Stability, blood partition, and protein binding of NQ12, a new naphthoquinone derivative

The stability of a new phospholipase A(2) inhibitor, NQ12, in various pH so lutions, human plasma, urine, and gastric juices, and rat liver homogenate, the blood partition of NQ12 between plasma and blood cells of rat blood, a nd the factors influencing the binding of NQ12 to 4% human serum albumin (H SA) using an equilibrium dialysis technique were evaluated. NQ12 was unstab le in various pH solutions, human plasma and urine, and rat liver homogenat e when incubated in a water-bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min. However, NQ12 was stable for up to 3-hr incubat ion in human gastric juice. The plasma-to-blood cell concentration ratios o f NQ12 were independent of NQ12 rat blood concentrations when the whole blo od was incubated for up to 2-hr; the mean (+/- standard deviation) values w ere 0.112 +/- 0.0650 and 0.172 +/- 0.105 at initial blood NQ12 concentratio ns of 10 and 20 mu g/ml, respectively. The binding of NQ12 to 4% HSA was co nsiderable (higher than 99%) at NQ12 concentrations ranging from 10 to 100 mu g/ml in 4% HSA. The unbound fraction of NQ12 was dependent on NQ12 conce ntrations, pHs of buffer, and HSA concentrations, but was independent of th e concentrations of sulfisoxazole or salicylic acid, incubation temperature , buffers containing various concentrations of chloride ion, and concentrat ions of heparin and alpha-1-acid glycoprotein.