Takahashi K, Haginaka J, Tamagawa S, Nishihata T, Yasuda H, Katagi T
Faculty of Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
J Pharm Pharmacol. 1990 May;42(5):356-7. doi: 10.1111/j.2042-7158.1990.tb05427.x.
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.
建立了一种直接高效液相色谱法用于测定O-乙酰普萘洛尔对映体。采用该方法，研究了外消旋O-乙酰普萘洛尔作为前药在磷酸盐缓冲液（pH 7.4）和90%人血清中的水解立体化学特征。在磷酸盐缓冲液中，未观察到（R）-和（S）-普萘洛尔酯水解速率的差异。在90%人血清中，酯的水解加速，（R）-异构体酯的水解速率约为（S）-异构体酯的三倍。在前药在缓冲液和人血清中的水解过程中未观察到（R）-和（S）-异构体之间的相互转化。这些结果表明O-乙酰普萘洛尔在人血清中的水解具有立体选择性。
