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

Abstract 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.