Analytical enantioseparation of N‐alkyl drugs by reversed‐phase liquid chromatography with carboxymethyl‐β‐cyclodextrin as mobile phase additive

Carboxymethyl-β-cyclodextrins (CM-β-CDs) with five kinds of degrees of substitution were synthesized and characterized. Analytical enantioseparation of six basic drugs containing N-alkyl groups, including pheniramine, chlorpheniramine, labetalol, propranolol, venlafaxine, and trans-paroxol, was achieved by reversed-phase high-performance liquid chromatography (RP-HPLC) using the synthesized CM-β-CD as chiral mobile phase additives. Key influence factors were optimized, including organic modifier, pH value, CM-β-CD with different degrees of substitution, and concentration of CM-β-CD. The mobile phase was composed of methanol and 10 mmol L-1 of phosphate buffer pH 4.0 containing 10 mmol L-1 of CM-β-CD. Peak resolution for six racemic drugs was gradually increased with an increasing degree of substitution of the synthesized CM-β-CD. The stoichiometric ratio and binding constants for the inclusion complex formed by CM-β-CD and enantiomer were determined, which showed that the stoichiometric ratio for each inclusion complex was 1:1.