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.