Study On Enantioseparation Of Amlodipine By Immobilized Chiral Ionic Liquids

Amlodipine is a powerful third-generation dihydropyridine calcium channel antagonist,which has the advantage of moderate reaction,stable hypotension and long-term safety and is recommended as the first-line antihypertensive drug by the World Health Organization for clinical antihypertensive treatment.However,when amlodipine racemic compounds were used in treatment in vitro in rat aortic evaluation,S-amlodipine is 1000 times more potent than R-amlodipine,while R-amlodipine may cause the release of nitric oxide in peripheral blood vessels and lead to peripheral hematoma.Two enantiomers and their salts have different pharmacological properties.Therefore,it is important to obtain a single S-amlodipine enantiomer in order to use it safely and effectively.Chiral ionic liquid(CIL)is a chiral selective agent with unique chiral recognition ability.There are many researches about CIL on extraction and separation,while its application in industry is limited by its high viscosity,difficult heat and mass transfer,high cost,difficult recovery and degradation.In order to overcome the defects of chiral ionic liquid in the extraction process,the separation of amlodipine enantiomers was studied by immobilized chiral ionic liquid on the substrate.The main contents are summarized as follows:1.A novel L-glutamate based immobilized chiral ionic liquid was prepared by chemical bonding method to recycle the chiral amino ionic liquid.The influence of substrate type,reaction solvent and alkalization time on the load amount of ionic liquid was studied,and the product was characterized by infrared spectroscopy,solid nuclear magnetism,thermogravimetric analysis,X-ray diffraction,etc.2.The performance of prepared immobilized ionic liquid was investigated for the absorption of S-amlodipine.The effects of adsorption time,initial concentration of S-amlodipine,pH value of solution and temperature on adsorption amount were investigated,and the experimental data was correlated by kinetic adsorption model and isotherm adsorption model.3.In order to investigate the separation effect of immobilized ionic liquid on amlodipine enantiomers,the immobilized ionic liquid was used to fill the glass chromatographic column.The influences of conditions such as sample concentration,sample volume,eluent composition,elution velocity,etc on the separation characteristic of solid phase extraction(SPE)was investigated.4.Amlodipine enantiomers were separated by liquid-liquid-solid extraction.The immobilized imidazolidyl 1-glutamic acid ionic liquid was used as the solid phase chiral selector,the amlodipine aqueous solution was the water phase,and organic solvent was the oil phase.The influence of oil phase types,dosage of extractant,amlodipine concentration and extraction temperature on the resolution of amlodipine were investigated.