Isomerism in iohexol and ioxilan. Analysis and implications.
Pharmacologically useful contrast media (CM) must be highly water-soluble to form stable supersaturated solutions. Iohexol and ioxilan both contain centers of potential isomerism stemming from the D,L hydroxyalkyls, the carbamoyl substituents, the alkylated anilide nitrogen and the acetylated anilide. The D,L isomers are individual compounds, both highly water-soluble and equally highly hydrophilic. The carbamoyl rotamers result from steric restriction by the adjacent iodines, and are interconvertible at physiologic temperature ranges; only at low temperatures can high field nuclear magnetic resonance (NMR) identify them. The isomers resulting from the alkylated anilide are fixed, but since they can exist only by reference to fixed carbamoyls, they are not relevant at physiologic temperatures. The N-acetyl endo-/exo-isomers are crystallizable from alcoholic solvents and identifiable by high-pressure liquid chromatography (HPLC) and hydrogen-1 (1H) and 13C NMR. They interconvert rapidly in water, forming stable and highly soluble mixtures. All isomers of iohexol or ioxilan, based on HPLC, are similarly highly hydrophilic, and are expected to show low binding to biomacromolecules with a concomitantly high biological tolerance. Since these mixtures are unavoidable, they must be considered a pharmacologic entity.
Foster
S J
SJ
Biophysica Foundation, La Jolla, CA 92037.
Sovak
M
M
D002851:Chromatography, High Pressure Liquid; D003287:Contrast Media; D007472:Iohexol / Q000031:analogs & derivatives*; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D013329:Structure-Activity Relationship
D003287:Contrast Media; D007472:Iohexol; C055357:ioxilan