Separation mechanisms for palonosetron stereoisomers at different chiral selector concentrations in MEKC

Abstract

The separation mechanisms for palonosetron (PALO) stereoisomers in MEKC using sodium cholate (SC) as surfactant and chiral selector have been studied, in a wide range of concentrations below and above the CMC. It was found that SC micelles only provide chirally selective recognition for 3a carbon chiral center in PALO molecules. The resolution of the configurations of 2 carbon chiral center is achieved by the difference of mobility in continuous phase. A schematic diagram depicting the separation mechanisms and the corresponding migration orders among all of four stereoisomers was proposed based on the measured separation parameters. A MEKC method to achieve the complete separation of four stereoisomers in very short time using a very low chiral selector concentration, instead of high concentrations generally considered, was developed based on the understanding of the mechanisms.

Solvent‐modified MEKC for the enantioseparation of palonosetron hydrochloride and related enantiomeric impurities

“…Both the increase and decrease in pH from this value deteriorate the separation between diastereoisomers PALO (3aR, 2R) and (3aS, 2R). This may be ascribed to the biggest mobility difference between two enantiomeric pairs at pH 9.20 (Supporting Information Table 1), which dominates the separation between PALO (3aR, 2R) and (3aS, 2R), according to our previous research on separation mechanisms [14,15]. In our explanation, the pKa of two pairs of PALO enantiomers (protonated) have little difference and this pH is close to the pKa, so it gives rise to the biggest difference in ionization degree and thus the biggest mobility difference a) Migration time of the EOF represented by DMSO.…”

“…And the run time was too long (33 min) to meet the requirement of routine analysis. We have also developed chiral EKC methods to achieve the baseline resolution of all the four PALO stereoisomers with SC chiral selector . In these studies, the main focus was on the fundamental principles such as separation mechanisms and elution orders, thus method validations were not carried out yet.…”

Bile Salts in Chiral Micellar Electrokinetic Chromatography: 2000–2020

“…In the study by Tian and co-workers, the chiral separation of palonosetron hydrochloride enantiomers was affected by sodium cholate [ 37 ]. Meanwhile, Hu and co-workers investigated the separation mechanism of the same drug at varying sodium cholate concentrations [ 34 ], while Guo and co-workers introduced a thermodynamic model to elucidate the migration order of palonosetron hydrochloride enantiomers [ 38 ]. In another study, Trapp used sodium cholate with the probe ferroin (tris(1,10-phenanthroline)-Fe(II)) complex to investigate the effect of temperature and Joule heating in MEKC [ 39 ].…”

“…This concentration was observed to be the CMC of the primary micelle in aqueous solution. Interestingly, independent research from Hu and co-workers using palonosetron hydrochloride as an analyte probe arrived at 10 mM as the primary CMC of sodium cholate [ 34 ]. However, there was an observable degradation in chiral resolution in high sodium cholate concentrations (≥30 mM).…”

Chiral selectors in CE: Recent development and applications (mid‐2014 to mid‐2016)

“…In another study, the chiral separation of palonosetron, which has two chiral centers, and its separation mechanism were investigated by using sodium cholate as a CS in MEKC . Separation of the diastereomers was achieved when sodium cholate was used at concentrations ≤ 10 mM.…”