Enantioseparation of basic drugs by reverse phase high‐performance liquid chromatography system using carboxymethyl‐β‐cyclodextrin as chiral mobile phase additive

Abstract

A rapid and efficient method was developed for enantioseparation of basic drugs, using carboxymethyl‐β‐cyclodextrin (CM‐β‐CD) as chiral mobile phase additive, rather than involving costly chiral column in high‐performance liquid chromatography (HPLC) system. Four of the six basic drug enantiomers investigated were successfully separated. The highest resolution reaches 2.15 for threo‐(1S,2S)‐2‐amino‐l‐p‐nitrophenyl‐1,3‐propanediol. The effects of the organic modifier, pH value, concentration of chiral additive, column temperature, and flow rate of mobile phase on the enantioseparation of analytes were researched. The apparent formation constants of inclusion and the thermodynamic parameters were evaluated to explain the mechanism of chiral recognition.

Recent Advances in Separation and Analysis of Chiral Compounds

“…Chiral mobile-phase additive can avoid the utilization of a costly chiral column to develop efficient enantio-separation methods. For example, 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and carboxy methyl-β-cyclodextrin (CM-β-CD) served as mobile-phase additives for baseline separation of mandelic acid derivatives and basic drug enantiomers on achiral C18 HPLC column, respectively. , More CD derivative-based composites were fabricated as CSPs for chiral HPLC. Compared with the additive of 2,6-di-O-methyl-β-CD, the CSP of 2,6-di-O-methyl-β-CD gave better HPLC enantio-separation performance for four phenethylamine enantiomers, indicating the greater efficiency of CSP in chiral HPLC .…”

Synthesis by carbonate aminolysis and chiral recognition ability of cellulose 2,3-bis(3,5-dimethylphenyl carbamate)-6-(α-phenylethyl carbamate) selectors

“…Nowadays, mostly chiral stationary phases in high-performance liquid chromatography (HPLC) are used for the direct separation of pairs of enantiomers and other stereoisomers -both on an analytical and a preparative scale (Ahuja 1997;Subramanian 2008). Another separation approach is the use of chiral (enantiopure) mobile phase additives for the formation of transient diastereomeric species in HPLC -besides other indirect approaches, such as derivatization with chiral species and subsequent separation of the resulting diastereomers (Peng et al 2016;Yu et al 2019;Ao et al 2022;Chen et al 2022;Bao et al 2022). Chiral/asymmetric synthesis (Xue et al 2018;Wojaczyńska and Wojaczyński 2020;Qian et al 2021;Zhu et al 2021;Sun et al 2022) and the kinetic resolution of enantiomers (Musa 2020;Spelmezan et al 2020;Harwood et al 2021; Huang racemic compounds or enantiomeric mixtures (Ikai and Okamoto 2009;Shen and Okamoto 2016;Yin et al 2019a).…”

New methods for resolution of hydroxychloroquine by forming diastereomeric salt and adding chiral mobile phase agent on RP‐HPLC

“…Compared to the former methods, RP‐HPLC with the addition of CMPA represents a more convenient and cost‐effective method. Building on prior investigations, CM‐β‐CD and sulfobutylether‐β‐cyclodextrin (SBE‐β‐CD) have been found to be highly effective in the HPLC resolution of chiral bases 27,28 . However, according to our preliminary experiments, SBE‐β‐CD proved to be ineffective for the enantio‐separation of HCQ.…”

“…Building on prior investigations, CM-β-CD and sulfobutylether-β-cyclodextrin (SBE-β-CD) have been found to be highly effective in the HPLC resolution of chiral bases. 27,28 However, according to our preliminary experiments, SBE-β-CD proved to be ineffective for the enantio-separation of HCQ.…”