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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.

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Lhöest, G J Verbeeck, R K Maton, Nicole [UCL] Latinne, Dominique [UCL] Laurent, André [UCL]

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.

Document type Article de périodique (Journal article) – Journal Article
Publication date 1994
Journal information "Clinical chemistry" - Vol. 40, no. 5, p. 740-4 (1994)
Peer reviewed yes
issn 0009-9147
Publication status Publié
Affiliation UCL - MD/MIGE - Département de microbiologie, d'immunologie et de génétique
MESH Subject Chromatography, High Pressure Liquid ; Humans ; Immunosuppression ; Lymphocyte Culture Test, Mixed ; Magnetic Resonance Spectroscopy ; Methylation ; Microsomes, Liver - chemistry ; Spectrometry, Mass, Fast Atom Bombardment ; Tacrolimus - analogs & derivatives - analysis - metabolism - pharmacology
Links
Bibliographic reference Lhöest, G J ; Verbeeck, R K ; Maton, Nicole ; Latinne, Dominique ; Laurent, André. 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.. In: Clinical chemistry, Vol. 40, no. 5, p. 740-4 (1994)
Permanent URL http://hdl.handle.net/2078.1/29609