{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:51834"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:51834","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Cytostatics in the aquatic environment : analysis, occurrence, and possibilities for removal","abstract":"Many pharmaceuticals have attracted the attention of environmental scientists and are of concern due to their observed occurrence in surface water, ground water, drinking water, sediment, and soil. Further investigations have considered their removal efficiencies in wastewater treatment processes and their ecotoxicological effects. Cytostatics are a class of pharmaceuticals used in the treatment of cancer and have the potential to negatively impact the environment. It is hypothesized that due to their mode of action, practically all eukaryotic organisms are vulnerable to damage, with teratogenicity being the greatest concern at low ng/L levels. This thesis will discuss the contributions to this field in the form of 1) development of a method for chemical analysis of cytostatics in wastewater, 2) occurrence studies, and 3) potential for removal with advanced treatment processes. To expand the knowledge on the environmental occurrence of cytostatics and to compliment a range of cytostatics for which occurrence data are available, a solid phase extraction and HPLC-MS/MS method was established for highly consumed cytostatics 5 fluorouracil, cytarabine, and gemcitabine and the human metabolites uracil 1-beta-d-arabinofuranoside and 2’,2’-difluorodeoxyuridine. Hydrophilic interaction chromatography (HILIC), a chromatography for polar analytes in aqueous samples, was used to achieve a good retention of the polar analytes. Along with the method development, retention mechanisms on the HILIC stationary phase were studied. Both partitioning and adsorption play a role in the retention on the tested sulfoalkylbetaine modified silica HILIC column material. The contribution of these two processes changes over the 1.6-40% range of water in the mobile phase. Although the specific break point is difficult to determine, adsorption becomes more significant as the fraction of water in the mobile phase decreases below approximately 16%. Wastewater from a Swiss hospital was monitored for 5-fluorouracil, gemcitabine and 2’,2’-difluorodeoxyuridine (metabolite of gemcitabine). The limits of quantification were 5.0, 0.9, and 9.0 ng/L and the maximum concentrations detected were 27, 38, and 840 ng/L, respectively. Emission levels within one day and over several days were found to correlate with the pharmacokinetic excretion pattern and the consumed amounts in the hospital during these days. On average, 1.1%, 1.4% and 3.7% of the total excreted amounts of the cytostatics 5 fluorouracil, gemcitabine and 2',2'-difluorodeoxyuridine were found in the hospital wastewater, respectively. Due to low recoveries, stability studies were performed and showed that the half-lives of the analytes in the raw wastewater are very short: 1.0, 0.7 and 2.5 hours, respectively. Environmental impact of 5-fluorouracil, gemcitabine and 2’,2’ difluorodeoxy-uridine seem to be of minor importance, as the environmental risk assessment quotients PEC/PNEC are protective (in orders of magnitude of 10e-3 - 10e-6). Nevertheless, cytostatics are a special group of pharmaceuticals with carcinogenic potency and until data with specific tests and end-points designed especially for this class of pharmaceuticals are available, the precautionary principle should be applied. To study removal possibilities, sorption to powdered activated carbon was investigated. Adsorption is an effective process for the removal of hydrophobic substances from water. Employing it as a wastewater treatment process, polar compounds may also be simultaneously removed to a certain extent. Laboratory scale batch experiments were performed to evaluate the adsorption kinetics and isotherm data of 5-fluorouracil and cytarabine on two powdered activated carbons, Norit SAE Super and Activated Lignite HOK Super. The results of the adsorption characterization were compared with those of two hydrophobic substances, bisphenol A and 17-alpha-ethinylestradiol, produced with the identical experimental conditions and matrix. A dose of 30 mg.L-1 of Norit SAE Super that resulted in removal of the two hydrophobic control compounds below 1% was found to remove 30 and 65% of 5-fluorouracil and cytarabine, respectively. Influence of the solution pH, ionic strength, temperature, and presence of matrix compounds competing for the sorption sites was studied on one of the tested powdered activated carbons, showing that the extent of the competing compounds’ influence is the greatest. Applying a pseudo single-solute isotherm and a concept directly linking carbon dose with relative removal of the micropollutant, capacity of the powdered activated carbon was successfully predicted for different initial micropollutant concentrations.","abstract_html":"Many pharmaceuticals have attracted the attention of environmental scientists and are of concern due to their observed occurrence in surface water, ground water, drinking water, sediment, and soil. Further investigations have considered their removal efficiencies in wastewater treatment processes and their ecotoxicological effects. Cytostatics are a class of pharmaceuticals used in the treatment of cancer and have the potential to negatively impact the environment. It is hypothesized that due to their mode of action, practically all eukaryotic organisms are vulnerable to damage, with teratogenicity being the greatest concern at low ng/L levels. This thesis will discuss the contributions to this field in the form of 1) development of a method for chemical analysis of cytostatics in wastewater, 2) occurrence studies, and 3) potential for removal with advanced treatment processes. To expand the knowledge on the environmental occurrence of cytostatics and to compliment a range of cytostatics for which occurrence data are available, a solid phase extraction and HPLC-MS/MS method was established for highly consumed cytostatics 5 fluorouracil, cytarabine, and gemcitabine and the human metabolites uracil 1-beta-d-arabinofuranoside and 2’,2’-difluorodeoxyuridine. Hydrophilic interaction chromatography (HILIC), a chromatography for polar analytes in aqueous samples, was used to achieve a good retention of the polar analytes. Along with the method development, retention mechanisms on the HILIC stationary phase were studied. Both partitioning and adsorption play a role in the retention on the tested sulfoalkylbetaine modified silica HILIC column material. The contribution of these two processes changes over the 1.6-40% range of water in the mobile phase. Although the specific break point is difficult to determine, adsorption becomes more significant as the fraction of water in the mobile phase decreases below approximately 16%. Wastewater from a Swiss hospital was monitored for 5-fluorouracil, gemcitabine and 2’,2’-difluorodeoxyuridine (metabolite of gemcitabine). The limits of quantification were 5.0, 0.9, and 9.0 ng/L and the maximum concentrations detected were 27, 38, and 840 ng/L, respectively. Emission levels within one day and over several days were found to correlate with the pharmacokinetic excretion pattern and the consumed amounts in the hospital during these days. On average, 1.1%, 1.4% and 3.7% of the total excreted amounts of the cytostatics 5 fluorouracil, gemcitabine and 2',2'-difluorodeoxyuridine were found in the hospital wastewater, respectively. Due to low recoveries, stability studies were performed and showed that the half-lives of the analytes in the raw wastewater are very short: 1.0, 0.7 and 2.5 hours, respectively. Environmental impact of 5-fluorouracil, gemcitabine and 2’,2’ difluorodeoxy-uridine seem to be of minor importance, as the environmental risk assessment quotients PEC/PNEC are protective (in orders of magnitude of 10e-3 - 10e-6). Nevertheless, cytostatics are a special group of pharmaceuticals with carcinogenic potency and until data with specific tests and end-points designed especially for this class of pharmaceuticals are available, the precautionary principle should be applied. To study removal possibilities, sorption to powdered activated carbon was investigated. Adsorption is an effective process for the removal of hydrophobic substances from water. Employing it as a wastewater treatment process, polar compounds may also be simultaneously removed to a certain extent. Laboratory scale batch experiments were performed to evaluate the adsorption kinetics and isotherm data of 5-fluorouracil and cytarabine on two powdered activated carbons, Norit SAE Super and Activated Lignite HOK Super. The results of the adsorption characterization were compared with those of two hydrophobic substances, bisphenol A and 17-alpha-ethinylestradiol, produced with the identical experimental conditions and matrix. A dose of 30 mg.L-1 of Norit SAE Super that resulted in removal of the two hydrophobic control compounds below 1% was found to remove 30 and 65% of 5-fluorouracil and cytarabine, respectively. Influence of the solution pH, ionic strength, temperature, and presence of matrix compounds competing for the sorption sites was studied on one of the tested powdered activated carbons, showing that the extent of the competing compounds’ influence is the greatest. Applying a pseudo single-solute isotherm and a concept directly linking carbon dose with relative removal of the micropollutant, capacity of the powdered activated carbon was successfully predicted for different initial micropollutant concentrations.","abstract_has_math":false,"creators":["Koval'ová, L'ubomíra"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Hollender, Juliane"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009","date_published":"2009","updated_at":"2026-07-30T19:40:42Z","subjects":["info:eu-repo/classification/ddc/500","Abwasseranalyse","Abwasserreinigung","Aktivkohle","Antimetabolit","Naturwissenschaften","pharmaceuticals","wastewater","PAC"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114084%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114084%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114084%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/51834","outbound_label":"Repository record","outbound_source":"dc:identifier"},"source_record":{"url":"https://publications.rwth-aachen.de/oai2d?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Apublications.rwth-aachen.de%3A51834","prefix":"oai_dc"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Hollender, Juliane"]},{"key":"dc:creator","label":"Author","values":["Koval'ová, L'ubomíra"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2009"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-32851"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/500","Abwasseranalyse","Abwasserreinigung","Aktivkohle","Antimetabolit","Naturwissenschaften","pharmaceuticals","wastewater","PAC"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/51834","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114084%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Many pharmaceuticals have attracted the attention of environmental scientists and are of concern due to their observed occurrence in surface water, ground water, drinking water, sediment, and soil. Further investigations have considered their removal efficiencies in wastewater treatment processes and their ecotoxicological effects. Cytostatics are a class of pharmaceuticals used in the treatment of cancer and have the potential to negatively impact the environment. It is hypothesized that due to their mode of action, practically all eukaryotic organisms are vulnerable to damage, with teratogenicity being the greatest concern at low ng/L levels. This thesis will discuss the contributions to this field in the form of 1) development of a method for chemical analysis of cytostatics in wastewater, 2) occurrence studies, and 3) potential for removal with advanced treatment processes. To expand the knowledge on the environmental occurrence of cytostatics and to compliment a range of cytostatics for which occurrence data are available, a solid phase extraction and HPLC-MS/MS method was established for highly consumed cytostatics 5 fluorouracil, cytarabine, and gemcitabine and the human metabolites uracil 1-beta-d-arabinofuranoside and 2’,2’-difluorodeoxyuridine. Hydrophilic interaction chromatography (HILIC), a chromatography for polar analytes in aqueous samples, was used to achieve a good retention of the polar analytes. Along with the method development, retention mechanisms on the HILIC stationary phase were studied. Both partitioning and adsorption play a role in the retention on the tested sulfoalkylbetaine modified silica HILIC column material. The contribution of these two processes changes over the 1.6-40% range of water in the mobile phase. Although the specific break point is difficult to determine, adsorption becomes more significant as the fraction of water in the mobile phase decreases below approximately 16%. Wastewater from a Swiss hospital was monitored for 5-fluorouracil, gemcitabine and 2’,2’-difluorodeoxyuridine (metabolite of gemcitabine). The limits of quantification were 5.0, 0.9, and 9.0 ng/L and the maximum concentrations detected were 27, 38, and 840 ng/L, respectively. Emission levels within one day and over several days were found to correlate with the pharmacokinetic excretion pattern and the consumed amounts in the hospital during these days. On average, 1.1%, 1.4% and 3.7% of the total excreted amounts of the cytostatics 5 fluorouracil, gemcitabine and 2',2'-difluorodeoxyuridine were found in the hospital wastewater, respectively. Due to low recoveries, stability studies were performed and showed that the half-lives of the analytes in the raw wastewater are very short: 1.0, 0.7 and 2.5 hours, respectively. Environmental impact of 5-fluorouracil, gemcitabine and 2’,2’ difluorodeoxy-uridine seem to be of minor importance, as the environmental risk assessment quotients PEC/PNEC are protective (in orders of magnitude of 10e-3 - 10e-6). Nevertheless, cytostatics are a special group of pharmaceuticals with carcinogenic potency and until data with specific tests and end-points designed especially for this class of pharmaceuticals are available, the precautionary principle should be applied. To study removal possibilities, sorption to powdered activated carbon was investigated. Adsorption is an effective process for the removal of hydrophobic substances from water. Employing it as a wastewater treatment process, polar compounds may also be simultaneously removed to a certain extent. Laboratory scale batch experiments were performed to evaluate the adsorption kinetics and isotherm data of 5-fluorouracil and cytarabine on two powdered activated carbons, Norit SAE Super and Activated Lignite HOK Super. The results of the adsorption characterization were compared with those of two hydrophobic substances, bisphenol A and 17-alpha-ethinylestradiol, produced with the identical experimental conditions and matrix. A dose of 30 mg.L-1 of Norit SAE Super that resulted in removal of the two hydrophobic control compounds below 1% was found to remove 30 and 65% of 5-fluorouracil and cytarabine, respectively. Influence of the solution pH, ionic strength, temperature, and presence of matrix compounds competing for the sorption sites was studied on one of the tested powdered activated carbons, showing that the extent of the competing compounds’ influence is the greatest. Applying a pseudo single-solute isotherm and a concept directly linking carbon dose with relative removal of the micropollutant, capacity of the powdered activated carbon was successfully predicted for different initial micropollutant concentrations."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University 76 S. : Ill., graph. Darst. (2009). = Aachen, Techn. Hochsch., Diss., 2009"]},{"key":"dc:title","label":"Title","values":["Cytostatics in the aquatic environment : analysis, occurrence, and possibilities for removal"]}]}],"canonical_facts":{"dc:contributor":["Hollender, Juliane"],"dc:coverage":["DE"],"dc:creator":["Koval'ová, L'ubomíra"],"dc:date":["2009"],"dc:description":["Many pharmaceuticals have attracted the attention of environmental scientists and are of concern due to their observed occurrence in surface water, ground water, drinking water, sediment, and soil. Further investigations have considered their removal efficiencies in wastewater treatment processes and their ecotoxicological effects. Cytostatics are a class of pharmaceuticals used in the treatment of cancer and have the potential to negatively impact the environment. It is hypothesized that due to their mode of action, practically all eukaryotic organisms are vulnerable to damage, with teratogenicity being the greatest concern at low ng/L levels. This thesis will discuss the contributions to this field in the form of 1) development of a method for chemical analysis of cytostatics in wastewater, 2) occurrence studies, and 3) potential for removal with advanced treatment processes. To expand the knowledge on the environmental occurrence of cytostatics and to compliment a range of cytostatics for which occurrence data are available, a solid phase extraction and HPLC-MS/MS method was established for highly consumed cytostatics 5 fluorouracil, cytarabine, and gemcitabine and the human metabolites uracil 1-beta-d-arabinofuranoside and 2’,2’-difluorodeoxyuridine. Hydrophilic interaction chromatography (HILIC), a chromatography for polar analytes in aqueous samples, was used to achieve a good retention of the polar analytes. Along with the method development, retention mechanisms on the HILIC stationary phase were studied. Both partitioning and adsorption play a role in the retention on the tested sulfoalkylbetaine modified silica HILIC column material. The contribution of these two processes changes over the 1.6-40% range of water in the mobile phase. Although the specific break point is difficult to determine, adsorption becomes more significant as the fraction of water in the mobile phase decreases below approximately 16%. Wastewater from a Swiss hospital was monitored for 5-fluorouracil, gemcitabine and 2’,2’-difluorodeoxyuridine (metabolite of gemcitabine). The limits of quantification were 5.0, 0.9, and 9.0 ng/L and the maximum concentrations detected were 27, 38, and 840 ng/L, respectively. Emission levels within one day and over several days were found to correlate with the pharmacokinetic excretion pattern and the consumed amounts in the hospital during these days. On average, 1.1%, 1.4% and 3.7% of the total excreted amounts of the cytostatics 5 fluorouracil, gemcitabine and 2',2'-difluorodeoxyuridine were found in the hospital wastewater, respectively. Due to low recoveries, stability studies were performed and showed that the half-lives of the analytes in the raw wastewater are very short: 1.0, 0.7 and 2.5 hours, respectively. Environmental impact of 5-fluorouracil, gemcitabine and 2’,2’ difluorodeoxy-uridine seem to be of minor importance, as the environmental risk assessment quotients PEC/PNEC are protective (in orders of magnitude of 10e-3 - 10e-6). Nevertheless, cytostatics are a special group of pharmaceuticals with carcinogenic potency and until data with specific tests and end-points designed especially for this class of pharmaceuticals are available, the precautionary principle should be applied. To study removal possibilities, sorption to powdered activated carbon was investigated. Adsorption is an effective process for the removal of hydrophobic substances from water. Employing it as a wastewater treatment process, polar compounds may also be simultaneously removed to a certain extent. Laboratory scale batch experiments were performed to evaluate the adsorption kinetics and isotherm data of 5-fluorouracil and cytarabine on two powdered activated carbons, Norit SAE Super and Activated Lignite HOK Super. The results of the adsorption characterization were compared with those of two hydrophobic substances, bisphenol A and 17-alpha-ethinylestradiol, produced with the identical experimental conditions and matrix. A dose of 30 mg.L-1 of Norit SAE Super that resulted in removal of the two hydrophobic control compounds below 1% was found to remove 30 and 65% of 5-fluorouracil and cytarabine, respectively. Influence of the solution pH, ionic strength, temperature, and presence of matrix compounds competing for the sorption sites was studied on one of the tested powdered activated carbons, showing that the extent of the competing compounds’ influence is the greatest. Applying a pseudo single-solute isotherm and a concept directly linking carbon dose with relative removal of the micropollutant, capacity of the powdered activated carbon was successfully predicted for different initial micropollutant concentrations."],"dc:identifier":["https://publications.rwth-aachen.de/record/51834","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-114084%22"],"dc:language":["eng"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-32851"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University 76 S. : Ill., graph. Darst. (2009). = Aachen, Techn. Hochsch., Diss., 2009"],"dc:subject":["info:eu-repo/classification/ddc/500","Abwasseranalyse","Abwasserreinigung","Aktivkohle","Antimetabolit","Naturwissenschaften","pharmaceuticals","wastewater","PAC"],"dc:title":["Cytostatics in the aquatic environment : analysis, occurrence, and possibilities for removal"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:40:42Z"}