Enantioselective drug monitoring of (R)- and (S)- propranolol in human plasma via derivatization with optically active (R,R)-O,O-diacetyl tartaric acid anhydride.
A sensitive high-performance liquid chromatographic method was developed for the stereoselective assay of (R)- and (S)-propranolol in human plasma. The method involves diethyl ether extraction of the drugs and a racemic internal standard, N-tert.-butylpropranolol, followed by derivatization of the compounds with the chiral reagent (R,R)-O,O-diacetyl tartaric acid anhydride. The resulting diastereomeric derivatives were separated isocratically on a reversed-phase column. Quantitation was achieved by the peak-height ratio method with reference to the internal standard. The assay was accurate and reproducible in the concentration range 1-100 ng of (R)- and (S)-propranolol per ml plasma, using fluorescence detection at lambda ex 290 nm and lambda em 335 nm. The applicability of this method was demonstrated for the determination of concentration-time profiles of propranolol enantiomers in the course of comparative pharmacokinetic studies.
Lindner
W
W
Institute of Pharmaceutical Chemistry, Karl-Franzens University of Graz, Austria.
Rath
M
M
Stoschitzky
K
K
Uray
G
G
D000284:Administration, Oral; D000812:Anhydrides; D005260:Female; D006801:Humans; D007202:Indicators and Reagents; D008297:Male; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D013237:Stereoisomerism; D013644:Tartrates
D000812:Anhydrides; D007202:Indicators and Reagents; D013644:Tartrates; C059721:O,O-diacetyl tartaric acid anhydride; D011433:Propranolol