Study On Preparation Of The Chiral Drug Extraction Split And Imprinted Monolithic Column

Enantioseparation of MA,Phe,naproxen were investigated using co-extraction,aqueous two-phase extraction,molecular imprinting technique.(1) The distribution behavior of MA enantiomers was examined in a two-phase aqueous-organic solvent mixture containing D2EHPA and tartaric acid derivatives as co-extractants.The influence of tartaric acid derivative's species and its initial concentration,the initial concentration of D2EHPA,D,L-MA and extractive equilibrium temperature on the distribution ratio and enantioselectivity were studied.The results showed that both the distribution ratio and enantioselectivity were greatly improved by using D2EHPA and tartaric acid derivatives as co-extractants in comparison with that using tartaric acid derivatives individually;the co-extractants of D2EHPA and D-tartaric acid derivatives formed more stable diastereomeric complexs with L-MA than with D-MA;the enantioselectivity of D2EHPA and DTTA co-extractants were better than D2EHPA and DBTA co-extractants;The influence of the intial concentration of D,L-MA and the extractive equilibrium temperature on the distribution ratio and enantioselectivity were insignificant.The thermodynamic studies on enantiomer separation of MA by chiral extraction indicated that the enantiomeric separation is an enthalpy-controlled process.(2) The distribution behavior of MA enantiomers was investigated in aqueous two-phase systems composing of polyethylene glycol and ammonium sulfate containingβ-cyclodextrin as chiral selector.The influences of the pH,the mass fraction of polyethylene glycol and ammonium sulfate,the polymerization degree of polyethylene glycol,the initial concentration ofβ-cyclodextrin,MA enantiomers and extractive temperature on the distribution behavior were studied,respectively.The results showed thatβ-cyclodextrin is inclined to recognize L-enantiomer; under the optimized conditions,the enantioselectivity reaches 2.46. Aqueous two-phase chiral extraction is of strong chiral separation ability, plays a great role in preparative separation of racemic compounds and is important for the development of aqueous two phase extraction technique.(3) The distribution behavior of Phe enantiomers was investigated in aqueous two-phase systems composing of polyethylene glycol and ammonium sulfate containing combinatproal chiral selector:β-CD and HP-β-CD in order to establish the optima chiral extraction conditions in this experiment.The influences of the molar concentration ratios of combinatorial chiral selectors,the total molar concentration of combinatorial chiral selectors,pH values,buffer type and its concentraction were investigated.The results showed that the enantioselectivity reaches 1.53 under the optima chiral extraction conditions.(4) An naproxen molecularly imprinted monolithic column was prepared by in situ polymerization using AM as a functional monomer, EGDMA as a cross-linking agent,toluene and dodecanol as porogenic solvents,and AIBN as an initiator.The synthesis condition was optimized. The results showed the best ratio of template to functional monomer was 1:4,the crosslinker content in monomer mixture was 85%and the toluene content in porogen was 20%.Some chromatographic conditions such as the acetic acid concentration in mobile phase,the flow rate and temperature were characterized.The separation factor reached 2.13 under conditions of the temperature of 60℃,the flow rate of 0.6mL/min and the volume ratio of 99.9:0.1 between acetonitrile and acetic acid in mobile phase.