Isolation and structural identification of 9hydroxy-9desmethyl-cyclosporine.
A metabolite of cyclosporine has been isolated and its structure identified through use of HPLC and tandem mass spectroscopy. Fast atom bombardment mass spectrometry of an HPLC fraction co-eluting with 1 eta hydroxy-cyclosporine (M17) indicated that the mass of this metabolite was 2 Da greater than that of cyclosporine. Further isolation by HPLC yielded a pure fraction, which we analyzed with tandem mass spectrometry. Linear acyl fragment ions originating from the metabolite under collision-induced dissociation were consistent with the difference in mass being associated with amino acid 9 in the cyclosporine backbone. We propose a nomenclature system for future discussion of cyclosporine metabolites.
Bowers
L D
LD
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis 55455.
Norman
D D
DD
Yan
X X
XX
Scheeler
D
D
Carlson
K L
KL
D000595:Amino Acid Sequence; D002851:Chromatography, High Pressure Liquid; D003524:Cyclosporins / Q000302:isolation & purification* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009626:Terminology as Topic
D003524:Cyclosporins; C066474:9-hydroxy-9-desmethylcyclosporine