| Sulfobutylether-?-cyclodextrin(SBE-?-CD),is a negatively charged derivative of ?-CD,compare with ?-CD,which possesses an extended hydrophobic cavity and an extremely hydrophilic exterior surface.Furthermore,SBE-?-CD,in terms of the advantages of higher aqueous solubility and safety,less renal toxicity,has been employed as a welcome pharmaceutical excipient for various poorly soluble drugs to enhance their solubility and bioavailabilities.The formation of inclusion complex between SBE-?-CD and small molecule drug is of great interest in the fields of chemistry and pharmacy.In this work,using flow injection-chemiluminescence(FI-CL)analysis,based on the CL of luminol/SBE-?-CD,by the homemade model of interaction between SBE-?-CD and small drug molecules,lg[(Io-Is)/Is]= 1gk + nlg[C],the interaction of SBE-?-CD and sedative hypnotic drugs was investigated.The interaction parameters(formation constant K,stoichiometric ratio n)and thermodynamic parameters(?H,?S,?G)were given.Based on the relationship between the CL intensity of luminol/SBE-?-CD system and the concentrations of drugs,the analytical method for the determination of drugs was established,and the proposed method was successfully applied to the determination of trace drugs in different spiked and real samples(including human serum,urine,pharmaceutical capsules and tablets).The content of this thesis included two parts,as follows:Part 1 ReviewChapter 1 Introduction105 references were cited.The current development of researching technologies of interaction of SBE-?-CD and small molecules(especially drugs)was reviewed;the application of SBE-?-CD and the research methods of SBE-?-CD and small molecules were introduced;and the CL system of luminol/SBE-?-CD was also given;the significance and contents of this dissertation were given.Part 2 Application of Luminol/SBE-?-CD chemiluminescence systemChapter 2:Study on the interaction of SBE-?-CD with sedative hypnotic drugsBy homemade FI-CL model of SBE-P-CD and small molecules interaction,the interaction parameters(K:103?107 L mol-1,n:approximately 1.0)of SBE-?-CD and sedative hypnotic drugs were obtained at different temperatures,suggested that SBE-?-CD and sedative hypnotic drugs may form a 1:1 complex on line;Furthermore,it was found that the values of K followed the order of MEP<SEC<CZP<PPH,and the variation of K was related to the structure and hydrophobicity of drugs.Thermodynamic parameters(?H:14.15?142.78 kJ mol-1,?S:112.73?662.28 J mol L-1,?G:-42.66?-19.44 kJ mol-1)revealed the main stable force for the spontaneously formed complexes of SBE-?-CD and sedative hypnotic drugs was hydrophobic interaction;the interaction mode of SBE-?-CD/sedative hypnotic drugs was also investigated by molecule docking(Autodock 4.2)and the result revealed sedative hypnotic drugs entered into the larger cavity of SBE-?-CD with hydrogen bonds,the values of AG,K well agreeing with the experimental datas by FI-CL.Chapter 3:Determination of PPH by Luminol/SBE-?-CD systemBased on the linear relationship of the decrement of luminol/SBE-?-CD/PPH CL intensity against the logarithm of PPH concentration,the FI-CL method for the determination of PPH at picogram levels was established,with the linear range from 0.03 to 30.0 ng mL-1 and the limit of detection(LOD)0.01 ng mL-1(3?).The proposed procedure was successfully applied to PPH determination in biological fluids and tablets with recoveries from 94.5 to 105.6%and RSDs less than 2.6%(n = 5).This work has been published in the journal of Bulletin of the Korean Chemical Soceity,2013,Vol.34,No.11,pp3199-3205.Chapter 4:Determination of CZP by Luminol/SBE-?-CD systemBased on the good linear relationship of CL intensity decrement against the logarithm of CZP concentration within 0.07?50.0 ng mL-1,a FI-CL method with the detection limit of 0.02 ng mL-1(3?)for CZP quantification was established for the first time.The proposed CL method was successfully applied to the determination of CZP in spiked human urine and serum samples,with recoveries from 92.1 to 108.2%and the relative standard deviations(RSDs)less than 2.7%(n = 7).This work has been published in the journal of Instrumentation Science and Technology,2014,Vol.42,ppl-13.Chapter 5:Study of CRD pharmacokineticsBased on CRD quenching effect on luminol/SBE-?-CD CL system,determination of CRD was established by FI-CL method.The proposed CL method was successfully applied to the determination of CRD in CRD capsules,with recoveries from 93.7 to 105.8%and the relative standard deviations(RSDs)less than 2.5%(n = 7);human urine in 8 h after a single oral intake of 500 mg were continuously monitored,with recoveries of 90.0%?106.8%(RSDs<3.4%,n= 7).The pharmacokinetic parameters for CRD(ka:0.670±0.008 h-1,ke:0.744 ± 0.005 h-1,t1/2:0.93 ± 0.05 h)were successfully obtained. |
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