Wallemacq P E, Lhoëst G, Dumont P
Department of Pharmacology, Catholic University of Louvain, Brussels, Belgium.
Biomed Environ Mass Spectrom. 1989 Jan;18(1):48-56. doi: 10.1002/bms.1200180107.
Metabolism of cyclosporin A (CsA) was studied in a model of isolated and perfused rabbit liver, and in man. After diethyl ether extraction, CsA metabolites were separated and successfully purified by a combination of two high-performance liquid chromatographic (HPLC) procedures. A normal-phase HPLC methodology was used to separate most of the metabolites, and further separation and purification were optimized with a reversed-phase HPLC method. 27 different CsA metabolites were separated, collected, and characterized by fast atom bombardment mass spectrometry. In addition to several metabolites already described (OL-1, OL-17, OL-18 and OL-21), new compounds (of original molecular weights 1236, 1222 and 1174, and numerous structural isomers of previously reported molecular weights) were isolated from rabbit and human bile. Mass spectral analysis of two of these new metabolites strongly suggests vicinal dihydrodiol (mol. wt 1236) and N-demethylated vicinal dihydrodiol (mol. wt 1222) structures. These two new metabolites most probably derive from an epoxide as a preliminary intermediate.
在离体灌注兔肝模型及人体中研究了环孢素A（CsA）的代谢情况。经乙醚萃取后，通过两种高效液相色谱（HPLC）方法相结合，对CsA代谢产物进行分离并成功纯化。采用正相HPLC方法分离大多数代谢产物，并用反相HPLC方法进一步优化分离和纯化。分离出27种不同的CsA代谢产物，通过快速原子轰击质谱对其进行收集和表征。除了几种已描述的代谢产物（OL-1、OL-17、OL-18和OL-21）外，还从兔和人胆汁中分离出了新化合物（原始分子量分别为1236、1222和1174，以及先前报道分子量的众多结构异构体）。对其中两种新代谢产物的质谱分析强烈表明存在邻位二氢二醇（分子量1236）和N-去甲基邻位二氢二醇（分子量1222）结构。这两种新代谢产物很可能源自环氧化物作为初步中间体。
