A method for determination of the plasma levels of modafinil enantiomers, (+/-)-modafinic acid and modafinil sulphone by direct human plasma injection and bidimensional achiral-chiral chromatography.

Coupled-column separation using restricted access media as the first dimension in order to exclude macromolecules and retain micromolecules has been successfully used for a number of biological fluids. This paper describes the first method developed and validated for the analysis in a single run of the enantiomers of modafinil and its two major metabolites. The method was developed using a bidimensional HPLC system by coupling a restricted access medium (RAM) bovine serum albumin (BSA) column (1.0 cm x 0.46 cm i.d.) to an amylose tris[(S)-1-phenylethylcarbamate] chiral column. The method was fully validated and showed good linearity, precision, accuracy, sensitivity and selectivity, allowing it to be used for pharmacokinetic studies. The quality of the performance of both columns was maintained with over 280 plasma injections of 100 microl.