COMPETITIVE PARTICLE CONCENTRATION FLUORESCENCE IMMUNOASSAYS FOR MEASURING ANTIDIABETIC DRUG LEVELS IN MOUSE PLASMA

Two competitive particle concentration fluorescence immunoassays were developed to measure blood levels of analogs of anti-diabetic drugs be ing tested in diabetic mice. Ligands that contained the active pharmac ophores were conjugated to PPD for immunization and to beta-phycoeryth rin for use as a tracer in the immunoassays. Approximately 90% of 262 compounds assayed were detectable at less than 120 nM in plasma which was well below the estimated therapeutic level of 1 mu M for lowering blood glucose. These data were used to define the bioavailability of t est compounds and assist in decisions of constructing active analogs. Of additional interest, we noted crossreactivity of one monoclonal ant ibody for 3 different compound classes that are all known to bind with varying affinities to peroxisome proliferator-activated receptors. (C ) 1997 Elsevier Science B.V.