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Glucuronidation of labetalol at the two hydroxy positions by bovine liver microsomes. Isolation, purification, and structure elucidation of the glucuronides of labetalol

NR Niemeijer, TK Gerding and RA De Zeeuw

Laboratory Diephuis, Groningen, The Netherlands.

Glucuronidation is known to be a major metabolic pathway for labetalol. As the drug contains a phenolic and an alcoholic hydroxy group, in principle two regio isomeric glucuronides can be formed. By incubating the substrate labetalol with bovine liver microsomes, in the presence of the co-substrate UDP-glucuronic acid, both hydroxy positions were glucuronidated. The different glucuronides were isolated from the incubation mixture using Bond-Elut extraction cartridges and separated by means of high performance liquid chromatography. The formation of glucuronides was confirmed by performing reference incubations using radiolabeled UDP-glucuronic acid. Structure elucidation of the various glucuronides was done by nuclear magnetic resonance, ultraviolet spectroscopy, and mass spectrometry.

Volume 19, Issue 1, pp. 20-23, 01/01/1991
Copyright © 1991 by American Society for Pharmacology and Experimental Therapeutics




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Copyright © 1991 by the American Society for Pharmacology and Experimental Therapeutics.