| Nowadays, chiral drugs in international pharmaceutical market shares have been climing year after year. With the increasing demand for optical pure chiral drugs, establishing a rapid method for enantioseparation makes a significant contribution to study pharmacokinetic studies and product quality control. In this thesis, our object focused on the development a novel kind of chiral staionary phase, studied from two aspects including support materials and chiral selectors of CSPs to supply new enantioseparation materials for the establishing of rapid and efficient HPLC methods. Based on new research results of mesoporous materias in recent years, we synthesized mesoporous silica materials which were suitable for HPLC stationary phase, and then bonded with useful derived P-cyclodextrins ((3-CD). We expected to obtain novel CSPs with good performance for fast chiral analysis via fine combination ofβ-cyclodextrins and mesoporous materials. The products were characterized by Fourier transform infrared spectrometry(FTIR), X-ray diffraction (X-RD), scanning electron microscopy(SEM), elemental analysis and so on. The chromatographic performances of CSPs were evaluated, and related separation mechanisms were systematically studied. The major contents are as follows:(1) The recent study advances of chiral stationary phases and mesoporous materials at home and broad were reviewed including the aspects of enantioseparation meaning, classification of CSPs and their applications in chromatography separation. Among them, the developments ofβ-CD CSPs, ordered mesoporous materials and their chromatographic applications were reviewed, respectively. All above will contribute to the research basis of this thesis.(2) SBA-15 mesoporous silica materials had been synthesized using triblock copolymer poly(ethyleneoxide)-block-poly(propyleneoxide)-block-poly (ethyleneoxide) (P123) as structure directing agent and tetraethyl orthosilicate(TEOS) as silicon resource with the assistance of cetyltriethylammnonium bromide (CTAB); The perphenylcarbamoylatedβ-CD bonded SBA-15 chiral stationary phase was synthesized with Y-glycidoxy-propyltrimethoxy-silane (KH-560) as coupling reagent via a ring-opening reaction of epoxy. The main synthetic conditions were investigated, and the new stationary phase was characterized by FTIR, X-RD,SEM and elemental analysis. The chromatographic performane of a 5-cm short column packed with perphenylcarbamoylatedβ-CD bonded SBA-15 was demonstrated by enantioseparation of common fiveβ-blocker drugs including alprenolol, propranolol, mexiletine, metoprolol and pindolol in RP-HPLC. The results showed that the 5-cm short p-CD-based column exhibited rapid separation ability to the aboveβ-blocker drugs within 5 min, which indicated that the separation has high efficiency. According to the chemical structures of theβ-blockers and their chromatographic behavior, related separation mechanisms were also discussed.(3) A mesoporous SBA-15 silica materials with large pore has been synthesized using P123 as structure directing agent and TEOS as silicon resource and 1,3,5-trimethylbenzene (TMB) as pore-expanding reagent. Then (mono-6-ethylene diamine-6-deoxy-2,3,6-tert-butylisocyanated)-β-cyclodextrin ligand was immobilized onto the surface of above SBA-15 silica via 3-isocyanopropyl triethylsiloxane as coupling reagent under mild condition. After derivation reaction a tert-butylisocyanatedβ-CD bonded SBA-15 silica CSP was obtained. The extension of hydrophobic cavity ofβ-CD in the large pore of SBA-15 made the interaction between the analytes andβ-CD ligand stronger and effectively and provided better separation. The resulting product was characterized by related instrumental methods.11 basic chiral drugs were successfully separated on the new CSP column in RP-HPLC within 6 min, respectively. Some effects of composition, buffer concentration and pH value in mobile phase on the chiral selectivity ofβ-blockers were also investigated preliminarily, and the related chromatographic parameters were partially optimized. The results showed that the short CD-based 5-cm column also exhibited rapid separation ability to the above drugs within several minutes, which indicated that the SBA-15 separation materials with has highly potential in fast enantioseparation.(4) Firstly synthesizedβ-CD-mono-6-(N-aminoethyl)-3-aminopropyl trimethoxy silane(β-CD-siloxane). Follow that a novel mesoporous chiral materials withβ-CD in channels were directly prepared by usingβ-CD-siloxane with 1,2-bis(triethoxysilyl)-ethane (BTEE) as silica resources and CTAB as template in hydrothermal synthesis method. After phenylcarbamated with phenyl isocyanate an organo-inorganic chiral silica composite(β-CD PMO) was obtained, in whichβ-CD on the wall of channels and ethyl groups in the skeleton. The PMO as chiral stationary phase (CSP) was employed for enantioseparartion of some basic drugs containing nitrogen under different modes, such as RP-HPLC and NP-HPLC conditions. The results showed that theβ-CD PMO was successfully used to separate basic drugs with only common mobile phases at a similar pH value (pH 4.15). The maximum enantioseparartion selectivity factor (a) was 2.42. Additionally, excellent permeability and reproducibility facilitate the establishment of new enantioseparation method for chiral drugs. The chromatographic data indicated thatβ-CD PMO has advantage in chiral separartions of drugs. |
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