Synthesis, analysis and toxicity of three compounds formed during the synthesis of iodixanol

The origin of 4-acetyl-2-[N-acetyl-3,5-bis(2,3-dihydroxypropylcarbamoyl)- 2,4,6-triiodoanilinomethyl]-5,7-diiodo-3,4-dihydro-2H-benzo[1,4]ox azine- 6,8-dicarboxylic acid bis(2,3-dihydroxypropylamide) = N-acetyl cyclized iodixanol, 2-[N-acetyl-3,5-bis-(2,3-dihydroxypropylcarbamoyl)-2,4,6- triiodoanilinomethyl]-5,7-diiodo-3,4-dihydro-2H-benzo[1,4]oxazine- 6,8-dicarboxylic acid bis(2,3-dihydroxypropylamide) = cyclized iodixanol and 5,5'-(N-acetyl-2-hydroxypropane-1,3-diyldiamino)bis[N,N'-bis(2,3- dihydroxypropyl)-2,4,6-triiodoisophthalamide] = deacetyl iodixanol in the manufacturing process of the X-ray contrast agent 3,3',5,5'-tetrakis(2,3-dihydroxypropylcarbamoyl)-2,2',4,4',6,6'-++ +hexaiodo- N,N'-(2-hydroxypropane-1,3-diyl)diacetanilide = iodixanol is discussed and their synthesis and purification are described. Their physical and toxicological properties, and analytical and spectroscopic data are summarized.