DETERMINATION OF THE TOTAL CONCENTRATION OF HIGHLY PROTEIN-BOUND DRUGS IN PLASMA BY ONLINE DIALYSIS AND COLUMN LIQUID-CHROMATOGRAPHY - APPLICATION TO NONSTEROIDAL ANTIINFLAMMATORY DRUGS

The potential of on-line dialysis as a sample preparation procedure fo r compounds highly bound to plasma proteins is evaluated, using non-st eroidal anti-inflammatory drugs as model compounds and column liquid c hromatography as the separation technique. Different strategies to red uce the degree of drug-protein binding and so increase the analyte rec overy are systematically explored and discussed: alteration of the con formation of the binding protein by changing the pH of the sample or b y adding an organic solvent, addition of several displacing compounds and combinations of such approaches. A fully automated method is prese nted for the determination of ketoprofen, ibuprofen, flurbiprofen, fen oprofen and naproxen in human plasma, in which the absolute analyte re coveries are increased from 0-1% (untreated samples) to 40-65%. Releva nt analytical data are given to demonstrate the reliability of the pro posed procedure.