Stereoselective hydrolysis of O-acetyl propranolol as prodrug in human serum.
A direct high-performance liquid chromatographic method was developed for the assays of the enantiomers of O-acetyl propranolol. Using this procedure, the stereochemical characteristics on hydrolysis of racemic O-acetyl propranolol as a prodrug have been studied in phosphate buffer (pH 7.4) and in 90% human serum. In the phosphate buffer, no difference in the hydrolysis rate between the esters of (R)- and (S)-propranolol was observed. In 90% human serum, the hydrolysis of the esters was accelerated, and the hydrolysis rate of the ester of (R)-isomer was about three times faster than that of the ester of (S)-isomer. The interconversion between (R)- and (S)-isomer was not observed during the hydrolysis of prodrug in buffer and in human serum. These results indicated that hydrolysis of O-acetyl propranolol occurs stereoselectively in human serum.
Takahashi
K
K
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
Haginaka
J
J
Tamagawa
S
S
Nishihata
T
T
Yasuda
H
H
Katagi
T
T
D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D011355:Prodrugs; D011433:Propranolol / Q000031:analogs & derivatives* / Q000097:blood; D013237:Stereoisomerism
D011355:Prodrugs; C066044:O-acetylpropranolol; D011433:Propranolol