Yi-Hong Tang, Jun-Yan Wang, Hai-Hong Hu, Tong-Wei Yao, Su Zeng. Analysis of species-dependent hydrolysis and protein binding of esmolol enantiomers[J]. Journal of Pharmaceutical Analysis, 2012, 02(3): 220-225. doi: 10.1016/j.jpha.2012.01.007
Citation:
Yi-Hong Tang, Jun-Yan Wang, Hai-Hong Hu, Tong-Wei Yao, Su Zeng. Analysis of species-dependent hydrolysis and protein binding of esmolol enantiomers[J]. Journal of Pharmaceutical Analysis, 2012, 02(3): 220-225. doi: 10.1016/j.jpha.2012.01.007
Yi-Hong Tang, Jun-Yan Wang, Hai-Hong Hu, Tong-Wei Yao, Su Zeng. Analysis of species-dependent hydrolysis and protein binding of esmolol enantiomers[J]. Journal of Pharmaceutical Analysis, 2012, 02(3): 220-225. doi: 10.1016/j.jpha.2012.01.007
Citation:
Yi-Hong Tang, Jun-Yan Wang, Hai-Hong Hu, Tong-Wei Yao, Su Zeng. Analysis of species-dependent hydrolysis and protein binding of esmolol enantiomers[J]. Journal of Pharmaceutical Analysis, 2012, 02(3): 220-225. doi: 10.1016/j.jpha.2012.01.007
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University
Hangzhou, Zhejiang 310058, People's Republic of China
Shanghai Institute of Technology, Shanghai 201418, People's Republic of China
Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University,Hangzhou, Zhejiang 310058, People's Republic of China
Funds:
National Major Projects of Ministry Science and Technology of China
The stereoselective hydrolysis of esmolol in whole blood and in its separated components from rat,rabbit and human was investigated.Blood esterase activities were variable in different species in the order of rat > rabbit > human.Rat plasma showed the high esterase activity and had no stereoselectivity to enantiomers.Rabbit red blood cell (RBC) membrane,RBC cytosol and plasma all hydrolyzed esmolol but with different esterase activity,whereas the hydrolysis in RBC membrane and cytosol showed significant stereoselectivity towards R-(+)-esmolol.Esterase in RBC cytosol from human blood mainly contributed to the esmolol hydrolysis,which was demonstrated with no stereoselctivity.Esterase in human plasma showed a low activity,but a remarkable stereoselectivity with R-(+)-esmolol.In addition,the protein concentration affected the hydrolysis behavior of esmolol in RBC suspension.Protein binding of esmolol enantiomers in human plasma,human serum albumin (HSA) and α1-acid glycoprotein (AGP) revealed that there was a significant difference in bound fractions between two enantiomers,especially for AGP.Our results indicated that the stereoselective protein binding might play a role in the different hydrolysis rates of esmolol enantiomers in human plasma.