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(...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.展开更多
建立了一种快速、准确的高效液相色谱分析方法。使用Chiralpak AD-H手性色谱柱,检测波长224nm,考察了流动相中极性调节剂的体积分数、流动相中三乙胺的体积分数、柱温及流速对西那卡塞对映体拆分的影响。确立了最佳拆分条件:流动相为正...建立了一种快速、准确的高效液相色谱分析方法。使用Chiralpak AD-H手性色谱柱,检测波长224nm,考察了流动相中极性调节剂的体积分数、流动相中三乙胺的体积分数、柱温及流速对西那卡塞对映体拆分的影响。确立了最佳拆分条件:流动相为正己烷-异丙醇-三乙胺(90∶10∶0.1,V/V/V);流速为1.0 m L·min-1;柱温为30℃。在此优化实验条件下,得到西那卡塞对映体的出峰顺序为:先S体,后R体。所建立的方法简单准确,重复性好,可用于西那卡塞的质量研究和控制。展开更多
目的建立简便、灵敏的手性高效液相色谱法检查苄基依折麦布中的异构体杂质。方法以Chiralpak IC为固定相,正己烷-异丙醇(体积比90∶10)为流动相,流速为1.0 m L·min-1,检测波长为232 nm。结果通过对分离条件进行优化,苄基依折麦...目的建立简便、灵敏的手性高效液相色谱法检查苄基依折麦布中的异构体杂质。方法以Chiralpak IC为固定相,正己烷-异丙醇(体积比90∶10)为流动相,流速为1.0 m L·min-1,检测波长为232 nm。结果通过对分离条件进行优化,苄基依折麦布与其异构体杂质能达到良好分离。苄基依折麦布在质量浓度为1.0~12 mg·L-1内线性关系良好。平均回收率为99.8%,日内与日间精密度均小于3.0%。结论所建立的分析方法灵敏度高、重现性好,适用于苄基依折麦布中异构体杂质的检查。展开更多
基金Department of Chemistry,Gujarat University,for supporting this workHuman Resource Development GroupCouncil of Scientific&Industrial Research(CSIR),New Delhi,for Research Associate Fellowship(File No.:09/070(0058)2K18 EMR-I)。
文摘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.
文摘建立了一种快速、准确的高效液相色谱分析方法。使用Chiralpak AD-H手性色谱柱,检测波长224nm,考察了流动相中极性调节剂的体积分数、流动相中三乙胺的体积分数、柱温及流速对西那卡塞对映体拆分的影响。确立了最佳拆分条件:流动相为正己烷-异丙醇-三乙胺(90∶10∶0.1,V/V/V);流速为1.0 m L·min-1;柱温为30℃。在此优化实验条件下,得到西那卡塞对映体的出峰顺序为:先S体,后R体。所建立的方法简单准确,重复性好,可用于西那卡塞的质量研究和控制。