Luo Rongying, Han Hai, Liu Jia, Xu Dongsheng, Wang Qiqin, Fanali Salvatore, Jiang Zhengjin
Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University, Guangzhou, 510632, China.
Institute of Pharmaceutical Analysis, College of Pharmacy, Jinan University, Guangzhou, 510632, China; International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Chinese Ministry of Education (MOE), College of Pharmacy, Jinan University, Guangzhou, 510632, China.
J Pharm Biomed Anal. 2020 Apr 15;182:113129. doi: 10.1016/j.jpba.2020.113129. Epub 2020 Jan 27.
A novel chiral stationary phase (CSP), based on a monolithic organic polymer chemically modified with teicoplanin, was fabricated within a 100 μm I.D. fused silica capillary. The teicoplanin was firstly derivatized with 2-isocyanatoethyl methacrylate (ICNEML) and then thermally co-polymerized with the crosslinker ethylene dimethacrylate (EDMA) in presence of porogens (methanol and dimethylsulfoxide). The optimal experimental conditions (e.g., concentration and ratio of the reagents), considering enantioresolution and permeability, were systematically investigated. The prepared monolith was evaluated using scanning electron microscopy, and the column exhibited quite good morphology. In order to further evaluate the enantioresolving power of the poly(ICNEML-teicoplanin-co-EDMA) monolith, a series of basic and acidic chiral compounds were analyzed using an isocratic mode of polar organic solvents (methanol and acetonitrile) or the same solvents in combination with water (reversed-phase) by nano-liquid chromatography. Five mandelic acids and six derivatized amino acids were enantioresolved under reversed-phase mode (R = 1.22-3.47 and α = 1.43-6.33). This monolithic teicoplanin-CSP was also effective in the enantioseparations of 17 amino alcohol drugs employing polar-organic phase mode (MeOH/ACN/TEA/HOAc (80/20/0.03/0.055, v/v/v/v)). Ten of them were baseline enantioresolved (alprenolol, betaxolol, clenbuterol, isoproterenol, metoprolol, pindolol, propranolol, salbutamol, sotalol, tertatolol) (R = 1.55-2.48 and α = 1.21-1.55), while the others were partially enantioseparated (R = 1.14-1.48).
一种基于用替考拉宁化学修饰的整体有机聚合物的新型手性固定相（CSP），被制备在内径为100μm的熔融石英毛细管内。替考拉宁首先用甲基丙烯酸2-异氰酸酯乙酯（ICNEML）进行衍生化，然后在致孔剂（甲醇和二甲基亚砜）存在下与交联剂二甲基丙烯酸乙烯酯（EDMA）进行热共聚。考虑到对映体拆分和渗透率，系统地研究了最佳实验条件（例如试剂的浓度和比例）。使用扫描电子显微镜对制备的整体柱进行了评估，该柱表现出相当好的形态。为了进一步评估聚（ICNEML-替考拉宁-共-EDMA）整体柱的对映体拆分能力，通过纳米液相色谱，使用极性有机溶剂（甲醇和乙腈）的等度模式或相同溶剂与水混合（反相），对一系列碱性和酸性手性化合物进行了分析。在反相模式下，五种扁桃酸和六种衍生化氨基酸实现了对映体拆分（R = 1.22 - 3.47，α = 1.43 - 6.33）。这种整体式替考拉宁-CSP在采用极性有机相模式（MeOH/ACN/TEA/HOAc（80/20/0.03/0.055，v/v/v/v））对17种氨基醇类药物的对映体分离中也有效。其中十种实现了基线对映体拆分（阿普洛尔、倍他洛尔、克仑特罗、异丙肾上腺素、美托洛尔、吲哚洛尔、普萘洛尔、沙丁胺醇、索他洛尔、特他洛尔）（R = 1.55 - 2.48，α = 1.21 - 1.55），而其他的则实现了部分对映体分离（R = 1.14 - 1.48）。
