Application Of CE In The Chiral Separation Of Drugs And Study On Mechanism Of Action

The pharmacological activity of chiral drugs is closely related to its stereo configuration.Determination of drug enantiomers by capillary electrophoresis(CE)is one of the key research directions in the field of pharmaceutical analysis.In this paper,ofloxacin and three amino acid enantiomers were separated by dual chiral selectors capillary electrophoresis,and the chiral separation mechanism was discussed by UV spectroscopy and nuclear magnetic resonance spectroscopy.In addition,a polydopamine/?-cyclodextrin capillary electrochromatography open tubular column was prepared by coating polymer stationary phase method,and the performance of the open tubular column was investigated.1.Determination ofloxacin enantiomers by CE method using a dual chiral selectors system and its study on the mechanismIn this chapter,the chiral separation of the ofloxacin enantiomers was studied using the dual chiral selector CE.Under the optimized conditions of 5 mmol/L sodium dihydrogen phosphate(8mg/mL carboxymethyl-?-cyclodextrin,8 mmol/L Cu(?),the molar ratio of Cu(?)and L-histidine is 1:1.3,pH 5.0),separation voltage is 15 kV,the resolution of the ofloxacin enantiomer is 2.24,and the analysis time is within 10 min.The mechanism of chiral separation was studied by UV spectroscopy,which indicated that carboxymethyl-?-cyclodextrin had synergistic effect with Cu(?)-L-histidine.In addition,the method was applied to the determination of the optical content of S-(-)-ofloxacin preparation,and the content of R-(+)-ofloxacin in S-(-)-ofloxacin eye drops and S-(-)-ofloxacin hydrochloride tablets was less than 0.1%.2.Determination amino acid enantiomers by CE method using a dual chiral selectors system and its study on the mechanismIn this chapter,the chiral separation of three amino acid enantiomers(D,L-tryptophan,D,L-tyrosine and D,L-phenylalanine)was studied using the dual chiral selector CE.Under the conditions of 5 mmol/L sodium dihydrogen phosphate(8 mmol/L ?-cyclodextrin,10 mmol/L Cu(?),the molar ratio of Cu(?)and L-histidine is 1:1.3,pH 5.0),separation voltage is 15 kV,the enantiomers of the three amino acids reached baseline separation,and the resolutions were 6.27,3.88 and 2.75,respectively.The composition of ?-cyclodextrin,Cu(?)-L-histidine and amino acid enantiomer in the separation system was studied by UV spectroscopy.It was proved that the presence of ?-cyclodextrin affected the complex composition of Cu(?)-L-histidine and amino acid enantiomer.The mechanism of chiral separation by nuclear magnetic resonance spectroscopy was further explored,indicating that ?-cyclodextrin and Cu(?)-L-histidine have synergistic effects on the separation of amino acid enantiomers.3.Preparation and application of capillary electrochromatography open tubular columnmodified by polydopamine-embedded ?-cyclodextrinIn this chapter,a polydopamine/?-cyclodextrin coated capillary electrochromatography open tubular column was prepared by coating a polymer stationary phase,and the coating conditions were determined: the coating solution was 10 mg/mL ?-cyclodextrin and 5 mg/mL dopamine,10mmol/L Tris-HCl(pH 8.5)was used as a solvent;after 30 min of coating,it was allowed to stand for 12 h.The capillary electrochromatography open tubular column was characterized by electroosmotic flow,scanning electron microscopy and infrared spectroscopy.The open tubular column was applied to the chiral separation of the tyrosine enantiomer by capillary electrochromatography.