Kinetic analysis of molecular interconversion of immunosuppressant FK506 by high-performance liquid chromatography.
High-performance liquid chromatography of FK506, a macrolide immunosuppressant, was performed on a reversed-phase column. The peak was broad with the column kept at room temperature, which was accounted for by slow interconversion between the two forms of FK506. With the use of a heated column, a sharp peak was observed because of the rapid interconversion at high temperature. When the column was cooled to 0 degree C, two sharp peaks were observed because essentially no interconversion occurred at 0 degree C during elution. Analysis of the chromatograms obtained at various eluant flow rates indicated that the conversion of the two forms follows first-order kinetics, and the apparent activation energies for the conversions were calculated. The interconvertibility between the two molecular forms may be related to the immunosuppressive activity.
Nishikawa
T
T
Department of Clinical Pathology, Kitasato University School of Medicine, Kanagawa, Japan.
Hasumi
H
H
Suzuki
S
S
Kubo
H
H
Ohtani
H
H
D002851:Chromatography, High Pressure Liquid; D007166:Immunosuppressive Agents / Q000737:chemistry*; D007536:Isomerism; D007700:Kinetics; D008968:Molecular Conformation; D013056:Spectrophotometry, Ultraviolet; D016559:Tacrolimus / Q000737:chemistry*; D013696:Temperature
D007166:Immunosuppressive Agents; D016559:Tacrolimus