Isolation of an endogenous ligand solute from uremic serum was performed by high-performance liquid chromatography. This ligand solute inhibited the binding of diphenylhydantoin and tryptophan to plasma protein, and was considered to be one of the endogenous drug-binding inhibitors present in uremic serum. The gas chromatographic-mass spectrometric analysis revealed that this inhibitor is 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid, which is known to be a constituent of urine.
The profiling of endogenous ligand solutes in sera of patients with uremia was performed by using an ultrafiltration device and high-performance liquid chromatography. Seventeen endogenous ligand solutes, which are ultraviolet-absorbing substances, were detected in a sample volume of 40 μl, and four ligand solutes were tentatively identified as indoxylsulfate, hippuric acid, 2-hydroxybenzoylglycine, and 3-indoleacetic acid. One of these ligand solutes designated as peak P was thought to be a candidate for a major drug-binding inhibitor in uremia.
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