A SULFATE CONJUGATE OF CYCLOSPORINE

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 β‐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. 1990 Nordic Pharmacological Society