An enantioselective assay for (±)-modafinil

Enantiomers of modafinil, (diphenylmethyl)sulphinyl-2-acetamide, were separated by an amylose tris[(S)-1-phenylethylcarbamate] chiral stationary phase, using acetonitrile: water (25:75 v/v) as mobile phase, with excellent selectivity (alpha = 1.4) and resolution factors (R-s = 1.5). The assay involved a solid-phase extraction of the enantiomers of modafinil from plasma using a C-18 Cartridge. A good linear relationship was obtained in the concentration of 0.15-3 mug ml(-1) for each enantiomer. The method developed is sufficiently accurate and precise to be used for clinical samples and has a good selectivity with the two main circulating metabolites: the (diphenylmethyl)sulphinyl-2-acetic acid and (diphenylmethyl)sulphonyl-2-acetamide. The use of a polysaccharide-based column on multimodal elution was explored in developing the method. (C) 2001 Elsevier Science B.V. All rights reserved.