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7678836 
Journal Article 
Determination of the D- and L-enantiomers of modafinil in human plasma utilizing liquid-liquid extraction and high-performance liquid chromatography 
Gorman, SH 
1999 
Yes 
Journal of Chromatography B: Biomedical Sciences and Applications
ISSN: 1387-2273
EISSN: 1878-5603 
730 
1 
1-7 
English 
10437666 
WOS:000081349700001 
Modafinil, DL-2-[(diphenylmethyl)sulfinyl]acetamide (Provigil), which is chiral at its sulfur atom, is a novel wake-promoting agent currently being developed as the racemate in the United States by Cephalon, Inc. In order to characterize the pharmacokinetic properties of each enantiomer, a stereospecific high-performance liquid chromatography (HPLC) method has been developed for simultaneous determination of D- and L-modafinil in human plasma. The analytes are extracted from plasma into a mixture of hexane-methylene chloride-triethylamine (55:45:2, v/v/v) and then resolved on an EM Separations ChiraDex beta-cyclodextrin column at 12 degrees C using an isocratic mobile phase of 0.020 M, pH 3.0 phosphate buffer-acetonitrile (84:14, v/v). D- and L-modafinil, and the internal standard, 3,3-diphenylpropylamine, are monitored by UV detection at 225 nm. The two major circulating metabolites, modafinil acid and modafinil sulfone, have been shown not to interfere with the assay. Using 0.200 ml of plasma for extraction, the quantifiable range of the assay is 0.100 to 15.0 microg/ml for each enantiomer. The utility of the assay for the characterization of D- and L-modafinil pharmacokinetics in humans after single and multiple oral doses of racemic modafinil has been demonstrated. 
enantiomer separation; modafinil