Simultaneous Enantioseparation and Simulation Studies of Some Drugs using Supercritical Fluid Chromatography


  • Nidhi Katiyar Research scholar, Department of Pharmacy, Sunrise University, Alwar Rajasthan.
  • Arun Sharma Research supervisor, Department of Pharmacy, Sunrise University, Alwar Rajasthan.




The enantioseparation of three b-blockers, namely atenolol, metoprolol, and propranolol, was investigated using supercritical fluid chromatography (SFC) on a chiral stationary phase immobilised with amylose tris(3-chloro-5-methylphenylcarbamate). An assessment was conducted to determine the impact of organic modifiers (methanol, isopropanol, and their combination), column temperature, and back pressure on the chiral separation of b-blockers. The best chromatographic separation in terms of resolution, retention, and analysis duration was obtained by utilising a combination of CO2 and 0.1% isopropyl amine in isopropanol: methanol (50:50, V/V), in a ratio of 75:25 (V/V).

When the settings were optimised, the resolution factors (Rs) and separation factors (a) were both higher than 3.0 and 1.5, respectively. Moreover, when the temperature (25e45 ◦C) and pressure (100e150 bars) increased, there was a commensurate drop in the retention factors (k), a, and Rs. Conversely, there was an opposite pattern found with atenolol as the temperature increased. The thermodynamic data obtained from van't Hoff plots indicated that the separation of enantiomers was primarily driven by changes in enthalpy for metoprolol and propranolol, while it was driven by changes in entropy for atenolol. Molecular docking experiments were conducted to provide insight into the process of chiral recognition and the elution behaviour of the enantiomers. The binding energies derived from simulation studies shown strong concordance with both the empirically determined elution sequence and the corresponding free energy values. The approach was verified within the concentration range of 0.5e10 mg/mL for all enantiomers. The range for the limit of detection was 0.126 to 0.137 mg/mL, while the range for the limit of quantitation was 0.376 to 0.414 mg/mL. The approach was effectively used to analyse these substances in pharmaceutical formulations.