摘要
手性药物的对映体理化性质极其相似,而药理、毒理作用常常存在显著差异,因此探索提高对映体分离性能的创新策略对手性分离具有重要意义。以往关于毛细管电泳(CE)中β-受体阻断药美托洛尔(MET)对映体分离的研究主要集中在仅添加手性选择剂环糊精(CD)及其衍生物,而对于在CD的基础上添加辅助添加剂的研究较少。本研究将3种深共晶溶剂(DESs)氯化胆碱-葡萄糖、氯化胆碱-果糖和乳酸-葡萄糖作为辅助添加剂,用于MET的CE手性分离,推测了DES对基于CD的毛细管电泳分离MET对映体的协同作用。首先考察了CD种类、CD浓度、缓冲液pH值和缓冲液浓度对MET分离的影响,优化得到了最优条件(15 mmol/L羧甲基-β-环糊精、pH=3.0、40 mmol/L磷酸盐缓冲液)。其次制备了3种DESs作为添加剂,研究不同DESs及其质量分数对手性分离的作用,最终确定了最佳条件:采用质量分数1.5%的氯化胆碱-果糖型DES,此时MET的分离度从不添加DES时的1.30提升至2.61,实现了基线分离。最后对分离效果以及机理进行了推测。本文所建立的MET对映体手性分离分析方法不仅对提高手性药物质量、保证临床用药安全有效具有重要意义,还有助于将DES协同用于CD衍生物毛细管电泳手性分离的进一步研究与发展。
The physical and chemical properties of chiral drugs are very similar.However,their pharmacological and toxicological effects vary significantly.For example,one enantiomer may have favorable properties whereas the other may be ineffective or even have toxic side effects.Hence,exploring innovative strategies to improve enantiomeric resolution is of great importance.Metoprolol(MET)is aβ-receptor blocker used to treat hypertension,stable angina pectoris,and supraventricular tachyarrhythmia.Establishing chiral separation and analysis methods of MET enantiomers is important for enhancing the quality of chiral drugs.Capillary electrophoresis(CE)has the advantages of a small sample size,simple operation,high separation efficiency,and many alternative modes;therefore it is widely used in the field of chiral drug separation.The chiral selectors commonly used for CE-based chiral separation include cyclodextrin(CD)and its derivatives,polysaccharides,proteins,and macrocyclic antibiotics.CD is one of the most commonly used and effective chiral selectors for CE.The relatively hydrophobic structure inside the cavity and the relatively hydrophilic structure outside the cavity of CD enable[HJ56x]it and chiral molecules to form inclusion compounds with different binding constants,thus achieving chiral separation.However,the use of CD alone as a chiral selector does not always yield satisfactory separation results.Hence,the addition of other additives,such as ionic liquids and deep eutectic solvents(DESs)to assist CD-based chiral separation systems has received extensive attention.Previous studies on the enantiomeric separation of MET by CE have focused on the addition of CD and its derivatives alone for separation.Few studies have been conducted on the synergistic addition of auxiliary additives to CD to improve the enantiomeric resolution of MET.In this study,three DESs,namely,choline chloride-D-glucose,choline chloride-D-fructose,and lactate-D-glucose,were used for the CE-based chiral separation of MET for the first time,and th
作者
李小倩
夏之宁
LI Xiaoqian;XIA Zhining(School of Pharmacy,Chongqing University,Chongqing 401331,China)
出处
《色谱》
CAS
CSCD
北大核心
2024年第4期327-332,共6页
Chinese Journal of Chromatography
基金
国家自然科学基金(21974015).
关键词
毛细管电泳
协同作用
手性分离
深共晶溶剂
美托洛尔
capillary electrophoresis(CE)
synergistic interaction
chiral separation
deep eutectic solvents(DESs)
metoprolol(MET)
