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

Summary Background: During the production process of the X-ray contrast agent iodixanol the drug substance may be exposed to acid, base, air, heat and daylight, conditions that may cause decomposition products. Objective: To investigate the chemical stability of iodixanol under accelerating 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 ultraviolet irradiation via a Norrish Type-II reaction. Basic conditions (pH 14) combined with heat (60 °C) initiated a cyclization reaction. Less than 1% iodixanol decomposed in solution heated to 140 °C for 2 days or under both basic conditions (pH 11, 20 °C, 5 days) and acidic conditions (pH 0·4, 80 °C, 5 days) or under oxygen atmosphere (100 °C, 3 days). Conclusion: Even under highly acidic and basic conditions, iodixanol is stable.