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)-diacetanili de towards acid, base, oxygen, heat and light.
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.


METHODS
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 degrees C) initiated a cyclization reaction. Less than 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 conditions (pH 0.4, 80 degrees C, 5 days) or under oxygen atmosphere (100 degrees C, 3 days).


CONCLUSIONS
Even under highly acidic and basic conditions, iodixanol is stable.
Priebe
H
H
NYCOMED Imaging R & D, Oslo, Norway. HP@nycomed.com
Aukrust
A
A
Bjørsvik
H R
HR
Tønseth
C P
CP
Wiggen
U N
UN
D003287:Contrast Media / Q000737:chemistry* / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008027:Light; D010100:Oxygen; D014283:Triiodobenzoic Acids / Q000737:chemistry* / Q000378:metabolism; D014466:Ultraviolet Rays
D003287:Contrast Media; D014283:Triiodobenzoic Acids; C044834:iodixanol; D010100:Oxygen