Determination of (R)-AND (S)-alprenolol-and (R)- and (S)-metoprolol as their diastereomeric derivatives in human plasma by reversed-phase liquid chromatography.
A high-performance liquid chromatographic method is described for the determination of (R)- and (S)-alprenolol and (R)- and (S)-metoprolol in human plasma. Separation of the enantiomers was accomplished after preparation of diastereomeric derivatives with symmetrical anhydrides of tert.-butoxycarbonyl-L-leucine followed by treatment with trifluoroacetic acid at 0 degree C to remove the tert.-butoxycarbonyl group. The separations of the diastereomeric derivatives were performed using a reversed-phase system with muBondapak C18 as support and phosphate buffer pH 3.0 with the addition of acetonitrile as the mobile phase. High stability of the chromatographic system was achieved. The reproducibilities in the determination of (R)- and (S)-alprenolol and (R)- and (S)-metoprolol in human plasma were 9.4 and 9.8% (relative standard deviation) for alprenolol and metoprolol, respectively, at drug levels of 0.5 ng/ml. In two subjects who received single oral doses of alprenolol (100-mg tablet) and metoprolol (50-mg tablet) the plasma levels of the (R)-isomers were lower than for the (S)-isomers.
D000526:Alprenolol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D007700:Kinetics; D008790:Metoprolol / Q000031:analogs & derivatives / Q000097:blood*; D011412:Propanolamines / Q000097:blood*; D012016:Reference Values; D013237:Stereoisomerism; D013997:Time Factors
D011412:Propanolamines; D000526:Alprenolol; D008790:Metoprolol