title: Simultaneous determination of propranolol and 4-hydroxypropranolol enantiomers after chiral derivatization using reversed-phase high-performance liquid chromatography.
abstract: A reversed-phase high-performance liquid chromatographic method is described, which allows the simultaneous quantification of propranolol and 4-hydroxypropranolol enantiomers in human plasma. After extraction from plasma (pH 10.5) using ethyl acetate, the enantiomers are derivatized with R-(+)-phenylethylisocyanate as chiral derivatization reagent and triethylamine as basic catalyst in chloroform. Ascorbic acid is used to prevent 4-hydroxypropranolol from oxidation during the extraction. Chromatographic separation on ODS columns and fluorescence detection (228 nm/greater than 340 nm) allows sensitive quantitation of all derivatives. Incubation of the plasma samples with beta-glucuronidase/arylsulfatase and the use of the specific beta-glucuronidase inhibitor saccharo-1,4-lactone allows the quantitation of both the sulfate and glucuronide conjugates of the enantiomers. The method was applied to human plasma samples from a subject after administration of 60 mg racemic propranolol three times daily.
authors.affiliation: Department of Pharmaceutics, University of Florida, Gainesville 32610.
authors.forename: H G
authors.initials: HG
authors.lastname: Schaefer
authors.forename: H
authors.initials: H
authors.lastname: Spahn
authors.forename: L M
authors.initials: LM
authors.lastname: Lopez
authors.forename: H
authors.initials: H
authors.lastname: Derendorf
mesh_terms: D000818:Animals; D001192:Arylsulfatases; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003485:Cyanates; D004285:Dogs; D005021:Ethylamines; D005965:Glucuronates / Q000097:blood; D005966:Glucuronidase; D006801:Humans; D017953:Isocyanates; D008297:Male; D011433:Propranolol / Q000031:analogs & derivatives* / Q000097:blood* / Q000652:urine; D013237:Stereoisomerism; D013431:Sulfates / Q000097:blood
chemical_list: D003485:Cyanates; D005021:Ethylamines; D005965:Glucuronates; D017953:Isocyanates; D013431:Sulfates; C020790:phenylethyl isocyanate; C001422:4-hydroxypropranolol; D011433:Propranolol; D001192:Arylsulfatases; D005966:Glucuronidase; C016162:triethylamine