Fast separation of warfarin and 7‐hydroxywarfarin enantiomers by cyclodextrin‐assisted capillary electrophoresis

Abstract

The enantioseparation of warfarin and its main metabolite has been achieved using several cyclodextrin types and buffers at different pH, including conditions that have not been attempted so far. Methyl-β-cyclodextrin, highly sulfated-β-cyclodextrin and highly sulfated-γ-cyclodextrin were the most efficient chiral selectors. The pH range, within which particular cyclodextrins support chiral separation, has been approximately determined for the first time. By shortening the effective capillary length to 10 cm, the time of analysis has been vastly reduced <2 min. Hence, baseline separations of warfarin and 7-hydroxywarfarin enantiomers have been achieved in times unreported for those species until now. The established conditions are promising for the further development of new highly selective and fast methods involving warfarin, its derivatives, as well as the same cyclodextrin types.

Chiral Separations by Capillary Electrophoresis and related Techniques with Different Chiral Selectors: A Review

“…Given the wide application of alkaline drugs, sulfated modifiednegatively charged CDs have become the most commonly used chiral selector, since it has obvious advantages in chiral separations. This can occur with the onset of new electrical interaction and ion exchange interaction, which can enable them to demonstrate improved enantiorecognition capacity [142,[179][180][181][182][183][184][185]. For example, the potential of Chondroitin sulfate D and Chondroitin sulfate E, two representatives of the glycosaminoglycans group, to be evaluated as chiral selectors, was tested for the first time in CE.…”

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

“…Nowak et al. examined the chiral separation of warfarin and 7‐hydroxywarfarin by using native‐α‐ and β‐CD, HP‐β‐CD, methyl‐β‐CD (M‐β‐CD), and negatively charged CDs as CSs in CE. Two modes of injection (long‐ and short‐end injection) were utilized.…”

“…S‐β‐CD, highly sulfated β‐CD (HS‐β‐CD) and highly sulfated‐γ‐CD (HS‐γ‐CD) have also been used for the separation of different drug and pharmaceutical compounds. S‐β‐CD was used for the chiral separation of 4‐chloromethcathione , phenylpropanolamine and chlorpheniramine , while HS‐γ‐CD was able to separate both enantiomeric pairs of warfarin and 7‐hydroxywarfarin . In addition, Thormann and his research group utilized HS‐γ‐CD in order to perform kinetic studies for ketamine and its metabolites .…”

Capillary electrophoretic enantioseparation of basic drugs using a new single-isomer cyclodextrin derivative and theoretical study of the chiral recognition mechanism

“…Most of separations of chiral compounds in CE were achieved by the addition of chiral selectors to the running buffer. To date, cyclodextrins (CDs) , antibiotics , polysaccharides and crown ethers , etc. have been used for the chiral separation of enantiomers by CE.…”