去甲万古霉素键合毛细管电色谱硅胶整体柱的制备及应用

采用溶胶-凝胶技术制备了具有高机械强度和良好通透性的毛细管硅胶整体柱。以国产大环抗生素去甲万古霉素为 手性选择试剂对所制备的整体柱进行化学衍生,成功地制备了去甲万古霉素键合手性硅胶整体柱。在反相和极性有机相模 式下考察了所制备柱的手性识别能力,并详细考察了流动相条件对分离的影响。研究结果表明,β-受体阻滞剂类药物在极 性有机流动相组成为甲醇-乙腈-乙酸-三乙胺(体积比为80∶20∶0.1∶0.1)时,可获得最佳分离。在反相色谱条件下,电 渗流仍主要由整体硅胶基质材料产生,而手性选择试剂的贡献甚小。在反相色谱条件下,多种不同结构类型的手性药物在 所制备的色谱柱上获得了分离。

Preparation of Norvancomycin-Bonded Chiral Silica Monolithic Column for Capillary Electrochromatography and Its Applications

Silica-based monolithic column with high rigidity and good permeability was prepared by a modified sol-gel technology, characterized by shorter fabrication process and higher success rate. A macrocyclic antibiotics-based chiral monolithic column was successfully prepared by modifying the monolithic matrix with a homemade macrocyclic antibiotics--norvancomycin by adopting a single-step on-column derivatization process. The newly synthesized column was assessed for its enantioselectivity in chromatographic modes of reversed-phase and polar organic-phase. The effect of the mobile phase composition on the retention and enantioselectivity of the system was also investigated in detail. It was shown that beta-receptor blockers can be best resolved under the mobile phase composition of methanol-acetonitrile-triethyl-amine-acetic acid (80: 20: 0.1 : 0.1, v/v). Under reversed-phase conditions, a nearly linear increase of electroosmotic flow (EOF) was observed with the pH changing from 4.0 to 7.0, which shows that the predominant source of EOF is still resulting from the silica backbone while the chiral selector of norvancomycin contributes little. A number of racemic pharmaceuticals with different structures were separated in reversed-phase mode with different resolutions. It was shown experimentally that the column prepared in this way had broader enantioselectivity as well as better batch-to-batch reproducibility.