Enantioseparation of (RS)‐Propranolol by Chiral High-Performance-Liquid-Chromatography to Optimize its Therapeutic Profile

Abstract Propranolol is one of the most important beta-blocker drugs, it is an optically active compound that is marketed as a racemate, but its desired activity resides in the S-enantiomer which is about 100 times more potent than R-Propranolol. This paper describes an enantioseparation of (RS)‐Propranolol by HPLC Chiral using β-Cyclodextrin Chiral stationary phase (250 mm X 4 mm X 5 μm) with mobile phase composed of Acetonitrile: Ethanol: Acetic acid: Triethylamine (960: 40: 4: 3 v/v/v/v), at a flow rate of 1 mL/min. Detection was made by ultraviolet absorption at 225 nm. The retention time of S-Propranolol and R-Propranolol was respectively: 16.18 min and 18.50 min.The racemic Propranolol contains 50.43 %of S-Propranolol and 49.57 % of R-Propranolol. The enantiomeric purity equals to 50.43 % and the enantiomeric excess equals to 0.86 %. The specific rotary power of (RS)-Propranolol racemic solution was +17 deg·dm–1·g–1·mL and the optical rotation angle α was between [-1.0 ° and +1.0 °] which shows that the racemic mixture has deflected the polarized light on the right, which deduces that (RS)-Propranolol racemic isn’t an equimolar mixture. So, for a selective β-blocking use, it could be very interesting to encourage the production of Propranolol in its form enantiomerically pure which is the S-enantiomer by chiral separation to find an optimal treatment and a right therapeutic control for the patient.

Keywords Enantioseparation, Propranolol, β-blocker, HPLC Chiral, β-Cyclodextrin, Racemate.

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Updated: January 20, 2024 — 7:51 am