去甲万古霉素键合手性固定相拆分β-受体阻滞剂类药物及其结构类似物的研究  

Chiral Separation of β-Receptor Blockers and Analogs on Novel Norvancomycin-Bonded Chiral Stationary Phase

作　　者：丁国生[1] 刘莺[1] 丛润滋[1] 王俊德[1] 

机构地区：[1]中国科学院大连化学物理研究所,辽宁大连116012

出　　处：《色谱》2004年第4期386-389,共4页Chinese Journal of Chromatography

摘　　要：以去甲万古霉素为手性选择剂制备了大环抗生素类手性固定相去甲万古霉素键合手性固定相 (NVC CSP)。在极性有机模式下对普萘洛尔、美托洛尔、阿替洛尔及烯丙洛尔等 4种 β 受体阻滞剂类药物及其结构类似物的外消旋体进行了手性拆分的研究 ,并考察了流动相组成、酸碱添加剂用量、温度以及流速对分离的影响。研究发现 :在此模式下手性物质的保留均随着流动相中甲醇含量的增加而减弱 ,手性分离因子 (α)随着流动相中甲醇含量的增加而升高 ;随着柱温的升高 ,大部分溶质在色谱柱上的保留减弱 ,α值降低 ;在一定范围内降低流速有利于对映体的分离 ;对大部分的手性溶质来说 ,在流动相组成为乙腈 甲醇 乙酸 三乙胺 (6 0∶4 0∶0 4∶0 2 ,体积比 )、流速为 0 6mL/min、柱温为 2 5℃的条件下可获得最好的分离。研究结果表明 ,在极性有机模式下 ,π π电荷转移作用和偶极叠加作用参与了手性识别过程 ;氢键作用虽然会强烈影响手性物质的保留 ,但对手性分离不起主要作用。Enantiomeric separation of racemates of 8 β-receptor blockers and analogs was performed on a novel norvancomycin-bonded chiral stationary phase (NVC-CSP) in polar organic mode using high performance liquid chromatography. The influences of mobile phase composition, acetic acid and triethylamine contents, temperature and flow rate on enantiomeric separation were studied. It was found experimentally that with the increase of the fraction of methanol in the mobile phase, the same tendency was found for all the chiral solutes studied, i.e., the decrease in retention factor (k) and the increase in the enantioselectivity factor (α). With the increase of column temperature, most solutes were less retained and the α value decreased accordingly. Better resolutions were obtained at lower flow rates as a result of the minimization of the resistance to mass-transfer. Better separation results and suitable retentions for most solutes were obtained when a mixture of acetonitrile-methanol-acetic acid-triethylamine (60∶40∶0.4∶0.2, v/v) was used as mobile phase at a flow rate of 0.6 (mL/min), and the column temperature was set at 25 ℃. Conclusions can be drawn from the experimental data that π-π complexation, dipole-stacking interactions were engaged in the process of enantiomeric separation, while hydrogen bonding interaction between solutes and CSP was commonly non-enantioselective, although it was mainly responsible for the increased retention in the acetonitrile-predominant mobile phases.

关 键 词：高效液相色谱 去甲万古霉素 手性固定相 Β-受体阻滞剂 药物 

分 类 号：O658[理学—分析化学]