ISSN:
0887-6134
Keywords:
Chemistry
;
Analytical Chemistry and Spectroscopy
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
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 highperformance 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.
Additional Material:
7 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/bms.1200180107
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