ENANTIOMERIC DETERMINATION OF THE PHENYLMORPHOLINOL METABOLITE OF BUPROPION IN HUMAN PLASMA USING COUPLED ACHIRAL-CHIRAL LIQUID-CHROMATOGRAPHY

A coupled achiral-chiral stationary phase liquid chromatographic techn ique was developed to separate and quantitate the enantiomers of the p henylmorpholinol metabolite (2) of the antidepressant bupropion (1) in human plasma. At the retention time of 2, a switching valve loaded a portion of the eluting compound onto a protein-bonded chiral stationar y phase which resolved 2 into the (+) and (-) stereoisomers using an a queous mobile phase of potassium phosphate (pH=6.25) and 5% 2-propanol . All eluting compounds were monitored using UV detection at 214 nm, a nd no plasma endogenous material or other commonly used psychotropic d rugs were found to interfere. Within-day and between-day variations we re less than 6% over the expected concentration range, and a limit of quantitation of about 125 ng/mL of 2 was observed. Steady-state plasma samples from 17 patients receiving 1 were found to contain the (-) en antiomer to the extent of about 96% of total 2. The potential clinical implications of these results are not known since all previous pharma cological studies were carried out with the racemic 2. (C) 1997 by Joh n Wiley & Sons, Ltd.