Analytical and Bioanalytical Chemistry

, Volume 411, Issue 10, pp 2019–2029 | Cite as

Fluorescent kinetics combined with fourth-order calibration for the determination of diclofenac sodium in environmental water

  • Jiao Li
  • Jie Xu
  • Wenying Jin
  • Zhongsheng YiEmail author
  • Chenbo Cai
  • Xuefen Huang
  • Jinfang NieEmail author
  • Yun Zhang
Research Paper


A method that combines five-way fluorescence kinetics with fourth-order calibration for interference-free quantification of diclofenac sodium in river water was proposed and tested. Traditional fluorescence methods may not be suitable for such measurements since the fluorescence properties of the analyte are highly dependent on both pH and irradiation time in situ. In the method considered here, a five-way emission-excitation-time-pH data array was obtained from the samples by introducing the pH level and irradiation time as two extra modes. Then the data array was resolved by three fourth-order calibration algorithms: alternating fitting weighted residue quinquelinear decomposition (AFWRQQLD), five-way parallel factor analysis (five-PARAFAC), and alternating quinquelinear decomposition (AQQLD). The average recoveries and detection limits calculated for diclofenac sodium in a set of analyte-spiked river water samples using AFWRQQLD, five-PARAFAC, and AQQLD were 97.2 ± 3.2% and 1.9 ng mL−1, 96.8 ± 3.0% and 4.0 ng mL−1, and 92.6 ± 2.7% and 2.5 ng mL−1, respectively. A study of other figures of merit, statistical analysis, an elliptical joint confidence region test, and a t-test were additionally carried out to validate the analytical performance of the proposed method in detail. The results demonstrated that this new method required only two steps (fluorescence measurement and algorithm analysis) to determine the analyte concentration. It could therefore provide the basis for developing novel reliable and sensitive approaches for the accurate detection of pharmaceutical pollutants with unstable fluorescence properties in real complex matrices such as environmental water samples.

Graphical Abstract


Environmental monitoring Drug analysis Fluorescence kinetics High-order calibration Diclofenac sodium 



The authors would like to acknowledge financial support from the National Natural Science Foundation of China (nos. 21765007, 21665002, and 21565012), Guangxi Key Research and Development Project (no. GuikeAB17129003), and Project of High Level Innovation Team/Outstanding Scholar and Key Laboratory of Food Safety and Detection in Guangxi Colleges and Universities (no. 2015GXNSFFA139005). They are also grateful to Dr. Amit Fischer of the Hebrew University of Jerusalem for helping to revise the manuscript, especially the grammar.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflicts of interest.

Supplementary material

216_2019_1624_MOESM1_ESM.pdf (509 kb)
ESM 1 (PDF 509 kb)


  1. 1.
    Hofmann J, Freier U, Wecks M, Hohmann S. Degradation of diclofenac in water by heterogeneous catalytic oxidation with H2O2. Appl Catal B Environ. 2007;70(1):447–51.
  2. 2.
    Schwarzenbach RP, Escher BI, Fenner K, Hofstetter TB, Johnson CA, Gunten U, et al. The challenge of micropollutants in aquatic systems. Science. 2006;313(5790):1072–7.
  3. 3.
    Ma L, Liu Y, Zhang J, Yang Q, Li G, Zhang D. Impacts of irrigation water sources and geochemical conditions on vertical distribution of pharmaceutical and personal care products (PPCPs) in the vadose zone soils. Sci Total Environ. 2018;626:1148–56. Scholar
  4. 4.
    Wang J, Wang S. Removal of pharmaceuticals and personal care products (PPCPs) from wastewater: a review. J Environ Manag. 2016;182:620–40. Scholar
  5. 5.
    Liu JL, Wong MH. Pharmaceuticals and personal care products (PPCPs): a review on environmental contamination in China. Environ Int. 2013;59(3):208–24. Scholar
  6. 6.
    Tamura I, Yasuda Y, Kagota KI, Yoneda S, Nakada N, Kumar V, et al. Contribution of pharmaceuticals and personal care products (PPCPs) to whole toxicity of water samples collected in effluent-dominated urban streams. Ecotox Environ Safe. 2017;144:338–50.
  7. 7.
    Lin T, Yu S, Chen W. Occurrence, removal and risk assessment of pharmaceutical and personal care products (PPCPs) in an advanced drinking water treatment plant (ADWTP) around Taihu Lake in China. Chemosphere. 2016;152:1–9. Scholar
  8. 8.
    Roberts J, Kumar A, Du J, Hepplewhite C, Ellis DJ, Christy AG, et al. Pharmaceuticals and personal care products (PPCPs) in Australia’s largest inland sewage treatment plant, and its contribution to a major Australian river during high and low flow. Sci Total Environ. 2016;541(3):1625–37.
  9. 9.
    Kallenborn R, Brorström-Lundén E, Reiersen LO, Wilson S. Pharmaceuticals and personal care products (PPCPs) in Arctic environments: indicator contaminants for assessing local and remote anthropogenic sources in a pristine ecosystem in change. Environ Sci Pollut Res Int. 2018;25(33):33001–13.
  10. 10.
    Dai G, Wang B, Fu C, Dong R, Huang J, Deng S, et al. Pharmaceuticals and personal care products (PPCPs) in urban and suburban rivers of Beijing, China: occurrence, source apportionment and potential ecological risk. Environ Sci Process Impacts. 2016;18(4):445–55.
  11. 11.
    Wang H, Shen Y, Hu C, Xing X, Zhao D. Sulfadiazine/ciprofloxacin promote opportunistic pathogens occurrence in bulk water of drinking water distribution systems. Environ Pollut. 2017;234:71–8. Scholar
  12. 12.
    Prutthiwanasan B, Phechkrajang C, Suntornsuk L. Fluorescent labelling of ciprofloxacin and norfloxacin and its application for residues analysis in surface water. Talanta. 2016;159:74–9. Scholar
  13. 13.
    Rolando B, Lazzarato L, Donnola M, Marini E, Joseph S, Morini G. Pozzoli. C, Fruttero R, Gasco A. Water-soluble nitric-oxide-releasing acetylsalicylic acid (ASA) prodrugs. ChemMedChem. 2013;8(7):1199–209.
  14. 14.
    Xiao P, Weibel N, Dudal Y, Corvini PFX, Shahgaldian P. A cyclodextrin-based polymer for sensing diclofenac in water. J Hazard Mater. 2015;299:412–6 Scholar
  15. 15.
    Vergili I. Application of nanofiltration for the removal of carbamazepine, diclofenac and ibuprofen from drinking water sources. J Environ Manag. 2013;127(2):177–87. Scholar
  16. 16.
    Daneshvar A, Aboulfadl K, Viglino L. Evaluating pharmaceuticals and caffeine as indicators of fecal contamination in drinking water sources of the greater Montreal region. Chemosphere. 2012;88(1):131–9. Scholar
  17. 17.
    Johnson AC, Dumont E, Williams RJ, Oldenkamp R, Cisowska I, Sumpter JP. Do concentrations of ethinylestradiol, estradiol, and diclofenac in European rivers exceed proposed EU environmental quality standards? Environ Sci Technol. 2013;47(21):12297–304. Scholar
  18. 18.
    Pimenta AM, Araújo AN, Montenegro MCBSM. Simultaneous potentiometric and fluorimetric determination of diclofenac in a sequential injection analysis system. Anal Chim Acta. 2002;470(2):185–94.
  19. 19.
    Blom N, Sygusch J. Energetically favorable binding site determination between two molecules. USP 5866343. 1999.Google Scholar
  20. 20.
    Deng A, Himmelsbach M, Zhu QZ, Frey S, Sengl M, Buchberger W, et al. Residue analysis of the pharmaceutical diclofenac in different water types using ELISA and GC−MS. Environ Sci Technol. 2003;37(15):3422–9.
  21. 21.
    Agüera A, Mezcua M, Mochol F, Vargas-Berenguel A, Fernández-Alba AR. Application of gas chromatography-hybrid chemical ionization mass spectrometry to the analysis of diclofenac in wastewater samples. J Chromatogr A. 2006;1133(1):287–92.
  22. 22.
    Osorio V, Imbertbouchard M, Zonja B, Abad JL, Pérez S, Barceló D. Simultaneous determination of diclofenac, its human metabolites and microbial nitration/nitrosation transformation products in wastewaters by liquid chromatography/quadrupole-linear ion trap mass spectrometry. J Chromatogr A. 2014;1347(15):63–71. Scholar
  23. 23.
    Malá Z, Gebauer P, Boček P. Capillary isotachophoresis with ESI-MS detection: methodology for highly sensitive analysis of ibuprofen and diclofenac in waters. Anal Chim Acta. 2016;907(5):1–6. Scholar
  24. 24.
    Manzo V, Ulisse K, Rodríguez I, Pereira E, Richter P. A molecularly imprinted polymer as the sorptive phase immobilized in a rotating disk extraction device for the determination of diclofenac and mefenamic acid in wastewater. Anal Chim Acta. 2015;889:130–7. Scholar
  25. 25.
    Huebner M, Weber E, Niessner R, Boujday S, Knopp D. Rapid analysis of diclofenac in freshwater and wastewater by a monoclonal antibody-based highly sensitive ELISA. Anal Bioanal Chem. 2015;407(29):8873–82. Scholar
  26. 26.
    Lonappan L, Publicharla R, Rouissi T, Brar SK, Verma M, Surampalli RY, et al. Diclofenac in municipal wastewater treatment plant: quantification using laser diode thermal desorption--atmospheric pressure chemical ionization--tandem mass spectrometry approach in comparison with an established liquid chromatography-electrospray ionization-tandem mass spectrometry method. J Chromatogr A. 2016;1433:106–13.
  27. 27.
    Madikizela LM, Chimuka L. Simultaneous determination of naproxen, ibuprofen and diclofenac in wastewater using solid-phase extraction with high performance liquid chromatography. Water SA. 2017;43(2):264–74. Scholar
  28. 28.
    Aydin S, Aydin ME, Beduk F, Tekinay A, Kilic H. Analysis of diclofenac in water samples using in situ derivatization-vortex-assisted liquid-liquid microextraction with gas chromatography-mass spectrometry. Acta Pharma. 2018;68:313–24. Scholar
  29. 29.
    Schmidt S, Hoffmann H, Garbe LA, Schneider RJ. Liquid chromatography-tandem mass spectrometry detection of diclofenac and related compounds in water samples. J Chromatogr A. 2018;1538:112–6. Scholar
  30. 30.
    Hassan SSM, Abdelaziz RM, Abdelsamad MS. Plastic membrane electrode for selective determination of diclofenac (voltaren) in pharmaceutical preparations. Analyst. 1994;119(9):1993–6. Scholar
  31. 31.
    Kamath BV, Shivram K. Spectrophotometric determination of diclofenac sodium via oxidation reactions. Anal Lett. 1993;26(5):903–11. Scholar
  32. 32.
    Botello JC, Pérezcaballero G. Spectrophotometric determination of diclofenac sodium with methylene blue. Talanta. 1995;42(1):105–8. Scholar
  33. 33.
    Damiani PC, Bearzotti M, Cabezón MA, Olivieri AC. Spectrofluorometric determination of diclofenac in tablets and ointments. J Pharmaceut Biomed. 1999;20(3):587–90. Scholar
  34. 34.
    Bro R. Review on multiway analysis in chemistry: 2000–2005. Anal Chem. 2006;36(3–4):279–93.
  35. 35.
    Bro R. Multi-way analysis in the food industry: models, algorithms, and applications. Doctoral thesis. Amsterdam: Universiteit van Amsterdam; 1998.Google Scholar
  36. 36.
    Chen ZP, Wu HL, Jiang JH, Li Y, Yu RQ. A novel trilinear decomposition algorithm for second-order linear calibration. Chemometr Intell Lab Syst. 2000;52(1):75–86. Scholar
  37. 37.
    Sanchez E, Kowalski BR. Tensorial resolution: a direct trilinear decomposition. J Chemom. 1990;4(1):29–45. Scholar
  38. 38.
    Maggio RM, Peña AMDL, Olivieri AC. Unfolded partial least-squares with residual quadrilinearization: a new multivariate algorithm for processing five-way data achieving the second-order advantage. Application to fourth-order excitation-emission-kinetic-pH fluorescence analytical data. Chemometr Intell Lab Syst. 2011;109(2):178–85. Scholar
  39. 39.
    Zhu SH, Wu HL, Xia AL, Nie JF, Bian YC, Cai CB, et al. Excitation-emission-kinetic fluorescence coupled with third-order calibration for quantifying carbaryl and investigating the hydrolysis in effluent water. Talanta. 2009;77(5):1640–6.
  40. 40.
    Kang C, Wu HL, Yu YJ, Liu YJ, Zhang SR, Zhang XH, et al. An alternative quadrilinear decomposition algorithm for four-way calibration with application to analysis of four-way fluorescence excitation-emission-pH data array. Anal Chim Acta. 2013;758(1):45–57.
  41. 41.
    Rodríguez N, Ortiz MC, Sarabia LA. Fluorescence quantification of tetracycline in the presence of quenching matrix effect by means of a four-way model. Talanta. 2009;77(3):1129–36. Scholar
  42. 42.
    Wu HL, Shibukawa M, Oguma K. An alternating trilinear decomposition algorithm with application to calibration of HPLC–DAD for simultaneous determination of overlapped chlorinated aromatic hydrocarbons. J Chemom. 1998;12(1):1–26.<1::AID-CEM492>3.0.CO;2-4.CrossRefGoogle Scholar
  43. 43.
    Xia AL, Wu HL, Fang DM, Ding YJ, Hu LQ, Yu RQ. Alternating penalty trilinear decomposition algorithm for second-order calibration with application to interference-free analysis of excitation–emission matrix fluorescence data. J Chemom. 2010;19(2):65–76. Scholar
  44. 44.
    Jiang JH, Wu HL, Chen ZP, Yu RQ. Coupled vectors resolution method for chemometric calibration with three-way data. Anal Chem. 1999;71(19):4254–62. Scholar
  45. 45.
    Jiang JH, Wu HL, Li Y, Yu RQ. Alternating coupled vectors resolution (ACOVER) method for trilinear analysis of three-way data. J Chemom. 2015;13(6):557–78.<557::AID-CEM563>3.0.CO;2-C.CrossRefGoogle Scholar
  46. 46.
    Li Y, Jiang JH, Wu HL, Chen ZP. Alternating coupled matrices resolution method for three-way arrays analysis. Chemometr Intell Lab Syst. 2000;52(1):33–43. Scholar
  47. 47.
    Fu HY, Wu HL, Yu YJ, Yu LL, Zhang SR, Nie JF, et al. A new third-order calibration method with application for analysis of four-way data arrays. J Chemom. 2011;25(8):408–29.
  48. 48.
    Nie JF, Li B, Zhang Y, Fan JL, Yi ZS, Cai ZR. High-order calibration for the spectrofluorimetric determination of pesticides based on photochemical derivatization. A solution of the problems of inner-filter effects and matrix interferences in complex environmental water. Chemometr Intell Lab Syst. 2016;156:36–53.
  49. 49.
    Paatero P. A weighted non-negative least squares algorithm for three-way PARAFAC factor analysis. Chemometr Intell Lab Syst. 1997;38:223–42. Scholar
  50. 50.
    Qing XD, Wu HL, Zhang XH, Li Y, Gu HW, Yu RQ. A novel fourth-order calibration method based on alternating quinquelinear decomposition algorithm for processing high performance liquid chromatography-diode array detection- kinetic-pH data of naptalam hydrolysis. Anal Chim Acta. 2015;861:12–24. Scholar
  51. 51.
    Tomic I, Vidis-Millward A, Mueller-Zsigmondy M, Cardot JM. Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism. Int J Pharm. 2016;505:42–51. Scholar
  52. 52.
    Nie JF, Wu HL, Zhu SH, Han QJ, Fu HY, Li SF, et al. Simultaneous determination of 6-methylcoumarin and 7-methoxycoumarin in cosmetics using three-dimensional excitation-emission matrix fluorescence coupled with second-order calibration methods. Talanta. 2008;75(5):1260–9.
  53. 53.
    Leurgans S, Ross RT. Multilinear models: applications in spectroscopy. Stat Sci. 1992;7:289–310. Scholar
  54. 54.
    Mehta SK, Bhasin KK, Dham S. Energetically favorable interactions between diclofenac sodium and cyclodextrin molecules in aqueous media. J Colloid Interf Sci. 2008;326(2):374–81. Scholar
  55. 55.
    Kozlowska M, Rodziewicz P, Utesch T, Mroginski MA, Kaczmarekkedziera A. Solvation of diclofenac in water from atomistic molecular dynamics simulations—interplay between solute-solute and solute-solvent interactions. Phys Chem Chem Phys. 2018;20(13):8629–39.
  56. 56.
    Huguet A, Vacher L, Relexans S, Saubusse S, Froidefond JM, Parlanti E. Properties of fluorescent dissolved organic matter in the Gironde estuary. Org Geochem. 2009;40(6):706–19. Scholar
  57. 57.
    Arancibia JA, Escandar GM. Two different strategies for the fluorimetric determination of piroxicam in serum. Talanta. 2003;60(6):1113–21. Scholar
  58. 58.
    González AG, Herrador MA, Asuero AG. Intra-laboratory testing of method accuracy from recovery assays. Talanta. 1999;48(3):729–36. Scholar
  59. 59.
    Schmidt J, Klingler FM, Proschak E, Steinhilber D, Schubert-Zsilavecz MD. NSAIDs ibuprofen, indometacin, and diclofenac do not interact with farnesoid X receptor. Sci Rep. 2015;5:14782–1–12. Scholar
  60. 60.
    Zhang J, Sun HH, Zhang YZ, Yang LY, Dai J, Liu Y. Interaction of human serum albumin with indomethacin: spectroscopic and molecular modeling studies. J Solut Chem. 2012;41(3):422–35. Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.College of Chemistry and BioengineeringGuilin University of TechnologyGuilinChina
  2. 2.College of Chemistry and Life SciencesChuxiong Normal UniversityChuxiongChina

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