Abstract
Cytostatic compounds are an important group of micro-pollutants since they are used to kill cells or stop cell division. For this reason, they are also considered mutagenic. Several cytostatic compounds have been detected in hospital effluents, in the influents and effluents of wastewater treatment plants and even in river water. However, their detection in solid matrices is very scarce. In this work, we have developed a new procedure based on microwave-assisted extraction (MAE) for the extraction of cytostatic compounds from sludge and sediment before determination by ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC–MS/MS). To develop this procedure, we have chosen a group of eight widely used cytostatic compounds and carried out a systematic experimental design to optimize the extraction conditions. Under these optimal conditions, the studied cytostatic compounds are extracted with good sensitivity, with recoveries ranging from 65 to 122% in sludge and recoveries varying between 49 and 109% in sediment, with the exception of etoposide, which has a lower recovery from these types of samples. The limits of detection were from 0.42 to 79.8 ng g−1 in sludge and from 0.10 to 87.5 ng g−1 in sediment. Intraday and interday relative standard deviations (RSDs) were below 15% and 18%, respectively, in both matrices at the tested concentrations. The total procedure was applied to samples of sludge taken from the main wastewater treatment plant (WWTP) of the island of Gran Canaria (Spain) and for sediment samples obtained close to the marine outfalls of different wastewater treatment plants for the same island.
Similar content being viewed by others
References
Besse J-P, Latour J-F, Garric J. Anticancer drugs in surface waters: what can we say about the occurrence and environmental significance of cytotoxic, cytostatic and endocrine therapy drugs? Environ Int. 2012;39:73–86. https://doi.org/10.1016/j.envint.2011.10.002.
Borgatta M, Decosterd L-A, Waridel P, Buclin T, Chèvre N. The anticancer drug metabolites endoxifen and 4-hydroxy-tamoxifen induce toxic effects on Daphnia pulex in a two-generation study. Sci Total Environ. 2015;520:232–40. https://doi.org/10.1016/j.scitotenv.2015.03.040.
Kovács R, Csenki Z, Bakos K, Urbányi B, Horváth Á, Garaj-Vrhovac V, et al. Assessment of toxicity and genotoxicity of low doses of 5-fluorouracil in zebrafish (Danio rerio) two-generation study. Water Res. 2015;77:201–12. https://doi.org/10.1016/j.watres.2015.03.025.
Borgatta M, Waridel P, Decosterd L-A, Buclin T, Chèvre N. Multigenerational effects of the anticancer drug tamoxifen and its metabolite 4-hydroxy-tamoxifen on Daphnia pulex. Sci Total Environ. 2016;545–546:21–9. https://doi.org/10.1016/j.scitotenv.2015.11.155.
Trombini C, Garcia da Fonseca T, Morais M, Rocha TL, Blasco J, Bebianno MJ. Toxic effects of cisplatin cytostatic drug in mussel Mytilus galloprovincialis. Mar Environ Res. 2016;119:12–21. https://doi.org/10.1016/j.marenvres.2016.05.004.
Russo C, Isidori M, Deaver JA, Poynton HC. Toxicogenomic responses of low level anticancer drug exposures in Daphnia magna. Aquat Toxicol. 2018;203:40–50. https://doi.org/10.1016/j.aquatox.2018.07.010.
Yin J, Shao B, Zhang J, Li K. A preliminary study on the occurrence of cytostatic drugs in hospital effluents in Beijing, China. Bull Environ Contam Toxicol. 2010;84:39–45. https://doi.org/10.1007/s00128-009-9884-4.
Martín J, Camacho-Muñoz D, Santos JL, Aparicio I, Alonso E. Simultaneous determination of a selected group of cytostatic drugs in water using high-performance liquid chromatography–triple-quadrupole mass spectrometry. J Sep Sci. 2011;34:3166–77. https://doi.org/10.1002/jssc.201100461.
Ferrando-Climent L, Rodriguez-Mozaz S, Barceló D. Development of a UPLC-MS/MS method for the determination of ten anticancer drugs in hospital and urban wastewaters, and its application for the screening of human metabolites assisted by information-dependent acquisition tool (IDA) in sewage samples. Anal Bioanal Chem. 2013;405:5937–52. https://doi.org/10.1007/s00216-013-6794-4.
Negreira N, Mastroianni N, López de Alda M, Barceló D. Multianalyte determination of 24 cytostatics and metabolites by liquid chromatography–electrospray–tandem mass spectrometry and study of their stability and optimum storage conditions in aqueous solution. Talanta. 2013;116:290–9. https://doi.org/10.1016/j.talanta.2013.04.070.
Franquet-Griell H, Cornadó D, Caixach J, Ventura F, Lacorte S. Determination of cytostatic drugs in Besòs River (NE Spain) and comparison with predicted environmental concentrations. Environ Sci Pollut Res. 2017:1–12. https://doi.org/10.1007/s11356-016-8337-y.
Kümmerer K, Al-Ahmad A, Bertram B, Wießler M. Biodegradability of antineoplastic compounds in screening tests: influence of glucosidation and of stereochemistry. Chemosphere. 2000;40:767–73. https://doi.org/10.1016/S0045-6535(99)00451-8.
Lenz K, Mahnik SN, Weissenbacher N, Mader RM, Krenn P, Hann S, et al. Monitoring, removal and risk assessment of cytostatic drugs in hospital wastewater. Water Sci Technol. 2007;56:141–9.
Lenz K, Koellensperger G, Hann S, Weissenbacher N, Mahnik SN, Fuerhacker M. Fate of cancerostatic platinum compounds in biological wastewater treatment of hospital effluents. Chemosphere. 2007;69:1765–74. https://doi.org/10.1016/j.chemosphere.2007.05.062.
Santana-Viera S, Montesdeoca-Esponda S, Sosa-Ferrera Z, Santana-Rodríguez JJ. Cytostatic drugs in environmental samples: an update on the extraction and determination procedures. TrAC Trends Anal Chem. 2016;80:373–86. https://doi.org/10.1016/j.trac.2015.08.016.
Ternes TA, Bonerz M, Herrmann N, Löffler D, Keller E, Lacida BB, et al. Determination of pharmaceuticals, iodinated contrast media and musk fragrances in sludge by LC tandem MS and GC/MS. J Chromatogr A. 2005;1067:213–23. https://doi.org/10.1016/j.chroma.2004.10.096.
Okuda T, Yamashita N, Tanaka H, Matsukawa H, Tanabe K. Development of extraction method of pharmaceuticals and their occurrences found in Japanese wastewater treatment plants. Environ Int. 2009;35:815–20. https://doi.org/10.1016/j.envint.2009.01.006.
Seira J, Claparols C, Joannis-Cassan C, Albasi C, Montréjaud-Vignoles M, Sablayrolles C. Optimization of pressurized liquid extraction using a multivariate chemometric approach for the determination of anticancer drugs in sludge by ultra high performance liquid chromatography–tandem mass spectrometry. J Chromatogr A. 2013;1283:27–38. https://doi.org/10.1016/j.chroma.2013.01.114.
Peysson W, Vulliet E. Determination of 136 pharmaceuticals and hormones in sewage sludge using quick, easy, cheap, effective, rugged and safe extraction followed by analysis with liquid chromatography–time-of-flight-mass spectrometry. J Chromatogr A. 2013;1290:46–61. https://doi.org/10.1016/j.chroma.2013.03.057.
López Zavala MÁ, Reynoso-Cuevas L. Simultaneous extraction and determination of four different groups of pharmaceuticals in compost using optimized ultrasonic extraction and ultrahigh pressure liquid chromatography–mass spectrometry. J Chromatogr A. 2015;1423:9–18. https://doi.org/10.1016/j.chroma.2015.10.051.
Azuma T, Arima N, Tsukada A, Hirami S, Matsuoka R, Moriwake R, et al. Distribution of six anticancer drugs and a variety of other pharmaceuticals, and their sorption onto sediments, in an urban Japanese river. Environ Sci Pollut Res. 2017;24:19021–30. https://doi.org/10.1007/s11356-017-9525-0.
Santana-Viera S, Hernández-Arencibia P, Sosa-Ferrera Z, Santana-Rodríguez JJ. Simultaneous and systematic analysis of cytostatic drugs in wastewater samples by ultra-high performance liquid chromatography tandem mass spectrometry. J Chromatogr B. 2019;1110–1111:124–32. https://doi.org/10.1016/j.jchromb.2019.02.018.
Guedes-Alonso R, Santana-Viera S, Montesdeoca-Esponda S, Afonso-Olivares C, Sosa-Ferrera Z, Santana-Rodríguez JJ. Application of microwave-assisted extraction and ultra-high performance liquid chromatography–tandem mass spectrometry for the analysis of sex hormones and corticosteroids in sewage sludge samples. Anal Bioanal Chem. 2016;408:6833–44. https://doi.org/10.1007/s00216-016-9810-7.
Chemicalize - Methotrexate. https://chemicalize.com/#/calculation. Accessed 27 Feb 2018.
Chemicalize - Cyclophosphamide. https://chemicalize.com/#/calculation. Accessed 27 Feb 2018.
Chemicalize - 5 Fluorouracil. https://chemicalize.com/#/calculation. Accessed 27 Feb 2018.
Chemicalize - Etoposide. https://chemicalize.com/#/calculation. Accessed 27 Feb 2018.
Chemicalize - Gemcitabine. https://chemicalize.com/#/calculation. Accessed 27 Feb 2018.
Chemicalize - Tamoxifen. https://chemicalize.com/#/calculation. Accessed 27 Feb 2018.
Chemicalize - Vinblastine. https://chemicalize.com/#/calculation. Accessed 27 Feb 2018.
Chemicalize - Vincristine. https://chemicalize.com/#/calculation. Accessed 27 Feb 2018.
Health UD of, Human Services F, administration D (2001) Bioanalytical method validation, guidance for industry. http://www.fda.gov/cder/guidance/4252fnl.htm. Accessed 24 Feb 2020.
Dorival-García N, Zafra-Gómez A, Camino-Sánchez FJ, Navalón A, Vílchez JL. Analysis of quinolone antibiotic derivatives in sewage sludge samples by liquid chromatography–tandem mass spectrometry: comparison of the efficiency of three extraction techniques. Talanta. 2013;106:104–18. https://doi.org/10.1016/j.talanta.2012.11.080.
Dorival-García N, Labajo-Recio C, Zafra-Gómez A, Juárez-Jiménez B, Vílchez JL. Improved sample treatment for the determination of 17 strong sorbed quinolone antibiotics from compost by ultra high performance liquid chromatography tandem mass spectrometry. Talanta. 2015;138:247–57. https://doi.org/10.1016/j.talanta.2015.03.011.
Evans SE, Davies P, Lubben A, Kasprzyk-Hordern B. Determination of chiral pharmaceuticals and illicit drugs in wastewater and sludge using microwave assisted extraction, solid-phase extraction and chiral liquid chromatography coupled with tandem mass spectrometry. Anal Chim Acta. 2015;882:112–26. https://doi.org/10.1016/j.aca.2015.03.039.
Tong L, Liu H, Xie C, Li M. Quantitative analysis of antibiotics in aquifer sediments by liquid chromatography coupled to high resolution mass spectrometry. J Chromatogr A. 2016;1452:58–66. https://doi.org/10.1016/j.chroma.2016.05.027.
Speltini A, Sturini M, Maraschi F, Viti S, Sbarbada D, Profumo A. Fluoroquinolone residues in compost by green enhanced microwave-assisted extraction followed by ultra performance liquid chromatography tandem mass spectrometry. J Chromatogr A. 2015;1410:44–50. https://doi.org/10.1016/j.chroma.2015.07.093.
Snow DD, Damon-Powell T, Onanong S, Cassada DA. Sensitive and simplified analysis of natural and synthetic steroids in water and solids using on-line solid-phase extraction and microwave-assisted solvent extraction coupled to liquid chromatography tandem mass spectrometry atmospheric pressure photoionization. Anal Bioanal Chem. 2013;405:1759–71. https://doi.org/10.1007/s00216-012-6572-8.
Montesdeoca-Esponda S, Sosa-Ferrera Z, Santana-Rodríguez JJ. Microwave-assisted extraction combined with on-line solid phase extraction followed by ultra-high-performance liquid chromatography with tandem mass spectrometric determination of benzotriazole UV stabilizers in marine sediments and sewage sludges. J Sep Sci. 2013;36:781–8. https://doi.org/10.1002/jssc.201200664.
Acknowledgements
This work was supported by funds provided by the Spanish Ministry of Economy and Competitiveness [Research Project CTM2015-66095-C2-1-R]. Jozef Tuček and Radoslav Halko thank also the Scientific Grant Agency of the Ministry of Education of the Slovak Republic, VEGA no. 1/0678/19, for the development of this work. Sergio Santana-Viera thanks the University of Las Palmas de Gran Canaria (Spain) for his Ph.D. student grant. We must also thank the WWTP for the samples provided.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(PDF 313 kb)
Rights and permissions
About this article
Cite this article
Santana-Viera, S., Tuček, J., Torres-Padrón, M.E. et al. Cytostatic compounds in sludge and sediment: extraction and determination by a combination of microwave-assisted extraction and UHPLC–MS/MS. Anal Bioanal Chem 412, 3639–3651 (2020). https://doi.org/10.1007/s00216-020-02600-0
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00216-020-02600-0