Glucuronidation of labetalol at the two hydroxy positions by bovine liver microsomes. Isolation, purification, and structure elucidation of the glucuronides of labetalol.
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.
Niemeijer
N R
NR
Laboratory Diephuis, Groningen, The Netherlands.
Gerding
T K
TK
De Zeeuw
R A
RA
D000818:Animals; D002417:Cattle; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000302:isolation & purification / Q000378:metabolism; D007741:Labetalol / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D014535:Uridine Diphosphate Glucuronic Acid / Q000378:metabolism
D005965:Glucuronates; D014535:Uridine Diphosphate Glucuronic Acid; D007741:Labetalol