Chiral microemulsion electrokinetic chromatography: Effect of cosurfactant identity on enantioselectivity, methylene selectivity, resolution, and other chromatographic figures of merit

Abstract

The effect of cosurfactant identity on microemulsion size, elution range, retention factor, enantioselectivity, methylene selectivity, efficiency, and resolution in chiral microemulsion formulations was examined. The chiral surfactant dodecoxycarbonylvaline was used in conjunction with the cosurfactants 1-butanol, 1-pentanol, 2-pentanol, 1-hexanol, 2-hexanol, cyclopentanol, and cyclohexanol. The millimolar concentration of cosurfactant was held constant regardless of identity. Ethyl acetate was incorporated as the microemulsion oil core and the buffer utilized was 50 mM phosphate at a pH of 7.0. In general, secondary alcohols improved enantioselectivities and primary alcohols had the opposite effect, with the exception of the 1-butanol. The trends observed varied slightly depending on analyte. Of the six chiral analytes tested, cyclopentanol provided the best enantioselectivity for three, 1-butanol for two compounds, and 2-pentanol for one analyte. The lowest enantioselectivities were achieved with 1-pentanol or 1-hexanol for all compounds. Methylene selectivity was found to decrease with reductions in alcohol chain length. Among equal carbon number alcohols, methylene selectivity was lower for secondary alcohols. Efficiency and resolution values varied with different cosurfactants and depended on analyte identity.

(S)-(+)-2-Octanol as a Chiral Oil Core for the Microemulsion Electrokinetic Chromatographic Separation of Chiral Basic Drugs

“…In addition to the use of a chiral surfactant [17][18][19][20][21][22] or a chiral cosurfactant 23 as the enantioselective element within the microemulsion droplets in MEEKC, the present study was demonstrated for a novel chiral-MEEKC system employing optically active (S)-(+)-2-octanol as a chiral oil for effecting the enantioseparation of basic drugs in MEEKC.…”

“…17,19,23 In addition, it is also recognized that organic modifiers can have an effect on the electroosmotic flow (EOF), the viscosity, the dielectric constant, the conductivity of the background electrolyte, and the solubility of the analytes. 27 Consequently, the effect of the 1-butanol concentration (4.4 to 8.8% (w/w)) on the enantioseparation of (±)-norephedrine was studied; and the obtained results can be seen in Fig.…”

“…Recently, many works have come up with a new kind of chiral emulsion in which a chiral surfactant (dodecoxycarbonylvaline) is incorporated in the microemulsion. [17][18][19][20][21][22] In addition, Zheng et al presented another novel chiral microemulsion for achieving chiral separations based on the use of chiral alcohol as a cosurfactant. 23 In this work, a new chiral-MEEKC system using (S)-(+)-2-octanol as an oil core was employed for the enantioseparation of basic drugs.…”

Review of aqueous chiral electrokinetic chromatography (EKC) with an emphasis on chiral microemulsion EKC

“…In addition, racemic 2-hexanol was tested as a cosurfactant and found to greatly improve efficiency over the previously used 1-butanol. Another DDCV study compared the effects of seven different achiral cosurfactants (primary, secondary, and cyclic alcohols at equimolar concentrations) on the enantioseparation of six pairs of pharmaceutical enantiomers [67]. The main trends identified were: higher enantioselectivity with cyclic and short chain primary alcohols (1-butanol and cyclopentanol), lower enantioselectivity with longer chain primary alcohols, largest overall efficiency with 1-hexanol, and largest overall resolution with 1-butanol.…”

Two‐chiral component microemulsion EKC – chiral surfactant and chiral oil. Part 2: Diethyl tartrate

“…The first such publication described chiral selectivity achieved by using an aggregate system consisting of an achiral surfactant, an achiral cosurfactant, and a chiral oil (dibutyl tartrate) [49]. Several investigations in chiral MEEKC have been performed by our group with the surfactant dodecoxycarbonylvaline (DDCV) serving as the only chiral selectand in the PSP formulation and have focused on variations of surfactant concentration [50], buffer identity [50], oil identity [51], temperature [52], and cosurfactant identity [53]. There has been one report where the chiral surfactant (polysodium N-undecenoyl-D-valinate, poly-D-SUV) was utilized in two ways for chiral EKC: (i) cosurfactant and oil phases were added to poly-D-SUV micelles to form a microemulsion solution and (ii) the surfactant was polymerized under microemulsion conditions and subsequently employed under nonmicroemulsion conditions as the material was rotavaporized and freeze-dried prior to dissolution in buffer [54].…”