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Chiral recognition in liquid chromatography utilising chargeable cyclodextrins for resolution of doxazosin enantiomers
Author(s) -
Owens Paul K.,
Fell Anthony F.,
Coleman Michael W.,
Berridge John C.
Publication year - 1997
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/(sici)1520-636x(1997)9:2<184::aid-chir20>3.0.co;2-i
Subject(s) - chemistry , enantiomer , doxazosin , chromatography , cyclodextrin , high performance liquid chromatography , chirality (physics) , selectivity , resolution (logic) , ionic liquid , tetrahydrofuran , stereochemistry , organic chemistry , solvent , nambu–jona lasinio model , chiral symmetry breaking , physics , quantum mechanics , quark , medicine , artificial intelligence , computer science , blood pressure , radiology , catalysis
The chromatographic resolution of rac‐doxazosin using reversed‐phase high performance liquid chromatography (HPLC) with the chargeable chiral mobile phase additive, carboxymethyl‐β‐cyclodextrin (CM‐β‐CD), is described. The effects of different modifiers (acetonitrile, methanol and tetrahydrofuran), pH, temperature, and cyclodextrin concentration were investigated to (a) assess the key chromatographic parameters for subsequent chemometric optimisation, and (b) explore the enantioselective mechanism. Assuming a 1:1 complex between each doxazosin enantiomer and CM‐β‐CD, studies of the relationship between the capacity factors (k′) and functions of CM‐β‐CD concentration indicate that the mechanisms for retention and chiral selectivity are comparable with those proposed earlier by Sybilska et al. 1 Stability constants (K G ) calculated for rac‐doxazosin complexed with CM‐β‐CD (647 ± 55 and 594 ± 45 M −1 for each enantiomer respectively) are significantly larger than those calculated for the barbiturates complexed with β‐CD (ca. 101–108 M −1 ). 1 Investigations on pH indicate an ionic or ion‐pair interaction between the anionic CM‐β‐CD and the cationic doxazosin enantiomers. A central composite design was used to optimise the key chromatographic parameters: pH, methanol (v/v) and CM/β‐CD concentration. The Kaiser peak separation index, P i , was used for the response function. The predicted response for this chiral separation has been compared with that observed experimentally and samples of the four‐dimensional response surface have been assessed for their value in showing robustness. Chirality 9:184–190, 1997. © 1997 Wiley‐Liss, Inc.