Foster S J, Sovak M
Biophysica Foundation, La Jolla, CA 92037.
Invest Radiol. 1988 Sep;23 Suppl 1:S106-9. doi: 10.1097/00004424-198809001-00011.
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.
具有药理作用的造影剂（CM）必须具有高度水溶性，以形成稳定的过饱和溶液。碘海醇和碘克沙醇都含有潜在的异构中心，这些异构中心源于D，L-羟烷基、氨基甲酰基取代基、烷基化苯胺氮和乙酰化苯胺。D，L-异构体是单独的化合物，都具有高度水溶性且同样具有高度亲水性。氨基甲酰基旋转异构体是由相邻碘原子的空间位阻导致的，在生理温度范围内可相互转化；只有在低温下，高场核磁共振（NMR）才能识别它们。烷基化苯胺产生的异构体是固定的，但由于它们只能参照固定的氨基甲酰基存在，因此在生理温度下不相关。N-乙酰基内/外异构体可从醇类溶剂中结晶出来，并可通过高压液相色谱（HPLC）以及氢-1（1H）和碳-13（13C）核磁共振进行识别。它们在水中迅速相互转化，形成稳定且高度可溶的混合物。基于HPLC分析，碘海醇或碘克沙醇的所有异构体同样具有高度亲水性，预计与生物大分子的结合力较低，同时具有较高的生物耐受性。由于这些混合物不可避免，因此必须将它们视为一种药理实体。
