KINETIC-ANALYSIS OF MOLECULAR INTERCONVERSION OF IMMUNOSUPPRESSANT FK506 BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

High-performance liquid chromatography of FK506, a macrolide immunosup pressant, 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 interco nversion at high temperature. When the column was cooled to 0-degrees- C, two sharp peaks were observed because essentially no interconversio n occurred at 0-degrees-C during elution. Analysis of the chromatogram s obtained at various eluant flow rates indicated that the conversion of the two forms follows first-order kinetics, and the apparent activa tion energies for the conversions were calculated. The interconvertibi lity between two molecular forms may be related to the immunosuppressi ve activity.