Analytical and Bioanalytical Chemistry

, Volume 410, Issue 2, pp 373–389 | Cite as

Dummy-surface molecularly imprinted polymers as a sorbent of micro-solid-phase extraction combined with dispersive liquid–liquid microextraction for determination of five 2-phenylpropionic acid NSAIDs in aquatic environmental samples

  • Ping Guo
  • Xucan Yuan
  • Jingjing Zhang
  • Binjie Wang
  • Xiaoyang Sun
  • Xiaohui ChenEmail author
  • Longshan ZhaoEmail author
Research Paper


A highly binding dummy template surface of molecularly imprinted polymers (MWNTs-MIPs) was synthesized on multi-walled carbon nanotubes surface using 2-phenylpropionic acid as dummy template, 4-vinylpyridine as the functional monomer, ethylene glycol dimethacrylate as the cross-linker, and DMF as porogen by precipitation polymerization method. MIPs were characterized by FT-IR spectroscopy, scanning electron microscope, thermo-gravimetric analysis, and nitrogen adsorption-desorption experiment. Adsorption and selectivity experiments of MIPs and non-imprinted polymers (NIPs) verified that the MIPs had a good selectivity and adsorption properties for five 2-phenylpropionic acid nonsteroidal anti-inflammatory drugs (NSAIDs). Imprinted polymer was used as a sorbent material for μSPE in current work and μSPE-DLLME method was selected for pretreatment of water samples. The μSPE-DLLME method was successfully used for the pre-concentration of five non-steroidal anti-inflammatory drugs in different environmental water samples prior to ultra-high performance liquid chromatography-tandem mass spectrometry. Efficiencies of μSPE and DLLME were thoroughly investigated and optimized in this study. The optimal results were obtained by using 3 mL of 1% formic acid-acetonitrile as elution solvent and dichloroethane and acetonitrile as extractant and disperser solvent, respectively. Limits of detection and quantification of five NSAIDs for different water matrices varied from 0.50 to 1.10 ng L−1 and 0.93 to 2.20 ng L−1, respectively. Each target analyte had a good linearity in its corresponding concentration range. Enrichment factors of target analytes ranged from 91 to 215. Recoveries of the target analytes were between 72.43 and 113.99% at the concentration levels of 0.02, 0.1, and 0.5 μg L−1. The developed method was successfully applied to extraction and analysis of NSAIDs in different water samples with satisfactory results which could help us better understand their environmental fate and risk to ecological health.

Graphical abstract

Dummy-surface molecularly imprinted polymers as a sorbent of micro-solid-phase extraction combined with dispersive liquid–liquid microextraction for determination of five 2-phenylpropionic acid NSAIDs in aquatic environmental samples


Surface molecular imprinted polymer Dummy template Multi-walled carbon nanotubes Environmental samples μSPE-DLLME 



This work was supported by the National Natural Science Foundation of China (No. 81503029) and Yong and Middle-aged Backbone Personnel Training Program of Shenyang Pharmaceutical University (ZQN2016011).

Compliance with ethical standards

Conflict of interest

The authors have declared no conflict of interest. The authors alone are responsible for the content and writing of this article.


  1. 1.
    Annamalai J, Namasivayam V. Endocrine disrupting chemicals in the atmosphere: their effects on humans and wildlife. Environ Int. 2015;76:78–97.CrossRefGoogle Scholar
  2. 2.
    Guo C-C, Tang Y-H, Hu H-H, Yu L-S, Jiang H-D, Zeng S. Analysis of chiral non-steroidal anti-inflammatory drugs flurbiprofen, ketoprofen and etodolac binding with HSA. Chinese J Anal Chem. 2011;1(3):184–90.Google Scholar
  3. 3.
    Kosjek T, Heath E, Krbavčič A. Determination of non-steroidal anti-inflammatory drug (NSAIDs) residues in water samples. Environ Int. 2005;31(5):679–85.CrossRefGoogle Scholar
  4. 4.
    Puckowski A, Mioduszewska K, Łukaszewicz P, Borecka M, Caban M, Maszkowska J, et al. Bioaccumulation and analytics of pharmaceutical residues in the environment: a review. J Pharmaceut Biomed. 2016;127:232–55.CrossRefGoogle Scholar
  5. 5.
    SanJuan-Reyes N, Gomez-Olivan LM, Galar-Martinez M, Garcia-Medina S, Islas-Flores H, Gonzalez-Gonzalez ED, et al. NSAID-manufacturing plant effluent induces geno- and cytotoxicity in common carp (Cyprinus carpio). Sci Total Environ. 2015;530-531:1–10.CrossRefGoogle Scholar
  6. 6.
    Mezzelani M, Gorbi S, Da RZ, Fattorini D, D'Errico G, Milan M, et al. Ecotoxicological potential of non-steroidal anti-inflammatory drugs (NSAIDs) in marine organisms: bioavailability, biomarkers and natural occurrence in Mytilus galloprovincialis. Mar Environ Res. 2016;121:31.CrossRefGoogle Scholar
  7. 7.
    Schwaiger J, Ferling H, Mallow U, Wintermayr H, Negele RD. Toxic effects of the non-steroidal anti-inflammatory drug diclofenac. Part I: histopathological alterations and bioaccumulation in rainbow trout. Aquat Toxicol. 2004;68(2):141–50.CrossRefGoogle Scholar
  8. 8.
    Lin WC, Chen HC, Ding WH. Determination of pharmaceutical residues in waters by solid-phase extraction and large-volume on-line derivatization with gas chromatography-mass spectrometry. J Chromatogr A. 2005;1065(1065):279–85.CrossRefGoogle Scholar
  9. 9.
    Rezaee M, Assadi Y, Milani Hosseini M-R, Aghaee E, Ahmadi F, Berijani S. Determination of organic compounds in water using dispersive liquid–liquid microextraction. J Chromatogr A. 2006;1116(1–2):1–9.CrossRefGoogle Scholar
  10. 10.
    Boonchiangma S, Ngeontae W, Srijaranai S. Determination of six pyrethroid insecticides in fruit juice samples using dispersive liquid-liquid microextraction combined with high performance liquid chromatography. Talanta. 2012;88:209–15.CrossRefGoogle Scholar
  11. 11.
    Moreira BJ, Borges KB, de Oliveira ARM, de Gaitani CM. Analysis of oxybutynin and N-desethyloxybutynin in human urine by dispersive liquid–liquid microextraction (DLLME) and capillary electrophoresis (CE). Anal Methods. 2015;7(20):8763–70.CrossRefGoogle Scholar
  12. 12.
    Stolker AAM, Rutgers P, Oosterink E, Lasaroms JJP, Peters RJB, van Rhijn JA, et al. Comprehensive screening and quantification of veterinary drugs in milk using UPLC–ToF-MS. Anal Bioanal Chem. 2008;391(6):2309–22.CrossRefGoogle Scholar
  13. 13.
    Fan H, Yao Q. Development of new solid phase extraction techniques in the last ten years. Chinese J Anal Chem. 2013;22(4):293–302.Google Scholar
  14. 14.
    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
  15. 15.
    Song YP, Li N, Zhang HC, Wang GN, Liu JX, Liu J, et al. Dummy template molecularly imprinted polymer for solid phase extraction of phenothiazines in meat based on computational simulation. Food Chem. 2017;233:422–8.CrossRefGoogle Scholar
  16. 16.
    Feng MX, Wang GN, Yang K, Liu HZ, Wang JP. Molecularly imprinted polymer-high performance liquid chromatography for the determination of tetracycline drugs in animal derived foods. Food Control. 2016;69:171–6.CrossRefGoogle Scholar
  17. 17.
    Qiang M. Yuan-Yuan, Jiao, Chong, Jing, Chun, Chang, Jian. Separation and enrichment of trace ractopamine in biological samples by uniformly-sized molecularly imprinted polymers. Chinese J Anal Chem. 2012;2(6):395–402.Google Scholar
  18. 18.
    Byun HS, Youn YN, Yun YH, Yoon SD. Selective separation of aspirin using molecularly imprinted polymers. Sep Purif Technol. 2010;74(1):144–53.CrossRefGoogle Scholar
  19. 19.
    Madikizela LM, Chimuka L. Determination of ibuprofen, naproxen and diclofenac in aqueous samples using a multi-template molecularly imprinted polymer as selective adsorbent for solid-phase extraction. J Pharmaceut Biomed. 2016;128:210.CrossRefGoogle Scholar
  20. 20.
    Ning F, Qiu T, Wang Q, Peng H, Li Y, Wu X, et al. Dummy-surface molecularly imprinted polymers on magnetic graphene oxide for rapid and selective quantification of acrylamide in heat-processed (including fried) foods. Food Chem. 2017;221:1797–804.CrossRefGoogle Scholar
  21. 21.
    Chen L, Xu S, Li J. Recent advances in molecular imprinting technology: current status, challenges and highlighted applications. Chem Soc Rev. 2011;40(5):2922–42.CrossRefGoogle Scholar
  22. 22.
    Hu JH, Feng T, Li WL, Zhai H, Liu Y, Wang LY, et al. Surface molecularly imprinted polymers with synthetic dummy template for simultaneously selective recognition of nine phthalate esters. J Chromatogr A. 2014;1330:6–13.CrossRefGoogle Scholar
  23. 23.
    Ning F, Qiu T, Wang Q, Peng H, Li Y, Wu X, et al. Dummy-surface molecularly imprinted polymers on magnetic graphene oxide for rapid and selective quantification of acrylamide in heat-processed (including fried) foods. Food Chem. 2016;221:1797.CrossRefGoogle Scholar
  24. 24.
    Hu JH, Feng T, Li WL, Zhai H, Liu Y, Wang LY, et al. Surface molecularly imprinted polymers with synthetic dummy template for simultaneously selective recognition of nine phthalate esters. J Chromatogr A. 2014;1330(8):6–13.CrossRefGoogle Scholar
  25. 25.
    He X, Chen J, Wang J, Tan L. Multipoint recognition of domoic acid from seawater by dummy template molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography. J Chromatogr A. 2017;1500:61–8.CrossRefGoogle Scholar
  26. 26.
    Liang N, Huang P, Hou X, Li Z, Tao L, Zhao L. Solid-phase extraction in combination with dispersive liquid-liquid microextraction and ultra-high performance liquid chromatography-tandem mass spectrometry analysis: the ultra-trace determination of 10 antibiotics in water samples. Anal Bioanal Chem. 2016;408(6):1701–13.CrossRefGoogle Scholar
  27. 27.
    Yi PS, Nan L, Hui CZ, Geng NW, Ju XL, Jing L, et al. Dummy template molecularly imprinted polymer for solid phase extraction of phenothiazines in meat based on computational simulation. Food Chem. 2017;233:422.CrossRefGoogle Scholar
  28. 28.
    Xi S, Kai Z, Xiao D, Hua H. Computational-aided design of magnetic ultra-thin dummy molecularly imprinted polymer for selective extraction and determination of morphine from urine by high-performance liquid chromatography. J Chromatogr A. 2016;1473:1–9.CrossRefGoogle Scholar
  29. 29.
    Arabi M, Ghaedi M, Ostovan A. Development of dummy molecularly imprinted based on functionalized silica nanoparticles for determination of acrylamide in processed food by matrix solid phase dispersion. Food Chem. 2016;210:78–84.CrossRefGoogle Scholar
  30. 30.
    Xu H, Schönhoff M, Zhang X. Unconventional layer-by-layer assembly: surface molecular imprinting and its applications. Small. 2012;8(4):517–23.CrossRefGoogle Scholar
  31. 31.
    Safdarian M, Ramezani Z, Ghadiri AA. Facile synthesis of magnetic molecularly imprinted polymer: Perphenazine template and its application in urine and plasma analysis. J Chromatogr A. 2016;1455:28–36.CrossRefGoogle Scholar
  32. 32.
    Ma RT, Shi YP. Magnetic molecularly imprinted polymer for the selective extraction of quercetagetin from Calendula officinalis extract. Talanta. 2015;134:650–6.CrossRefGoogle Scholar
  33. 33.
    Hu X, Wu X, Yang F, Wang Q, He C, Liu S. Novel surface dummy molecularly imprinted silica as sorbent for solid-phase extraction of bisphenol A from water samples. Talanta. 2016;148:29–36.CrossRefGoogle Scholar
  34. 34.
    Yang X, Zhang Z, Li J, Chen X, Zhang M, Luo L, et al. Novel molecularly imprinted polymers with carbon nanotube as matrix for selective solid-phase extraction of emodin from kiwi fruit root. Food Chem. 2014;145:687–93.CrossRefGoogle Scholar
  35. 35.
    Rao W, Cai R, Yin Y, Long F, Zhang Z. Magnetic dummy molecularly imprinted polymers based on multi-walled carbon nanotubes for rapid selective solid-phase extraction of 4-nonylphenol in aqueous samples. Talanta. 2014;128:170–6.CrossRefGoogle Scholar
  36. 36.
    Arvand M, Zamani M, Sayyar AM. Rapid electrochemical synthesis of molecularly imprinted polymers on functionalized multi-walled carbon nanotubes for selective recognition of sunset yellow in food samples. Sensor Actuat B. 2017;243:927–39.CrossRefGoogle Scholar
  37. 37.
    Liu X, Zhang Z-H, Zhang H-B, Hu Y-F, Yang X, Nie L-H. Solid phase extraction of Ursolic acid using imprinted polymer modified multi-walled carbon nanotubes. Chinese J Anal Chem. 2011;39(6):839–45.CrossRefGoogle Scholar
  38. 38.
    Farrington K, Regan F. Investigation of the nature of MIP recognition: the development and characterisation of a MIP for ibuprofen. Biosens Bioelectron. 2007;22(6):1138–46.CrossRefGoogle Scholar
  39. 39.
    Zeng H, Wang Y, Liu X, Kong J, Nie C. Preparation of molecular imprinted polymers using bi-functional monomer and bi-crosslinker for solid-phase extraction of rutin. Talanta. 2012;93(2):172–81.CrossRefGoogle Scholar
  40. 40.
    Fayazi M, Taher MA, Afzali D, Mostafavi A. Preparation of molecularly imprinted polymer coated magnetic multi-walled carbon nanotubes for selective removal of dibenzothiophene. Mat Sci Semicon Proc. 2015;40:501–7.CrossRefGoogle Scholar
  41. 41.
    Li H, Xu W, Wang N, Ma X, Niu D, Jiang B, et al. Synthesis of magnetic molecularly imprinted polymer particles for selective adsorption and separation of dibenzothiophene. Microchim Acta. 2012;179(1):123–30.CrossRefGoogle Scholar
  42. 42.
    Chi W, Shi H, Shi W, Guo Y, Guo T. 4-nitrophenol surface molecularly imprinted polymers based on multiwalled carbon nanotubes for the elimination of paraoxon pollution. J Hazard Mater. 2012;227-228:243–9.CrossRefGoogle Scholar
  43. 43.
    Zhou Y, Zhou T, Jin H, Jing T, Song B, Zhou Y, et al. Rapid and selective extraction of multiple macrolide antibiotics in foodstuff samples based on magnetic molecularly imprinted polymers. Talanta. 2015;137:1–10.CrossRefGoogle Scholar
  44. 44.
    Niessen WM, Manini P, Andreoli R. Matrix effects in quantitative pesticide analysis using liquid chromatography-mass spectrometry. Mass Spectrom Rev. 2006;25(6):881–99.CrossRefGoogle Scholar
  45. 45.
    Schramm S, Leonco D, Hubert C, Tabet JC, Bridoux M. Development and validation of an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry method for the reliable quantification of 1,3,5-Triamino-2,4,6-trinitrobenzene (TATB) and 14 other explosives and their degradation products in environmental water samples. Talanta. 2015;143:271–8.CrossRefGoogle Scholar
  46. 46.
    Hosoya K, Yoshizako K, Tanaka N, Kimata K, Araki T, Haginaka J. Uniform-size macroporous polymer-based stationary phase for HPLC prepared through molecular imprinting technique. Chem Lett. 1994;8(8):1437–8.CrossRefGoogle Scholar
  47. 47.
    Buhrman DL, Price PI, Rudewiczcor PJ. Quantitation of SR 27417 in human plasma using electrospray liquid chromatography-tandem mass spectrometry: a study of ion suppression. J Am Soc Mass Spectr. 1996;7(11):1099–105.CrossRefGoogle Scholar
  48. 48.
    Janusch F, Scherz G, Mohring SA, Stahl J, Hamscher G. Comparison of different solid-phase extraction materials for the determination of fluoroquinolones in chicken plasma by LC-MS/MS. J Chromatogr B. 2014;951-952(1):149–56.CrossRefGoogle Scholar
  49. 49.
    Racamonde I, Rodil R, Quintana JB, Villaverde-de-Saa E, Cela R. Determination of benzodiazepines, related pharmaceuticals and metabolites in water by solid-phase extraction and liquid-chromatography-tandem mass spectrometry. J Chromatogr A. 2014;1352:69–79.CrossRefGoogle Scholar
  50. 50.
    Wang T, Wang J, Zhang C, Yang Z, Dai X, Cheng M, et al. Metal-organic framework MIL-101(Cr) as a sorbent of porous membrane-protected micro-solid-phase extraction for the analysis of six phthalate esters from drinking water: a combination of experimental and computational study. Analyst. 2015;140(15):5308–16.CrossRefGoogle Scholar
  51. 51.
    Martinezsena T, Armenta S, Guardia M, Esteveturrillas FA. Determination of non-steroidal anti-inflammatory drugs in water and urine using selective molecular imprinted polymer extraction and liquid chromatography. J Pharmaceut Biomed. 2016;131:48–53.CrossRefGoogle Scholar
  52. 52.
    Dong B, Hu J. Dissipation and residue determination of fluopyram and tebuconazole residues in watermelon and soil by GC-MS. Int J Environ An Ch. 2014;94(5):493–505.CrossRefGoogle Scholar
  53. 53.
    Gan J, Lv L, Peng J, Li J, Xiong Z, Chen D, et al. Multi-residue method for the determination of organofluorine pesticides in fish tissue by liquid chromatography triple quadrupole tandem mass spectrometry. Food Chem. 2016;207:195–204.CrossRefGoogle Scholar
  54. 54.
    Jensen GG, Bjorklund E, Simonsen A, Halling-Sorensen B. Determination of 2,6-dichlorobenzamide and its degradation products in water samples using solid-phase extraction followed by liquid chromatography-tandem mass spectrometry. J Chromatogr A. 2009;1216(27):5199–206.CrossRefGoogle Scholar
  55. 55.
    Nakada N, Tanishima T, Shinohara H, Kiri K, Takada H. Pharmaceutical chemicals and endocrine disrupters in municipal wastewater in Tokyo and their removal during activated sludge treatment. Water Res. 2006;40(17):3297–303.CrossRefGoogle Scholar
  56. 56.
    Falås P, Andersen HR, Ledin A, JlC J. Impact of solid retention time and nitrification capacity on the ability of activated sludge to remove pharmaceuticals. Environ Technol. 2012;33(8):865.CrossRefGoogle Scholar
  57. 57.
    Verlicchi P, Aukidy MA, Zambello E. Occurrence of pharmaceutical compounds in urban wastewater: removal, mass load and environmental risk after a secondary treatment—a review. Sci Total Environ. 2012;429(7):123.CrossRefGoogle Scholar
  58. 58.
    Koumaki E, Mamais D, Noutsopoulos C. Environmental fate of non-steroidal anti-inflammatory drugs in river water/sediment systems. J Hazard mater. 2016;323(2):233–241.Google Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Pharmaceutical Analysis, School of PharmacyShenyang Pharmaceutical UniversityShenyangChina

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