Development and validation of a cyclodextrin‐modified capillary electrophoresis method for the enantiomeric separation of vildagliptin enantiomers

Abstract

The enantiomers of vildagliptin, an orally available and selective dipeptidyl-peptidase-4 inhibitor used for the treatment of type II diabetes, have been separated by CD-modified CZE, using uncoated fused-silica capillary. After screening 13 negatively charged CD derivatives as potential chiral selectors, sulfobutyl-ether-α-CD (SBE-α-CD) was selected for the enantioseparation. For the optimization, a factorial analysis study was performed by orthogonal experimental design. Six experimental factors were chosen as variable parameters: temperature, applied voltage, chiral selector and BGE concentrations, pH, and the parameters of the hydrodynamic injection. The optimized system still was not considered final as the second peak (S-enantiomer) migrated too close to the EOF, resulting in a potential inaccuracy during the determination of the chiral impurity. To fine-tune the method "one factor at a time" variation approach was applied. The final method (applying 15°C capillary temperature, 40 mbar × 4 s hydrodynamic injection, 25 kV voltage in 75 mM acetate-Tris buffer [pH 4.75] containing 20 mM SBE-α-CD as chiral selector) was validated according to the ICH guideline. RSD percentage of the resolution value, migration times, and corrected peak areas were below 5% during testing repeatability and intermediate precision. LOD and LOQ values were found to be 2.5 and 7.5 μg/mL, respectively. The method is considered linear in the 7.5-180 μg/mL range for the R-enantiomer. The robustness of the method was justified using Plackett-Burmann statistical experimental design.

Validated capillary electrophoretic method for the enantiomeric quality control of R‐praziquantel

“…In the case of S‐β‐CD, interestingly, quasi‐equal complex stabilities were accompanied by extremely high enantioresolution values. The observed phenomena can be rationalized based on the large mobility difference of the transient diastereomeric complexes and the mechanism seems to be further proof that CE enantioseparation can be achieved based mostly on this mechanism .…”

“…Evaluation of robustness was performed according to the reports of Kazsoki et al. , varying the following experimental variables in a multivariate manner: capillary temperature (T; nominal value ± 2°C), applied voltage (U; ± 2 kV), CD concentration (c CD ; ± 2 mM), BGE concentration (c BGE ; ± 5 mM) and pH (± 0.1 pH units) . As response factors, migration times of S ‐PRZQ ( t 1 ) and R ‐PRZQ ( t 2 ), selectivity ( α ) and enantioresolution ( R s ) were recorded, as presented in Supporting Information Table S1.…”

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

“…Recently, sulfobutylether‐α‐CD (SBE‐α‐CD) was used in CE for the chiral separation of an inhibitor of the dipeptidyl‐peptidase‐4 enzyme, vildagliptin, and the method was applied for real sample analysis . In this study, 13 negatively charged CD derivatives were evaluated as possible CSs.…”

Simultaneous detection of zinc dimethyldithiocarbamate and zinc ethylenebisdithiocarbamate in cabbage leaves by capillary electrophoresis with inductively coupled plasma mass spectrometry

“…It is well known that Ziram and Zineb could not be easily separated by CZE without any treatment due to their neutrally charged property. In this study, the α-cyclodextrin, which was widely used for separation of chiral and achiral compounds [36][37][38][39][40][41][42][43][44][45][46][47][48], was chosen as the modifying agent to improve the resolution. The effect of α-cyclodextrin concentration on the separation of Ziram and Zineb was studied by adding different concentrations of α-cyclodextrin (5.0, 10.0, 15.0, 20.0, and 25.0 mmol/L) into running buffer solution (data not shown).…”