Analytical and Bioanalytical Chemistry

, Volume 409, Issue 1, pp 201–211 | Cite as

Enhancement of selective separation on molecularly imprinted monolith by molecular crowding agent

  • Xian-Hua WangEmail author
  • Qian Dong
  • Ling-Ling Ying
  • Shuai-Shuai Chi
  • Yao-Han Lan
  • Yan-Ping Huang
  • Zhao-Sheng LiuEmail author
Research Paper


In this study, a new molecularly imprinted polymer chiral stationary phase (MIP-CSP) was prepared utilizing molecular crowding agent for improvement the selective separation ability. S-amlodipine (S-AML), methacrylic acid (MAA), ethylene glycol dimethacrylate (EDMA), and polymethyl methacrylate (PMMA) were selected as template, functional monomer, cross-linker, and molecular crowding agent, respectively. The composition of formulas for MIP-CSP was optimized, and the permeability and structural feature of resultant MIP-CSP were characterized. The effect of mobile-phase composition, including ionic strength, pH, and organic modifier content, was investigated for achieving the selective separation of rac-amlodipine (rac-AML) on MIP-CSP. The baseline separation of rac-AML was achieved with resolution of 1.58, whereas no selective separation was observed on the imprinted monolith without molecular crowding agent. The perturbation chromatography method was successfully applied to evaluate the recognition mechanism of templates on MIP-CSP. The retention time of S-AML detected in typical analytical conditions was obviously greater than the time of negative peak derived from perturbation, which indicated the retention of template may be due to the imprinted cavities on MIP-CSP. Additionally, the result of Van’t Hoff analysis indicated that the chiral separation of rac-AML on MIP-CSP was an entropy-driven process, which supported the molecular imprinting theory. These results reveal that molecular crowding is a potential strategy for preparation of MIP-CSP with excellent selective separation ability.

Graphical Abstract

Improvement of chiral separation on molecularly imprinted monolith by molecular crowding condition


Molecularly imprinting Molecular crowding Separation Monolith Perturbation chromatography 



This work was supported by the National Natural Science Foundation of China (grant no. U1303202), Tianjin Natural Science Foundation (grant no. 16JCQNJC05500), and the Hundreds Talents Program of the Chinese Academy of Science.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

216_2016_9986_MOESM1_ESM.pdf (619 kb)
ESM 1 (PDF 618 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Xian-Hua Wang
    • 1
    Email author
  • Qian Dong
    • 1
  • Ling-Ling Ying
    • 1
  • Shuai-Shuai Chi
    • 1
  • Yao-Han Lan
    • 1
  • Yan-Ping Huang
    • 1
  • Zhao-Sheng Liu
    • 1
    Email author
  1. 1.Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics (Theranostics), School of PharmacyTianjin Medical UniversityTianjinChina

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