1: J Mass Spectrom  2001 Aug;36(8):889-901

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.

Lhoest G, Hertsens R, Verbeeck RK, Maton N, Wallemacq P, Dehoux JP, Latinne D.

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

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. Copyright 2001 John Wiley
& Sons, Ltd.

PMID: 11523088 [PubMed - indexed for MEDLINE]