title: Aromatic hydroxylation of oxprenolol. Quantitation and stereoselectivity in the formation of 4'- and 5-hydroxyoxprenolol in vivo in the rat.
abstract: Aromatic hydroxylation of oxprenolol administered ip to rats produced 4'- and 5-hydroxyoxprenolol in 9.4% and 2.8% of the administered dose, in a ratio of ca. 3.5 to 1, as determined after deconjugation of the urinary metabolites by 8-glucuronidase. After HPLC separation, the metabolites were determined by mass spectral (CIMS) techniques using specifically deuterated 4'- and 5'-hydroxyoxprenolol-d2 as standards. From in vivo metabolic experiments using a pseudoracemate of oxprenolol prepared from (2R)-oxprenolol-d2 and (2S)-oxprenolol-d0, greater 4'-hydroxylation of the (2R)-enantiomer was shown to occur by 3.1 fold, and greater 5'-hydroxylation also of the (2R)-enantiomer occured by 1.4 fold. These results could occur because of stereoselectivity in the metabolic hydroxylation process and/or could reflect possible enantiomeric enrichment of the oxprenolol presented to the liver due to stereoselective tissue binding of the (2S)-enantiomer or could be due to stereoselectivity in the metabolism of oxprenolol by one or more competing pathways.
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D006900:Hydroxylation; D013058:Mass Spectrometry; D010096:Oxprenolol / Q000032:analysis / Q000378:metabolism*; D011433:Propranolol / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism
chemical_list: D010096:Oxprenolol; D011433:Propranolol