Enantiomeric Determination of the Phenylmorpholinol Metabolite of Bupropion in Human Plasma Using Coupled Achiral–Chiral Liquid Chromatography

✍ Scribed by Raymond F. Suckow; Ming F. Zhang; Thomas B. Cooper

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 142 KB
• Volume: 11
• Category: Article
• ISSN: 0269-3879
• DOI: 10.1002/(sici)1099-0801(199705)11:3<174::aid-bmc681>3.0.co;2-e

✦ Synopsis

A coupled achiral-chiral stationary phase liquid chromatographic technique was developed to separate and quantitate the enantiomers of the phenylmorpholinol 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 stationary phase which resolved 2 into the ( + ) and ( Ϫ ) stereoisomers using an aqueous mobile phase of potassium phosphate (pH = 6.25) and 5% 2-propanol. All eluting compounds were monitored using UV detection at 214 nm, and no plasma endogenous material or other commonly used psychotropic drugs were found to interfere. Within-day and between-day variations were 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 ( Ϫ ) enantiomer to the extent of about 96% of total 2. The potential clinical implications of these results are not known since all previous pharmacological studies were carried out with the racemic 2.