Analytical and Bioanalytical Chemistry

, Volume 409, Issue 30, pp 7087–7096 | Cite as

Selective extraction and determination of chlorogenic acids as combined quality markers in herbal medicines using molecularly imprinted polymers based on a mimic template

  • Wenhua Ji
  • Mingming Zhang
  • Huijiao Yan
  • Hengqiang Zhao
  • Yan Mu
  • Lanping Guo
  • Xiao WangEmail author
Research Paper


We describe a solid-phase extraction adsorbent based on molecularly imprinted polymers (MIPs), prepared with use of a mimic template. The MIPs were used for the selective extraction and determination of three chlorogenic acids as combined quality markers for Lonicera japonica and Lianhua qingwen granules. The morphologies and surface groups of the MIPs were assessed by scanning electron microscopy, Brunauer–Emmett–Teller surface area analysis, and Fourier transform infrared spectroscopy. The adsorption isotherms, kinetics, and selectivity of the MIPs were systematically compared with those of non-molecularly imprinted polymers. The MIPs showed high selectivity toward three structurally similar chlorogenic acids (chlorogenic acid, cryptochlorogenic acid, and neochlorogenic acid). A procedure using molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography was established for the determination of three chlorogenic acids from Lonicera japonica and Lianhua qingwen granules. The recoveries of the chlorogenic acids ranged from 93.1% to 101.4%. The limits of detection and limits of quantification for the three chlorogenic acids were 0.003 mg g−1 and 0.01 mg g−1, respectively. The newly developed method is thus a promising technique for the enrichment and determination of chlorogenic acids from herbal medicines.

Graphical Abstract

Mimic molecularly imprinted polymers for the selective extraction of chlorogenic acids.


Molecularly imprinted polymers Mimic template Solid-phase extraction Chlorogenic acid Lonicera japonica Thunb 



This research was supported by the National Natural Science Foundation of China (81473298, 81603286), the Key Science and Technology Program of Shandong (2014GSF119031), the Natural Science Foundation of Shandong (ZR2016YL006), the Shandong Province Taishan Scholar Program (Lanping Guo), and the Priority Research Program of the Shandong Academy of Sciences (Lanping Guo).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

216_2017_667_MOESM1_ESM.pdf (517 kb)
ESM 1 (PDF 517 kb)


  1. 1.
    Li SP, Zhao J, Yang B. Strategies for quality control of Chinese medicines. J Pharm Biomed Anal. 2011;55:802–9.CrossRefGoogle Scholar
  2. 2.
    Xie PS, Leung AY. Understanding the traditional aspect of Chinese medicine in order to achieve meaningful quality control of Chinese materia medica. J Chromatogr A. 2009;1216:1933–40.CrossRefGoogle Scholar
  3. 3.
    Yang Y, Wang HJ, Yang J, Brantner AH, Lower-Nedza AD, Si N, et al. Chemical profiling and quantification of Chinese medicinal formula Huang-Lian-Jie-Du decoction, a systematic quality control strategy using ultra high performance liquid chromatography combined with hybrid quadrupole-orbitrap and triple quadrupole mass spectrometers. J Chromatogr A. 2013;1321:88–9.CrossRefGoogle Scholar
  4. 4.
    Qi LW, Cao J, Li P, Wang YX. Rapid and sensitive quantitation of major constituents in Danggui Buxue Tang by ultra-fast HPLC–TOF/MS. J Pharm Biomed Anal. 2009;49:502–7.CrossRefGoogle Scholar
  5. 5.
    Shi Z, Song D, Li R, Yang H, Qi L, Xin G, et al. Identification of effective combinatorial markers for quality standardization of herbal medicines. J Chromatogr A. 2014;1345:78–85.CrossRefGoogle Scholar
  6. 6.
    Nakamura T, Nakazawa Y, Onizuka S. Antimutagenicity of Tochu tea (an aqueous extract of Eucommia ulmoides leaves): 1. The clastogen-suppressing effects of Tochu tea in CHO cells and mice. Mutat Res. 1997;338:7–20.CrossRefGoogle Scholar
  7. 7.
    Chen L, Wang X, Lu W, Wu X, Li J. Molecular imprinting: perspectives and applications. Chem Soc Rev. 2016;45:2137–211.CrossRefGoogle Scholar
  8. 8.
    Miranda LFC, Domingues DS, Queiroz MEC. Selective solid-phase extraction using molecularly imprinted polymers for analysis of venlafaxine, O-desmethylvenlafaxine, and N-desmethylvenlafaxine in plasma samples by liquid chromatography–tandem mass spectrometry. J Chromatogr A. 2016;1458:46–53.CrossRefGoogle Scholar
  9. 9.
    Cao J, Yan H, Shen S, Bai L, Liu H, Qiao F. Hydrophilic molecularly imprinted melamine-urea-formaldehyde monolithic resin prepared in water for selective recognition of plant growth regulators. Anal Chim Acta. 2016;943:136–45.CrossRefGoogle Scholar
  10. 10.
    Ji W, Zhang M, Wang T, Wang X, Zheng Z, Gong J. Molecularly imprinted solid-phase extraction method based on SH-Au modified silica gel for the detection of three Sudan dyes in chili powder samples. Talanta. 2017;165:18–26.CrossRefGoogle Scholar
  11. 11.
    Hernández-Mesa M, Cruces-Blanco C, García-Campaña AM. Capillary electrophoresis-tandem mass spectrometry combined with molecularly imprinted solid phase extraction as useful tool for the monitoring of 5-nitroimidazoles and their metabolites in urine samples. Talanta. 2017;163:111–20.CrossRefGoogle Scholar
  12. 12.
    Zhao T, Guan X, Tang W, Ma Y, Zhang H. Preparation of temperature sensitive molecularly imprinted polymer for solid-phase microextraction coatings on stainless steel fiber to measure ofloxacin. Anal Chim Acta. 2015;853:668–75.CrossRefGoogle Scholar
  13. 13.
    Urraca JL, Chamorro-Mendiluce R, Orellana G, Moreno-Bondi MC. Molecularly imprinted polymer beads for clean-up and preconcentration of β-lactamase-resistant penicillins in milk. Anal Bioanal Chem. 2016;408:1843–54.CrossRefGoogle Scholar
  14. 14.
    Pichon V, Combès A. Selective tools for the solid-phase extraction of ochratoxin A from various complex samples: immunosorbents, oligosorbents, and molecularly imprinted polymers. Anal Bioanal Chem. 2016;408:6983–99.CrossRefGoogle Scholar
  15. 15.
    Hu Y, Pan J, Zhang K, Lian H, Li G. Novel applications of molecularly-imprinted polymers in sample preparation. Trends Anal Chem. 2013;43:37–52.CrossRefGoogle Scholar
  16. 16.
    Gu X, Xu R, Yuan G, Lu H, Gu B, Xie H. Preparation of chlorogenic acid surface-imprinted magnetic nanoparticles and their usage in separation of traditional Chinese medicine. Anal Chim Acta. 2010;675:64–70.CrossRefGoogle Scholar
  17. 17.
    Golsefidi MA, Es’haghi Z, Sarafraz-Yazdi A. Design, synthesis and evaluation of a molecularly imprinted polymer for hollow fiber-solid phase microextraction of chlorogenic acid in medicinal plants. J Chromatogr A. 2012;1229:24–9.CrossRefGoogle Scholar
  18. 18.
    Liu Q, Zhao Y, Pan J, Bruggen B, Shen J. A novel chitosan base molecularly imprinted membrane for selective separation of chlorogenic acid. Sep Purif Technol. 2016;164:70–80.CrossRefGoogle Scholar
  19. 19.
    Li H, Li G, Li Z, Lu C, Li Y, Tan X. Surface imprinting on nano-TiO2 as sacrificial material for the preparation of hollow chlorogenic acid imprinted polymer and its recognition behavior. Appl Surf Sci. 2013;264:644–52.CrossRefGoogle Scholar
  20. 20.
    Li H, Liu Y, Zhang Z, Liao H, Nie L, Yao S. Separation and purification of chlorogenic acid by molecularly imprinted polymer monolithic stationary phase. J Chromatogr A. 2005;1098:66–74.CrossRefGoogle Scholar
  21. 21.
    Miura C, Matsunaga H, Haginaka J. Molecularly imprinted polymer for caffeic acid by precipitation polymerization and its application to extraction of caffeic acid and chlorogenic acid from Eucommia ulmodies leaves. J Pharm Biomed Anal. 2016;127:32–8.CrossRefGoogle Scholar
  22. 22.
    Miura C, Li H, Matsunaga H, Haginaka J. Molecularly imprinted polymer for chlorogenic acid by modified precipitation polymerization and its application to extraction of chlorogenic acid from Eucommia ulmodies leaves. J Pharm Biomed Anal. 2015;114:139–44.CrossRefGoogle Scholar
  23. 23.
    Sun X, Wang J, Li Y, Jin J, Yang J, Li F, et al. Highly class-selective solid-phase extraction of bisphenols in milk, sediment and human urine samples using well-designed dummy molecularly imprinted polymers. J Chromatogr A. 2014;1360:9–16.CrossRefGoogle Scholar
  24. 24.
    You QP, Peng MJ, Zhang YP, Guo JF, Shi SY. Preparation of magnetic dummy molecularly imprinted polymers for selective extraction and analysis of salicylic acid in Actinidia chinensis. Anal Bioanal Chem. 2014;406:831–9.CrossRefGoogle Scholar
  25. 25.
    Zhu F, Wang J, Zhu L, Tan L, Feng G, Liu S, et al. Preparation of molecularly imprinted polymers using theanine as dummy template and its application as SPE sorbent for the determination of eighteen amino acids in tobacco. Talanta. 2016;150:388–98.CrossRefGoogle Scholar
  26. 26.
    Liu R, Feng F, Chen G, Liu Z, Xu Z. Barbell-shaped stir bar sorptive extraction using dummy template molecularly imprinted polymer coatings for analysis of bisphenol A in water. Anal Bioanal Chem. 2016;408:5329–35.CrossRefGoogle Scholar
  27. 27.
    Wang XH, Zhang J, Peng C, Dong Q, Huang YP, Liu ZS. Comparison of multi-recognition molecularly imprinted polymers for recognition of melamine, cyromazine, triamterene, and trimethoprim. Anal Bioanal Chem. 2015;407:7145–55.CrossRefGoogle Scholar
  28. 28.
    Mei XQ, He XP, Wang JT. Molecularly imprinted polymer as efficient sorbent of solid-phase extraction for determination of gonyautoxin 1,4 in seawater followed by high-performance liquid chromatography-fluorescence detection. Anal Bioanal Chem. 2016;408:5737–43.CrossRefGoogle Scholar
  29. 29.
    Lian Z, Li HB, Wang J. Experimental and computational studies on molecularly imprinted solid-phase extraction for gonyautoxins 2,3 from dinoflagellate Alexandrium minutum. Anal Bioanal Chem. 2016;408:5527–35.CrossRefGoogle Scholar
  30. 30.
    Wulandari M, Urraca JL, Descalzo AB, Amran MB, Moreno-Bondi MC. Molecularly imprinted polymers for cleanup and selective extraction of curcuminoids in medicinal herbal extracts. Anal Bioanal Chem. 2015;407:803–12.CrossRefGoogle Scholar
  31. 31.
    Wang M, Chang X, Wu X, Yan H, Qiao F. Water-compatible dummy molecularly imprinted resin prepared in aqueous solution for green miniaturized solid-phase extraction of plant growth regulators. J Chromatogr A. 2016;1458:9–17.CrossRefGoogle Scholar
  32. 32.
    Lenain P, Mavungu JDD, Dubruel P, Robbens J, Saeger SD. Development of suspension polymerized molecularly imprinted beads with metergoline as template and application in a solid-phase extraction procedure toward ergot alkaloids. Anal Chem. 2012;84:10411–8.CrossRefGoogle Scholar
  33. 33.
    Van Uitert LG, Haas CG. Studies on coördination compounds. I. A method for determining thermodynamic equilibrium constants in mixed solvents. J Am Chem Soc. 1953;75:451–5.CrossRefGoogle Scholar
  34. 34.
    Wang Y, Wang Y, Ouyang X, Yang L. Surface-imprinted magnetic carboxylated cellulose nanocrystals for the highly selective extraction of three fluoroquinolones from egg samples. ACS Appl Mater Interfaces. 2017;9:1759–69.CrossRefGoogle Scholar
  35. 35.
    Ji W, Sun R, Duan W, Wang X, Wang T, Mu Y, et al. Selective solid phase extraction of chloroacetamide herbicides from environmental water samples by amphiphilic magnetic molecularly imprinted polymers. Talanta. 2017;170:111–8.CrossRefGoogle Scholar
  36. 36.
    Ji W, Wang T, Liu W, Liu F, Guo L, Geng Y, et al. Water-compatible micron-sized monodisperse molecularly imprinted beads for selective extraction of five iridoid glycosides from Cornus officinalis fructus. J Chromatogr A. 2017;1504:1–8.CrossRefGoogle Scholar
  37. 37.
    Xu X, Duhoranimana E, Zhang X. Preparation and characterization of magnetic molecularly imprinted polymers for the extraction of hexamethylenetetramine in milk samples. Talanta. 2017;163:31–8.CrossRefGoogle Scholar
  38. 38.
    Saad EM, Madbouly A, Ayoub N, Nashar RME. Preparation and application of molecularly imprinted polymer for isolation of chicoric acid from Chicorium intybus L. medicinal plant. Anal Chim Acta. 2015;877:80–9.CrossRefGoogle Scholar
  39. 39.
    Li N, Ng TB, Wong JH, Qiao JX, Zhang YN, Zhou R, et al. Separation and purification of the antioxidant compounds, caffeic acid phenethyl ester and caffeic acid from mushrooms by molecularly imprinted polymer. Food Chem. 2013;139:1161–7.CrossRefGoogle Scholar
  40. 40.
    Pardo A, Mespouille L, Dubois P, Blankert B, Duez P. Molecularly imprinted polymers : compromise between flexibility and rigidity for improving capture of template analogues. Chem Eur J. 2014;20:3500–9.CrossRefGoogle Scholar
  41. 41.
    Chinese Pharmacopoeia Commission. Chinese pharmacopoeia. Vol. I. People’s Medical Publishing House: Beijing, 2010; p 205−206.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Wenhua Ji
    • 1
  • Mingming Zhang
    • 2
  • Huijiao Yan
    • 1
  • Hengqiang Zhao
    • 1
  • Yan Mu
    • 1
  • Lanping Guo
    • 3
  • Xiao Wang
    • 1
    Email author
  1. 1.Shandong Key Laboratory of TCM Quality Control Technology, Shandong Analysis and Test CenterShandong Academy of SciencesJinanChina
  2. 2.School of Life SciencesShandong Normal UniversityJinanChina
  3. 3.Resource Center of Chinese Materia Medica, State Key Laboratory Breeding Base of Dao-di HerbsChina Academy of Chinese Medical SciencesBeijingChina

Personalised recommendations