Differential effects of organic modifiers on the enantioseparation of dimetindene maleate with carboxymethyl‐β‐cyclodextrin in capillary electrophoresis

Abstract

Methanol enhances the enantioresolution of dimetindene enantiomers with carboxymethyl-beta-cyclodextrin (CMCD) as chiral selector at a concentration below its optimal value. The same effect was observed with ethanol (EtOH), although less pronounced. On the other hand, the addition of isopropanol (IP) or acetonitrile (ACN) decreases the enantioseparation. To elucidate the underlying mechanisms of these observed effects, other neutral (beta-CD, hydroxypropyl-beta-CD, and trimethyl-beta-CD) as well as chargeable (carboxyethyl-beta-CD and succinyl-beta-CD) CD derivatives were also tested with MeOH as organic modifier. It can be concluded that the increased enantioresolution of dimetindene enantiomers was only noted with CMCD as chiral selector and a short-chain organic modifier containing an alcohol function. The slight deprotonation of CMCD at pH 3.0 was only partly responsible for the high enantioselectivity and the 'favourable' effect of MeOH or EtOH. An important feature that can be concluded from these results is that for this particular analyte approximately the same resolution can be obtained with a lower CMCD concentration and the addition of some MeOH, compared to a MeOH free buffer.

Influence of methanol on the enantioresolution of antihistamines with carboxymethyl‐β‐cyclodextrin in capillary electrophoresis

“…These results confirm that maximal Dm can occur at lower CD concentrations than maximal resolution [13,37]. Important in these results is the fact that all tested antihistaminic drugs show an increase in enantio- 1, resolution improvement with organic modifier 6, slight improvement 2, decrease in resolution resolution with the addition of MeOH, as described for DM [17]. For CPM and CM, the same effect was seen with EtOH, although less pronounced.…”

“…TMCD behaved differently compared to the other CD derivatives. The addition of MeOH decreased the resolution but at higher concentrations of this solvent, an increase was observed, as is also described for DM [17]. Probably the high viscosities of the BGE caused these phenomena since high concentrations of TMCD were added to obtain the enantioseparation [26].…”

“…In previous work [17], the influence of the addition of an organic modifier on the enantioresolution of DM with various CDs was studied. To further elucidate the observed phenomena, other antihistamines were selected, namely CM, brompheniramine maleate (BPM), chlorpheniramine maleate (CPM), and pheniramine maleate (PM).…”

“…The concentrations of CD used in the design depended on the type of CD and were experimentally defined. The choice was based upon their chiral separation ability (complete enantioresolution with concentrations below the optimal value) and not too long migration times [17]. The nine experiments of the design were performed in a random order for each CD and organic modifier.…”

“…This should increase the difference in electrophoretic mobility between the free and the complexed forms of the analyte enantiomers [6,8,18,24]. However, it was shown for DM [17] that the slight deprotonation of the carboxylic function was only partly responsible and that other mechanisms may also play a role.…”