A Validated Direct Thin-Layer Chromatographic Separation and Enantioselective Determination of Racemic Centrally Acting Drugs Using Ion-Pair and Ligand-Exchange Chiral Selectors: A Thermodynamic Study of Complexation

A rapid, inexpensive, and stereoselective densitometric-thin-layer chromatographic (TLC) method using L-(+)-tartaric acid and L-histidine-Cu complex as chiral mobile phase additive for the enantioseparation of atracurium besylate and atropine sulfate, respectively, and quantitative determination of their chiral switching (eutomer) isomers, cisatracurium besylate and hyoscyamine sulfate, were used in this study. The effect on resolution of different chiral selector concentrations, temperatures, and pH values was investigated. The spots were detected with ultraviolet (UV) lamp followed by densitometric measurements at 280 nm and 215 nm for cisatracurium besylate and hyoscyamine sulfate, respectively. The mobile phases enabling successful resolution were acetonitrile-methanol-dichloromethane-glacial acetic acid-H2O containing 70 mg L-(+)-tartaric acid (7:1:0.5:0.7:1, by volume), pH 5 for atracurium besylate, and methanol-H2O containing 40 mmol L-histidine and 20 mmol copper(II) acetate (8.8:1.2, by volume), pH 6.5 for atropine sulfate. Thermodynamic parameters, enthalpy Delta H and entropy Delta S were investigated to study the effect of temperature on the enantioseparation using the Van't Hoff plot.