title: In vitro immunosuppressive activity of tacrolimus dihydrodiol precursors obtained by chemical oxidation and identification of a new metabolite of SDZ-RAD by electrospray and electrospray-linked scan mass spectrometry.
abstract: Different tacrolimus epoxides and dihydrodiol epoxides arising from the chemical oxidation of the parent drug are described. Open-chain tautomeric forms involving the lactone function were identified for the tacrolimus epoxides. Moreover, the identification by electrospray and electrospray linked scan mass spectrometry of an SDZ-RAD C16-C27 O-demethyl 17, 18-19, 20-21, 22 tris-epoxide new metabolite isolated from pig liver microsomes is reported. The in vitro immunosuppressive activity, using mixed lymphocyte reactions of the two macrolide reported oxidation compounds are discussed.
authors.affiliation: Department of Pharmaceutical Sciences, UCL, Pharmacokinetics and Drug Metabolism Unit (PMNT), Laboratory of Mass Spectrometry, 7246 Av. E. Mounier, B-1200 Brussels, Belgium. lhoest@pmnt.ucl.ac.be
authors.forename: G
authors.initials: G
authors.lastname: Lhoëst
authors.forename: R
authors.initials: R
authors.lastname: Hertsens
authors.forename: R K
authors.initials: RK
authors.lastname: Verbeeck
authors.forename: N
authors.initials: N
authors.lastname: Maton
authors.forename: P
authors.initials: P
authors.lastname: Wallemacq
authors.forename: J P
authors.initials: JP
authors.lastname: Dehoux
authors.forename: D
authors.initials: D
authors.lastname: Latinne
mesh_terms: D000818:Animals; D001711:Biotransformation; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D007783:Lactones / Q000737:chemistry; D007959:Lymphocyte Culture Test, Mixed; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*; D008862:Microsomes, Liver / Q000378:metabolism*; D008958:Models, Molecular; D008968:Molecular Conformation; D009249:NADP / Q000378:metabolism; D010084:Oxidation-Reduction; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D013237:Stereoisomerism; D013552:Swine; D016559:Tacrolimus / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D007783:Lactones; D009249:NADP; D000068338:Everolimus; D020123:Sirolimus; D016559:Tacrolimus