Direct, Preparative Enantioselective Chromatography of Propranolol Hydrochloride and Thioridazine Hydrochloride Using Carbon Dioxide-based Mobile Phases

In this paper, we describe the direct, preparative enantioselective chromatography of racemic (rac)-propranolol hydrochloride (HCI) and rac-thioridazine.HCl using Chiralpak AD chiral stationary phase and mobile phase systems containing carbon dioxide and methanol without the use of basic or acidic additives. Isolated fractions of propranolol.HCl were positively identified by mass spectrometry, Beilstein flame test, melting point, and chemical analysis to be HCI enantiomers of propranolol-HCl salts exhibited characteristic mass spectra peaks at 36 and 38 mass-to-charge ratio in the expected 3:1 isotopic ratio for the solute that were absent in the mass spectra for the free-base forms. To our knowledge, the direct, preparative enantioselective isolation of HCI enantiomeric salts of rac-propranolol and of rac-thioridazine have not been previously demonstrated and published.