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用于外消旋药物直接对映体选择性反相纳米液相色谱分离的手性β-环糊精功能化聚合物整体柱

Chiral β-cyclodextrin functionalized polymer monolith for the direct enantioselective reversed phase nano liquid chromatographic separation of racemic pharmaceuticals.

作者信息

Ahmed Marwa, Ghanem Ashraf

机构信息

Chirality Program, Biomedical Science, University of Canberra, Canberra, Australian Capital Territory (ACT) 2601, Australia.

Chirality Program, Biomedical Science, University of Canberra, Canberra, Australian Capital Territory (ACT) 2601, Australia.

出版信息

J Chromatogr A. 2014 Jun 6;1345:115-27. doi: 10.1016/j.chroma.2014.04.023. Epub 2014 Apr 16.

Abstract

2,3,6-Tris(phenylcarbamoyl)-β-cyclodextrin-6-methacrylate was prepared and used as a functional monomer for the preparation of new β-cyclodextrin (β-CD) functionalized polymer monoliths. The polymer monoliths were prepared via the copolymerization of β-CD methacrylate and ethylene glycol dimethacrylate in different ratios in situ in fused silica capillary (internal diameter 150 μm). The effect of functional monomer/cross linker concentration on the chiral separation of different classes of pharmaceuticals namely; α- and β-blockers, antiinflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs and antiarrhythmic drugs was investigated. Baseline separation was achieved for propranolol, ifosfamide, alprenolol, tertalol, 1-indanol, tebuconazole, o-methoxymandelic acid, celiprolol and cizolertine under reversed phase conditions with mobile phase composed of methanol and water, using nano liquid chromatography. The method provides more economical analysis under environmentally benign conditions. The prepared capillary columns showed good mechanical stability and good repeatability (run-to run and batch-to batch).

摘要

制备了2,3,6-三(苯基氨基甲酰基)-β-环糊精-6-甲基丙烯酸酯,并将其用作制备新型β-环糊精(β-CD)功能化聚合物整体柱的功能单体。通过在熔融石英毛细管(内径150μm)中原位以不同比例使甲基丙烯酸β-CD与乙二醇二甲基丙烯酸酯共聚来制备聚合物整体柱。研究了功能单体/交联剂浓度对不同种类药物(即α-和β-阻滞剂、抗炎药、抗真菌药、多巴胺拮抗剂、去甲肾上腺素-多巴胺再摄取抑制剂、儿茶酚胺、镇静催眠药、利尿剂、抗组胺药、抗癌药和抗心律失常药)手性分离的影响。在反相条件下,使用由甲醇和水组成的流动相,通过纳米液相色谱法实现了普萘洛尔、异环磷酰胺、阿普洛尔、特他洛尔、1-茚醇、戊唑醇、邻甲氧基扁桃酸、塞利洛尔和西佐利定的基线分离。该方法在环境友好的条件下提供了更经济的分析。制备的毛细管柱显示出良好的机械稳定性和良好的重复性(运行间和批次间)。

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