Enantioselective HPLC of potentially CNS‐active acidic amino acids with a cinchona carbamate based chiral stationary phase

Abstract

A tert-butylcarbamoylquinine-based chiral stationary phase (Chiralpak QN-AX) has been employed for the enantiomer separation of underivatized chiral acidic amino acids, viz. 4-carboxyphenylalanine (4-CPHE), 1-aminoindan-1,5-dicarboxylic acid (AIDA), 2-(5-carboxy-3-methyl-2-thienyl)glycine (3-MATIDA), 2-(4-carboxy-5-methyl-2-thienyl)glycine (5-MATIDA), and 2-(2'-carboxy-3'-phenylcyclopropyl)glycine (PCCG). Some of the acidic amino acids have potential activity on the central nervous system and are thus of great interest. A stereoselective HPLC method that allows the baseline resolution of all the five test solutes has been developed. For that purpose the mobile phase composition (pH, organic modifier, and type) and flow rate were optimized. The final method makes use of mild elution conditions, namely methanol - 0.8 M ammonium acetate buffer (97.5:2.5; v/v) pH 5.5 which are also compatible with mass spectrometric detection.

Potential of adsorption isotherm measurements for closer elucidating of binding in chiral liquid chromatographic phase systems

“…Despite the large impact of the additive it is often neglected in binding studies because no good method has been available to account for the additive which is invisible for traditional detectors. However, recently a convenient way to use the IM to numerically account for the invisible additive(s) in chiral preparative systems was proposed [20,59]. As will be seen by incorporation of the additive into the model, more optimal experimental conditions could be predicted for process optimization.…”

Resolution of Racemates and Enantioselective Analytics by Cinchona Alkaloids and Their Derivatives

“…Many synthetic and nonproteinogenous a-and b-amino acids 33-37 and their derivatives, including phenylglycines 33 [71], phenylalanines 34 [72,73], b-amino acids 35 [44,74,75] as well as prolines [76], 2-methyltaurine, GABA, and many b-methyl amino acids [77] were also successfully separated (Figure 13.13).…”

S-Trityl-(R)-Cysteine, a Multipurpose Chiral Selector for Ligand-Exchange Liquid Chromatography Applications

“…Besides the possibility of enantioseparating underivatized amino acids, which is particularly instrumental when only a small amount of sample is available, a series of other relevant advantages lead to favor the use of a CLEC methodology over the other chromatographic strategies allowing the separation of native, underivatized amino acids into their enantiomers (Berthod et al 1996;Hoffman et al, 2008Hoffman et al, , 2009Hyun, 2013;Sardella et al, 2008Sardella et al, , 2014aSardella et al, , 2014bYe et al, 2002). Among these, it is worth mentioning the generation of UV/vis-active metal complexes, which allows the detection of even UV-transparent molecules, and the use of commercially available and cost-effective chiral enantiodiscriminating agents, combined with rather inexpensive RP columns.…”