Simultaneous enantioseparation and simulation studies of atenolol,metoprolol and propranolol on Chiralpak^■IG column using supercritical fluid chromatography  

作　　者：Pranav A.Pandya Priyanka A.Shah Pranav S.Shrivastav 

机构地区：[1]Department of Chemistry,School of Sciences,Gujarat University,Ahmedabad,380009,India

出　　处：《Journal of Pharmaceutical Analysis》2021年第6期746-756,共11页药物分析学报（英文版）

基　　金：Department of Chemistry,Gujarat University,for supporting this work;Human Resource Development GroupCouncil of Scientific&Industrial Research(CSIR),New Delhi,for Research Associate Fellowship(File No.:09/070(0058)2K18 EMR-I)。

摘　　要：Enantioseparation of threeβ-blockers,i.e.,atenolol,metoprolol and propranolol,was studied on amylose tris(3-chloro-5-methylphenylcarbamate)immobilized chiral stationary phase using supercritical fluid chromatography(SFC).The effect of organic modifiers(methanol,isopropanol and their mixture),column temperature and back pressure on chiral separation ofβ-blockers was evaluated.Optimum chromatographic separation with respect to resolution,retention,and analysis time was achieved using a mixture of CO_(2) and 0.1%isopropyl amine in isopropanol:methanol(50:50,V/V),in 75:25(V/V)ratio.Under the optimized conditions,the resolution factors(Rs)and separation factors(a)were greater than3.0 and 1.5,respectively.Further,with increase in temperature(25-45℃)and pressure(100-150 bars)there was corresponding decrease in retention factors(k),a and Rs.However,a reverse trend(a and Rs)was observed for atenolol with increase in temperature.The thermodynamic data from van’t Hoff plots revealed that the enantioseparation was enthalpy driven for metoprolol and propranolol while entropy driven for atenolol.To understand the mechanism of chiral recognition and the elution behavior of the enantiomers,molecular docking studies were performed.The binding energies obtained from simulation studies were in good agreement with the elution order found experimentally and also with the free energy values.The method was validated in the concentration range of 0.5-10μg/m L for all the enantiomers.The limit of detection and limit of quantitation ranged from 0.126 to 0.137μg/m L and 0.376-0.414μg/m L,respectively.The method was used successfully to analyze these drugs in pharmaceutical preparations.

关 键 词：ENANTIOSEPARATION Supercritical fluid chromatography Β-BLOCKERS Chiralpak^(■)IG column Molecular docking Binding energy 

分 类 号：R917[医药卫生—药物分析学]