STEREOSELECTIVITY OF THE IN-VITRO METABOLISM OF THALIDOMIDE

The stereoselective metabolism of the former sedative thalidomide and the metabolism of its analogue EM 12 were studied in vitro with liver homogenates. In our study we focused on hydroxylated nonhydrolyzed met abolites of thalidomide. An analytical HPLC method was developed to de termine these metabolites directly. The investigations showed a highly stereoselective biotransformation of thalidomide. 5-Hydroxy thalidomi de was preferentially formed by (-)-(S)-thalidomide, whereas (+)-(R)-t halidomide was metabolized to two hitherto unknown compounds (Met A an d B). Mass spectrometry of these metabolites Met A and B indicated tha t oxidation or hydroxylation took place in the glutarimide moiety. Bio transformation studies with the more stable thalidomide analogue EM 12 revealed four new metabolites (Met C-F) whose quantities differed in the selected liver homogenate. (C) 1994 Wiley-Liss, Inc.