Stability of the X-ray contrast agent iodixanol=3,3',5,5'-tetrakis(2,3-dihydroxypropylcarbamoyl)-2,2',4,4',6,6'-hexaiodo-N,N'-(2-hydroxypropane-1,3-diyl)-diacetanilide towards acid, base, oxygen, heat and light

Background: During the production process of the X-ray contrast agent iodix anol the drug substance may be exposed to acid, base, air, heat and dayligh t, conditions that may cause decomposition products. Objective: To investigate the chemical stability of iodixanol under acceler ating conditions. Method: Chemometrical stability studies were undertaken to investigate the effect of acid and base on the contrast agent's stability. Results: Cleavage of the central bridge in iodixanol occurred under ultravi olet irradiation via a Norrish Type-II reaction. Basic conditions (pH 14) c ombined with heat (60 degrees C) initiated a cyclization reaction. Less tha n 1% iodixanol decomposed in solution heated to 140 degrees C for 2 days or under both basic conditions (pH 11, 20 degrees C, 5 days) and acidic condi tions (pH 0.4, 80 degrees C, 5 days) or under oxygen atmosphere (100 degree s C, 3 days). Conclusion: Even under highly acidic and basic conditions, iodixanol is sta ble.