Sensitive chiral high-performance liquid chromatographic assay for labetalol in biological fluids.
The four stereoisomers of the combined alpha- and beta-adrenoceptor antagonist labetalol were separated and quantified at therapeutic concentrations by normal-phase high-pressure liquid chromatography using a chiral stationary phase and fluorescence detection. Drug in plasma or urine was recovered by solid-phase extraction with 83+/-5% efficiency. Limits of detection from biological samples (3 ml) were between 1.5-1.8 ng ml(-1). Intra-day and inter-day variation at 25 ng ml(-1) were < or = 2.7% and < or = 5.80% respectively for all stereoisomers. The assay was applied to an examination of the disposition of labetalol stereoisomers after a single oral dose of racemate to a human volunteer. Labetalol appears to undergo enantioselective metabolism leading to relatively low plasma concentrations of the pharmacologically active enantiomers.
Dakers
J M
JM
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Boulton
D W
DW
Fawcett
J P
JP
D000319:Adrenergic beta-Antagonists / Q000032:analysis* / Q000493:pharmacokinetics; D000328:Adult; D001826:Body Fluids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D007700:Kinetics; D007741:Labetalol / Q000032:analysis* / Q000493:pharmacokinetics; D008297:Male; D008832:Microchemistry; D013237:Stereoisomerism
D000319:Adrenergic beta-Antagonists; D007741:Labetalol