| As the second and fourth generation of supramolecular host compounds, cyclodextrin and cucurbit[n]urils have a promising application prospect in the fields of catalysts, biochemistry, medicine, separating materials and sewage treatment, due to their good inclusion properties. In recent years, the inclusion of cucurbit[n]urils with drug molecules become a hot research, also become an important and effective means of new analytical methods for certain drugs to be established. A simple, accurate, reliable, sensitive, and repeatable analytical method of drugs is an effective way to control the drugs quality. The analytical method of drugs to be established is one of the main task of the analyst. Cyclodextrin has a wide range of applications in pharmaceutical analysis, which also has a broader application as materials for drug separation, especially chiral separation materials. Through depth study of the past20years, bridged cyclodextrin showed good characteristics in molecular recognition and molecular self-assembly, but has little application in chiral separation materials. In view of these essential characteristics above, the following aspects are researched in this paper:In the first part of this paper, research progress of cucurbit[n]urils in the fields of molecular recognition, molecular assembly, molecular device was summarized. The progress of cyclodextrin as chiral stationary phase, the chief characteristics and research results of bridged cyclodextrin were summarized in brief. Main contents of research in this paper was proposed.The second chapter describes a validated, simple, and sensitive fluorescence quenching method for the determination of ranitidine, nizatidine, and cimetidine in tablets and biological fluids. This is the first single fluorescence method reported for the analysis of all three H2antagonists. The competitive reaction between the investigated drug and the palmatine probe for the occupancy of the cucurbit[7]uril (CB[7]) cavity was studied using spectrofluorometry. CB[7] was found to react with the probe to form a stable complex. The fluorescence intensity of the complex was also enhanced greatly. However, the addition of the drug dramatically quenched the fluorescence intensity of the complex. Accordingly, a new fluorescence quenching method for the determination of the studied drugs was established. The different experimental parameters affecting the fluorescence quenching intensity were studied carefully. At optimum reaction conditions, the rectilinear calibration graphs between the fluorescence quenching values (ΔF) and the medicament concentration were obtained in the concentration range of0.04-1.9μg mL-1for the investigated drugs. The limits of detection ranged from0.013to0.030μg mL-1at495nm using an excitation wavelength of343nm. The proposed method can be used for the determination of the three H2antagonists in raw materials, dosage forms and biological fluids.The third chapter describes a simple and sensitive high performance liquid chromatography-fluorescence detector (HPLC-FLD) method which was developed for simultaneous determination of palmatine (PAL) and berberine (BRH). The method is based on the enhancement of the fluorescence of PAL and BRH in aqueous solution in the presence of cucurbit[7]uril (CB[7]). The chromatographic resolution of PAL and BRH was performed on SymmetryShieldTM RP18column with CB[7] as the mobile phase additive. The composition of the mobile phase was (50/50, v/v) absolute methanol/0.05%(v/v) triethylammonium acetate buffer (pH4.1) with1.25×10-4M CB[7]. The linear ranges of PAL and BRH were3-230and2-220ng mL-1, with the regression equations ofY-594248+7.56x104×(R=0.9993),Y=811028+6.32×104×(R=0.9995), respectively. The limits of detection for PAL and BRH were1and0.7ng·mL-1, respectively, with fluorescence detection at an excitation wavelength of347nm and an emission wavelength of495nm. The sensitivity of the proposed method was almost equal to previous liquid chromatography-mass spectroscopy method. The proposed method was applied to determine PAL and BRH in human plasma and Jinji capsules. The HPLC-FLD method was sensitive, and convenient.In the fourth chapter, a novel perhydroxyl-cucurbit[7]uril bonded stationary phase was prepared and used to separated protoberberine alkaloids (coptisine, berberine and jatrorrhizine) and opium alkaloids (narceine, codeine, thebaine, and monoacetylmorphine) by high-performance liquid chromatography (HPLC). The influence of mobile phase variation such as acetonitrile content, buffer concentration and pH to the chromatographic behavior was studied. The results showed that perhydroxyl-cucurbit[7]uril stationary phase had better selectivity for these protoberberine alkaloids than perhydroxyl-cucurbit[6]uril stationary phase and these opium alkaloids were obtained baseline separation in the two columns.In the fifth chapter, three diamino-bridged bis(β-cyclodextrin)s, namely1,3-(aminomethyl)-benzylamine-bridged bis(6-amino-6-deoxy-β-cyclodextrin)(1),4,4-diaminodiphenyl methano-bridged bis(6-amino-6-deoxy-β-cyclodextrin)(2), and4,4-ethylenedianiline-bridged bis(6-amino-6-deoxy-β-cyclodextrin)(3), were prepared and used in the novel application as chiral stationary phases (CSPs) in HPLC. Their ability to separate11enantiomers was investigated using triethylammonium acetate buffer containing methanol as the mobile phase. All three CSPs, particularly CSP1, have better enantiomer separation efficiencies than the parent β-cyclodextrin. Therefore, the linker length between two cyclodextrin units is effective to enantioselectivity, and the resolution ability decreases with increased linker length, which conforms with the molecular recognition ability.The sixth chapter describes a novel application of functionalized single-walled carbon nanotubes (SWCNTs) as a stationary phase for the liquid chromatographic separation of polycyclic aromatic hydrocarbons and structurally similar analogues. The SWCNTs were first oxidized to give carboxylic derivatives (SWCNT-COOH), afterwards these were covalently derivatized with hydroxypropyl-β-cyclodextrin (HP-β-CD). Then, the HP-β-CD-SWCNTs were bonded to silica gel with3-(triethoxysilyl) propyl isocyanate, which were used as a stationary phase to separate the investigated substances by HPLC. Eight polycyclic aromatic hydrocarbons were separated using water/methanol(5:5, v/v) as the mobile phase, and six structurally similar dipine drugs were separated using (3:7, v/v) methanol/triethylammonium acetate buffer (0.1%, v/v, pH4.1) as the mobile phase on this stationary phase. The results showed that the HP-β-CD-SWCNTs stationary phase had stronger separation ability for aromatic hydrocarbons and analogues compared with the HP-β-CD stationary phase. This method can be used to improve the separation efficiency of the β-CD stationary phases.The chief characteristics and innovations of this thesis are as follows:1. Cucurbit[7]uril was used for the determination of three H2antagonists ranitidine, nizatidine and cimetidine. Therefore, the three H2antagonists which have no fluorescence can be determined by fluoremetry. The fluoremetry is more sensitive than the normal spectroscopic method, so can be used to determine the three H2antagonists in biological fluids.2. A simple and sensitive high performance liquid chromatography-fluorescence detector (HPLC-FLD) method was developed for simultaneous determination of palmatine (PAL) and berberine (BRH) using CB[7] as the mobile phase additive. The method was more sensitive than the normal chromatographic method, almost equal to expensive liquid chromatography-mass spectroscopy method. The proposed method can be applied to determine PAL and BRH in biological fluids. The above HPLC-FLD method was sensitive and convenient.3. Several novel chromatography stationary phases were prepared and their respective separation advantages were also evaluated. Perhydroxyl-cucurbit[7]uril bonded stationary phase have certain advantages in separating alkaloids drugs. Diamino-bridged bis(β-cyclodextrin)s with short bridged group had better enantiomer separation efficiencies than the parent β-cyclodextrin. Single-walled carbon nanotubes (SWCNTs) alone used in the stationary phase had poor separation effect. However, SWCNTs, derivatized with hydroxypropyl-β-cyclodextrin (HP-β-CD) as a stationary phase showed good separative capability of environmental pollutants polycyclic aromatic hydrocarbons and structurally similar analogues. SWCNTs had certain potential application in the improvement of the separation efficiency of the β-CD stationary phases. |
PDF Full Text Request