Clinical Chemistry
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Clinical Chemistry 40: 740-744, 1994;
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Clinical Chemistry, Vol 40, 740-744, Copyright © 1994 by American Association for Clinical Chemistry

15-Desmethyl FK-506 and 15,31-desmethyl FK-506 from human liver microsomes: isolation, identification (by fast atom bombardment mass spectrometry and NMR), and evaluation of in vitro immunosuppressive activity

GJ Lhoest, N Maton, D Latinne, A Laurent and RK Verbeeck
Department of Pharmaceutical Sciences, UCL, FATC, Brussels, Belgium.

15-Desmethyl FK-506 and 15,31-desmethyl FK-506 metabolites extracted from incubated human liver microsomes were separated by normal and reversed-phase HPLC. The metabolites were identified by fast atom bombardment/mass spectrometry and nuclear magnetic resonance spectroscopy. The in vitro 50% inhibitory concentration, tested against bidirectional mixed lymphocyte reactions, was 325 mg/L for 15,31- desmethyl FK-506 and 4 mg/L for 15-desmethyl FK-506, indicating that these products of FK-506 demethylation retain in vitro immunosuppressive activity.


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Copyright © 1994 by the American Association for Clinical Chemistry.