Simultaneous determination of propranolol enantiomers in plasma by high-performance liquid chromatography with fluorescence detection.
A simple, rapid, and sensitive assay for the simultaneous quantification of the (-)- and (+)-propranolol in human and dog plasma is described using a reversed-phase high-performance liquid chromatography (HPLC) system with fluorescence detection. The method involves extraction of propranolol enantiomers from plasma into 1% 1-butanol in n-hexane at basic pH, followed by evaporation of the organic phase and the formation of diastereomeric derivatives with the chiral reagent (-)-menthyl chloroformate. (+)-Flecainide is used as the internal standard. The limiting concentration of each enantiomer that can be detected is 1 ng/mL plasma. In six normal human volunteers, who received a single oral dose of 80 mg of racemic propranolol, the plasma levels of the (-)-enantiomer were always higher than those of the (+)-enantiomer with a mean (-):(+) ratio of 1.38. The half-lives of both the enantiomers were similar (3.5 +/- 0.3 h). In six normal male mongrel dogs given a single intraportal dose of 40 mg of racemic propranolol, the plasma levels of the (-)-enantiomer were always lower than those of the (+)-enantiomer with a mean (-):(+) ratio of 0.48. The half-life of the (-)-enantiomer (73.3 +/- 16.2 min) was shorter than that of the (+)-enantiomer (87.1 +/- 18.1 min).
Prakash
C
C
Department of Pharmacology, Vanderbilt University, School of Medicine, Nashville, TN 37232.
Koshakji
R P
RP
Wood
A J
AJ
Blair
I A
IA
D000328:Adult; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D006207:Half-Life; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D011433:Propranolol / Q000097:blood*; D011786:Quality Control; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
D011433:Propranolol