The chlorpheniramine enantiomers were separated with capillary zone electrophoresis using β-cyclodextrin as the chiral selector.The effects of the concentration of β-cyclodextrin, the electrolyte pH and organic modi...The chlorpheniramine enantiomers were separated with capillary zone electrophoresis using β-cyclodextrin as the chiral selector.The effects of the concentration of β-cyclodextrin, the electrolyte pH and organic modifier(urea) on the difference in apparent electrophoretic mobilities of the enantiomels were investigated.展开更多
This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel α- and β-receptor blocking agent, 1-[4-（2-methoxyethyl） phenoxy]-3-...This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel α- and β-receptor blocking agent, 1-[4-（2-methoxyethyl） phenoxy]-3-[[2-（2- methoxyphenoxy） ethyl]amino]-2-propanol （T J0711）, in rat plasma. GITC was used for precolunm derivatization of T J0711 enantiomers. Enantiomeric resolution was achieved on a Eurospher-100 C18 column （250 mm×4.6 mm ID, 5-μm particle size）, with UV detection at 255 nm, and the mobile phase consisted of acetonitrile and water （58：42, v/v） containing 0.02% glacial acetic acid （v/v）. Using the chromatographic conditions described, T J0711 enantiomers were well resolved with mean retention time of 10.2 and 11.5 min, respectively. Linear response （r〉0.999） was observed over the range of 0.125-12.5 μg/mL of TJ0711 hydrochloride enantiomers. The mean relative standard deviation （RSD%） of the results of within-day precision was ≤ 10%. The proposed method was found to be suitable and accurate for the quantitative determination of T J0711 enantiomers in rat plasma, and it can be used in pharmacokinetic studies.展开更多
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>r...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 α;-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.展开更多
文摘The chlorpheniramine enantiomers were separated with capillary zone electrophoresis using β-cyclodextrin as the chiral selector.The effects of the concentration of β-cyclodextrin, the electrolyte pH and organic modifier(urea) on the difference in apparent electrophoretic mobilities of the enantiomels were investigated.
基金supported by a grant from a science andtechnology research program of Hubei provincial government(No.2003AA301B05)the Wuhan New Drug Development Program(No.20066002103)
文摘This investigation describes a new precise, sensitive and accurate stereoselective RP-HPLC method for determination of the enantiomers of a novel α- and β-receptor blocking agent, 1-[4-（2-methoxyethyl） phenoxy]-3-[[2-（2- methoxyphenoxy） ethyl]amino]-2-propanol （T J0711）, in rat plasma. GITC was used for precolunm derivatization of T J0711 enantiomers. Enantiomeric resolution was achieved on a Eurospher-100 C18 column （250 mm×4.6 mm ID, 5-μm particle size）, with UV detection at 255 nm, and the mobile phase consisted of acetonitrile and water （58：42, v/v） containing 0.02% glacial acetic acid （v/v）. Using the chromatographic conditions described, T J0711 enantiomers were well resolved with mean retention time of 10.2 and 11.5 min, respectively. Linear response （r〉0.999） was observed over the range of 0.125-12.5 μg/mL of TJ0711 hydrochloride enantiomers. The mean relative standard deviation （RSD%） of the results of within-day precision was ≤ 10%. The proposed method was found to be suitable and accurate for the quantitative determination of T J0711 enantiomers in rat plasma, and it can be used in pharmacokinetic studies.
基金supported by National Major Projects of Ministry Science and Technology of China(2011CB710800,2012ZX09506001-004)Zhejiang Education Department(Y200909571)
文摘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 α;-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.
