A sulfate conjugate of cyclosporin.
A metabolite of cyclosporin A was isolated from human bile and plasma. The material was identified as a sulfate conjugate by plasma desorption time-of-flight mass spectrometry and by in vitro technique using human liver preparations and radiolabeled substrates. A sulfate ester at the beta-carbon on the amino acid no. 1, the methylbutenyl-threonine amino acid, of cyclosporin was synthesized as a reference, and found to have the same plasma desorption time-of-flight and direct chemical ionization mass spectrum as the isolated metabolite. It also had the same chromatographic properties on both an ion-pair reversed phase system and an ion-exchanger. Hydrolysis with sulfuric acid on the purified and synthetic metabolite gave free cyclosporin. The amino acids in the metabolite, analyzed by gas chromatography/mass spectrometry, were the same as those in cyclosporin. Free cyclosporin was not found upon hydrolysis with commercial sulfatases.
Henricsson
S
S
Department of Clinical Pharmacology, Karolinska Institute, Huddinge Hospital, Sweden.
D001646:Bile / Q000378:metabolism; D002849:Chromatography, Gas; D003524:Cyclosporins / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism; D013058:Mass Spectrometry; D013431:Sulfates / Q000378:metabolism*
D003524:Cyclosporins; D013431:Sulfates