Enhancement of chiral drugs separation by a novel adjustable gravity mediated capillary electrophoresis combined with sulfonic propyl ether ß-CD polymer.

A water-soluble negative sulfonic propyl ether ß-CD polymer (SPE-ß-CDP) to be used as chiral selector in capillary electrophoresis (CE) was polymerized. The sulfonic substitution degree of each ß-CD in SPE-ß-CDP was statistically homogenized. The only one negative peak in electrophoretogram with indirect ultraviolate method proved its uniformity of electrophoretic behavior. There were 7.12 sulfonic substitution in ß-CD unit and 164 µmole ß-CD units in each gram of SPE-ß-CDP, which corresponded a molecular weight of 7000 or more. Compared with monomer, SPE-ß-CDP was lower effect on electrical current of CE, indicating a high concentration of SPE-ß-CDP could be added. Its separation ability was verified by 12 chiral drugs. SPE-ß-CDP also showed advantages of good water solubility, easy preparation and recovery to reduce the overall cost. However, five of 12 chiral drugs were hardly to be fully separated which was normal for any kind of chiral selector. A newly adjustable gravity mediated capillary electrophoresis (AGM-CE) technology was proposed and combined with SPE-ß-CDP to enhance the chiral separation efficiencies of propranolol, salbutamol, omeprazole, ofloxacin and phenoxybenzamine which were markedly improved to 3.02, 1.17, 7.63, 4.14, and 2.81, respectively. Furthermore, its gradient mode (AGMg-CE) was also used to improve resolution through utilizing the zero mobility point, at which the effective apparent mobility of one racemate was zero. Resolutions of five chiral drugs were significantly improved, especially resolution of carvedilol changed from 0.43 to 1.0. These indicated SPE-ß-CDP as chiral selector, AGM-CE and AGMg-CE as new CE technologies had a great potential in chiral separation.

Synthesis and applications of sulfopropyl ether γ-cyclodextrin polymer as chiral selector in capillary electrophoresis.

A novel sulfopropyl ether γ-cyclodextrin polymer (SPE-γ-CDP) through polycondensating sulfated cyclodextrins (SCDs) was synthesized. This synthesis approach also has the potential of preparing other derived cyclodextrins (CDs) polymers. The polymerized SCDs took on both the properties of SCDs and certain characteristics of polymers, such as chiral selectivity and high viscosity. Synthesis parameters, including reactions sequence, sulfation, and polycondensation conditions were investigated systematically. The product was characterized by elemental analysis, infrared spectroscopy (IR), and indirect UV detections prior to use as background electrolytes additive. The separation conditions, including the concentration of SPE-γ-CDP, the concentration and pH of running buffer, separation voltage, as well as the additional organic solution were optimized during chiral separation of neutral, acidic, and basic enantiomers in capillary electrophoresis (CE). SPE-γ-CDP was proven to be an effective chiral resolving agent in CE with the advantages of simple synthesis process, low cost, similar ratio of charge-to-mass, low current, great reproducibility, and reusability. Graphical Abstract Synthesis and applications of sulfopropyl ether γ-cyclodextrin polymer.