Bioanalytical Methods for Iodixanol and Their Application to Studies on Metabolism and Protein Binding

The iodine-specific detection techniques X-ray fluorescence spectrometry, neutron activation analysis and radiochemical detections of (125)I-labelled substance are well suited for quantification of iodixanol in biological samples. The limit of detection is 60 microgram iodixanol/ml for X-ray fluorecence analysis and 1 to 10 microgram iodixanol/ml for neutron activation analysis. Reversed-phase high-performance liquid chromatography (HPLC) has been employed when selective determination of iodixanol was needed for identificational purposes or when quantification of very small amounts of iodixanol was essential. An optimized HPLC method for quantification of iodixanol in rat serum and urine is presented. The limit of detection for this method is 0.20 microgram iodixanol/ml for rat serum and 3.0 microgram iodixanol/ml for rat urine. When samples were analyzed by HPLC and thin layer chromatography, no metabolites of iodixanol were observed in rat, monkey or human urine, or in rat kidney and bile. Studies with equilibrium dialysis and HPLC determination of iodixanol showed no protein binding of the contrast agent in human plasma; the 95% confidence interval for the result was 0.0+/-2.1%.