyl-4-quinolone] and its metabolites, flosequinan sulphide and sulphone, in human plasma. These compounds were extracted from plasma with chloroform. The compounds were separated on a chiral stationary phase of cellulose tris-3,5-dimethylphenylcarbamate coated on silica gel, with a mobile phase of ethanol-methanol (22:78, v/v). Flosequinan enantiomers and flosequinan sulphone were determined by UV detection at a wavelength of 320 nm. Flosequinan sulphide was determined using fluorescence detection (excitation at 370 nm, emission at 430 nm). Standard curves were linear over the concentration range 5-10000 ng/ml for both enantiomers and flosequinan sulphide, and 20-10000 ng/ml for flosequinan sulphone. This method is adequate for pharmacokinetic studies of the enantiomers of flosequinan and its metabolites.