Enantioseparations simultaneous

Cherkaoui, S., and Veuthey, J. L. (2001). Use of negatively charged cyclodextrins for the simultaneous enantioseparation of selected anesthetic drugs by capillary electrophoresis-mass spectrometry. /. Pharm. Biomed. Anal. TJ, 615 — 626. 

Zheng, J., and Shamsi, S. A. (2006). Simultaneous enantioseparation and sensitive detection of eight p-blockers using capillary electrochromatography-electrospray ionization-mass spectrometry. Electrophoresis 27, 2139—2151. 

Since one or more of the interactions in these systems might originate from the stationary phase, only a two- or a one-point interaction between the solute and the selector is necessary for mechanisms (2) and (3) to occur [50]. However, some of the CMPAs used in HPLC [37,40,51,52] have also been used as chiral selectors in CE [53-56], which indicates that at least one of the separation mechanisms between the selector and enantiomers is selective complex formation in the mobile phase in these cases, since there is no stationary phase present in CE. A recent example by Yuan et al. [57] is presented in Eigure 17.1. The authors introduced the use of (R)-A,A,A-trimethyl-2-aminobutanol-bis(trifluoromethane-sulfon)imidate as the chiral selector for enantioseparation in HPLC, CE, and GC. This chiral liquid serves simultaneously as a chiral selector and a co-solvent. 

The effect of surface polarity is even more important in separations where two or more simultaneous interactions must occur in order to achieve the desired selectivity. This is particularly true in chiral separations. Since aqueous buffer systems are almost universally used as CEC mobile phases, enantioseparations are often run under re-versed-phase conditions as opposed to the normal-phase mode typically used in chiral HPLC. Therefore, non-specific hydrophobic interactions would be highly detrimental to the discrimination process that involves subtle differences between the enantiomers. 

Fig. 1 Simultaneous separation and enantioseparation of thalidomide, 5-hydroxythalidomide, and 5 -hydroxythalidomide in CE using polyacrylamide-coated capillary and a mixture of 15 mg/mL sulfobutyl (4.0)-/3-CD and 10 mg/mL (3-CD as the chiral carrier.

Successful enantioseparation of individual N -protected amino acids stimulated the development of a rapid method of their simultaneous enantioseparation and quantification in a mixture. A feasibility study on this topic has been recently published by Welsch et al. [69]. The two-dimensional HPLC method involves online coupling of a narrow-bore C18 reverse phase (RP) column in the first dimension (separation of racemic amino acids) to a short enantioselective column based on nonporous 1.5 pm particles modified with t-BuCQD in the second dimension (determination of enantiomer composition). Using narrow-bore column resulted in fast analysis time for example, the mixture of nine racemic N-DNB-protected amino acids was completely analyzed within 16 min. 

Zhou, L. Thompson, R. French, M. Ellison, D. Wyvratt, J. Simultaneous enantioseparation of a basic drug compound and its acidic intermediate by capillary electrophoresis. J. Sep. Sci. 2002, 25, 1183-1189. 

Uray, G., Kosjek, B. Simultaneous enantioseparation of flobufen and its diastereomeric metabolites on ULMO, a pirkle type chiral stationary phase. Enantiomer, 2000, 5, 329-332. 

Phinney et al. developed three CE-UV methods that allowed the enantiose-paration of ephedrine and pseudoephedrine using neutral HP-pCD, DM-pCD, and charged sulfated pCD as chiral selectors. The combination of negatively charged sulfated pCD (2.8 %) and DM-pCD (1.2 %) under acidic conditions (pH 2.5) provided the best separation of the two couples of enantiomers. Standard reference materials (SRMs) containing ephedra in development at NIST were analyzed by each of three CE methods. In the SRM samples, only the naturally occurring enantiomers ( )-ephedrine and (-l-)-pseudoephedrine were found however, the method proved to be suitable in detecting product adulteration by its potential in identification of specific stereoisomers [56]. The neutral HP-pCD was also found to be a useful chiral selector in the presence of tetrabutylammonium chloride as additive, for the simultaneous enantioseparation of ephedrine, pseudoephedrine, iV-methylephedrine, and norephedrine enantiomers in Ephedra sinica extracts [57]. 

Although SDS is the most versatile and useful micellar agent, different surfactants can be introduced in MEKC to gain specific selectivity. Interestingly, Hou et al. performed the simultaneous MEKC enantioseparation of four pairs of ephedrine related compounds, namely, ( )-ephedrine, ( )-pseudoephedrine, ( )-norephedrine, and ( )-A-methylephedrine, using a polymeric chiral surfactant, i.e., polysodium A-undecenoxycarbonyl-L-leucinate. Because of the high molecular mass of the surfactant, the BGE showed to be compatible with the online ESI-MS detection [91]. In Fig. 36.6, the effect of the chiral surfactant concentration on the separation of the studied analytes is shown. 

Kreidler D, Czesla H, Schurig V (2008) A mixed stationary phase containing two versatile cyclodextrin-based selectors for the simultaneous gas chromatographic enantioseparation of racemic alkanes and racemic a-amino add derivatives. J Chromatogr B 875 208-216... 

Fig. 5 Simultaneous carrier mode CE separation and enantioseparation of thalidomide and its hydroxylated metabolites (reproduced with permission from [43])...

Enantioselective gas chromatography was developed previously to liquid chromatography. Although GC was already a well-established separation technique when the interest for enantioseparation experienced an exponential growth, there has not been an explosion in CSP diversity like that seen with HPLC. The applicability of this technique, which is limited to thermostable and volatile compounds, and the simultaneous development of HPLC enantioseparation, may explain this observation. Nevertheless, many CSPs for GC are on the market, with the most used being those derived from amino acids and from cyclodextrins. 

In the case of our initial and unsuccessful TLC attempts to enantioseparate the 5,/ -( )-ibuprofen and the 5,/ -( )-2-phenylpropionic acid antipodes [1-3], we kept our test samples for a longer period of time dissolved in 70% ethanol (and also in dichloromethane and physiological salt). Evidently, none of these solvents can be considered as a base or an acid, at least not in the spirit of the acid and base definitions introduced by Arrhenius. In other words, none of these solvents can catalyze or hamper transenantiomerization of the chiral APAs. However, the 70% ethanol solvent can easily be viewed as a weak ampholyte, able to simultaneously exert the catalytic and inhibiting effect on transenantiomerization of the chiral analytes considered. Perhaps, this perceptible ampholytic nature of 70% ethanol (combined with a change in viscosity of the APA solutions, as related to that of... 

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