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

Abstract

The effect of ten water-soluble organic solvents on MEKC separation of palonosetron hydrochloride (PALO) stereoisomers using sodium cholate (SC) as chiral selector has been studied. The first chiral CE method fit for the analysis of unwanted PALO distomers (enantiomeric impurities) of low concentrations in the presence of high concentration of the main eutomer has been developed, based on solvent-modified MEKC mode. It was found that methanol provides the best separation among the solvents tested. And an SC concentration of 30 mM is proper to provide good resolutions in shorter time and adequate sample capacity, instead of 70 mM as previously reported. The developed method can be used to analyze unwanted PALO distomers of a few micrograms per milliliter in the presence of the main eutomer with a concentration as high as 1.0 mg/mL.

Recent advances in capillary electrophoretic migration techniques for pharmaceutical analysis (2013–2015)

“…The separation of all four stereoisomers was achieved by addition of methanol to a 30 mM sodium borate buffer, pH 9.20. Although the method was somewhat less sensitive as judged from the LODs of the minor isomers of 0.3 μg/mL as compared to the previous study , the solvent‐modified assay also allowed the precise quantitation of minor stereoisomers .…”

“…Several successful applications of CE for stereoisomeric purity testing have been reported and discussed . Table summarizes recent examples for the determination of the stereoisomeric purity of drug substances . Although not always calculated, LODs of 0.1 % or below were typically obtained.…”

“…This is due to the commercial availability of a wide variety of derivatives. Two studies employing different types of chiral selectors were published, i.e., the enantioseparation of amlodipine in the presence of maltodextrin and the separation of the stereoisomers of palonosetron by sodium cholate . The latter studies are also the only example of a chiral separation within the reviewed period of time using MEKC for the analysis of the stereochemical purity of a drug.…”

“…The method was subsequently validated with LODs of the minor enantiomers of 0.1 μg/mL . Subsequently, a solvent‐modified method was developed also using sodium cholate as chiral micelle‐forming agent . The separation of all four stereoisomers was achieved by addition of methanol to a 30 mM sodium borate buffer, pH 9.20.…”

The effects of organic modifier on physicochemical and chromatographic characteristics of self‐assembled micelle from poly (stearyl methacrylate‐co‐methacrylic acid) in electrokinetic chromatography

“…Just like in reversed phase HPLC, methanol, acetonitrile, tetrahydrofuran and isopropanol have also been used as the eluents to improve selectivity and peak shape . Furthermore, adding an organic solvents into the running electrolyte solution would increase the migration time window , which would benefit the resolution and peak capacity . These above‐mentioned organic solvents are referred to as Class II modifiers, which mainly change the running buffer properties such as polarity, dielectric constant, viscosity, etc.…”