Occurrence of the antidiabetic drug Metformin and its ultimate transformation product Guanylurea in several compartments of the aquatic cycle

In 2030, the World Health Organization estimates that more than 350million people will be diagnosed with diabetes. Consequently, Metformin – the biguanide drug of choice orally administered for diabetes type II – is anticipated to see a spike in production. Unlike many pharmaceutical drugs, Metformi...

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Published in:Environment international Vol. 70; pp. 203 - 212
Main Authors: Trautwein, Christoph, Berset, Jean-Daniel, Wolschke, Hendrik, Kümmerer, Klaus
Format: Journal Article
Language:English
Published: Oxford Elsevier Ltd 01.09.2014
Elsevier
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ISSN:0160-4120, 1873-6750, 1873-6750
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Abstract In 2030, the World Health Organization estimates that more than 350million people will be diagnosed with diabetes. Consequently, Metformin – the biguanide drug of choice orally administered for diabetes type II – is anticipated to see a spike in production. Unlike many pharmaceutical drugs, Metformin (Met) is not metabolized by humans but passes through the body unchanged. Entering aquatic compartments, such as in sewage, it can be bacterially transformed to the ultimate transformation product Guanylurea (Gua). Sampling over one week (n=5) from a Southern German sewage treatment plant revealed very high average (AV) concentrations in influent (AVMet=111,800ng/L, AVGua=1300ng/L) and effluent samples (AVMet=4800ng/L, AVGua=44,000ng/L). To provide a more complete picture of the distribution and potential persistence of these compounds in the German water cycle, a new, efficient and highly sensitive liquid chromatography mass spectrometric method with direct injection was used for the measurement of Metformin and Guanylurea in drinking, surface, sewage and seawater. Limits of quantification (LOQ) ranging from 2–10ng/L allowed the detection of Metformin and Guanylurea in different locations such as: Lake Constance (n=11: AVMet=102ng/L, AVGua=16ng/L), river Elbe (n=12: AVMet=472ng/L, AVGua=9ng/L), river Weser (n=6: AVMet=349ng/L, AVGua=137ng/L) and for the first time in marine North Sea water (n=14: AVMet=13ng/L, AVGua=11ng/L). Based on daily water discharges, Metformin loads of 15.2kg/d (Elbe) and 6.4kg/d (Weser) into the North Sea were calculated. Lake Constance is used to abstract potable water which is further purified to be used as drinking water. A first screening of two tap water samples contained 2ng/L and 61ng/L of Metformin, respectively. The results of this study suggest that Metformin and Guanylurea could be distributed over a large fraction of the world's potable water sources and oceans. With no natural degradation processes, these compounds can be easily reintroduced to humans as they enter the food chain. •New HPLC–MS/MS method for Metformin and Guanylurea with minimal LOQs•First detection of both compounds in German rivers Elbe and Weser•First detection in marine environments until 200km North Sea offshore•First detection in multinational Lake Constance and derived drinking water•Absence proof of any efficient degradation process suggests ubiquitous distribution.
AbstractList In 2030, the World Health Organization estimates that more than 350million people will be diagnosed with diabetes. Consequently, Metformin - the biguanide drug of choice orally administered for diabetes type II - is anticipated to see a spike in production. Unlike many pharmaceutical drugs, Metformin (Met) is not metabolized by humans but passes through the body unchanged. Entering aquatic compartments, such as in sewage, it can be bacterially transformed to the ultimate transformation product Guanylurea (Gua). Sampling over one week (n=5) from a Southern German sewage treatment plant revealed very high average (AV) concentrations in influent (AVMet =111,800ng/L, AVGua =1300ng/L) and effluent samples (AVMet =4800ng/L, AVGua =44,000ng/L). To provide a more complete picture of the distribution and potential persistence of these compounds in the German water cycle, a new, efficient and highly sensitive liquid chromatography mass spectrometric method with direct injection was used for the measurement of Metformin and Guanylurea in drinking, surface, sewage and seawater. Limits of quantification (LOQ) ranging from 2-10ng/L allowed the detection of Metformin and Guanylurea in different locations such as: Lake Constance (n=11: AVMet =102ng/L, AVGua =16ng/L), river Elbe (n=12: AVMet =472ng/L, AVGua =9ng/L), river Weser (n=6: AVMet =349ng/L, AVGua =137ng/L) and for the first time in marine North Sea water (n=14: AVMet =13ng/L, AVGua =11ng/L). Based on daily water discharges, Metformin loads of 15.2kg/d (Elbe) and 6.4kg/d (Weser) into the North Sea were calculated. Lake Constance is used to abstract potable water which is further purified to be used as drinking water. A first screening of two tap water samples contained 2ng/L and 61ng/L of Metformin, respectively. The results of this study suggest that Metformin and Guanylurea could be distributed over a large fraction of the world's potable water sources and oceans. With no natural degradation processes, these compounds can be easily reintroduced to humans as they enter the food chain.
In 2030, the World Health Organization estimates that more than 350 million people will be diagnosed with diabetes. Consequently, Metformin - the biguanide drug of choice orally administered for diabetes type II - is anticipated to see a spike in production. Unlike many pharmaceutical drugs, Metformin (Met) is not metabolized by humans but passes through the body unchanged. Entering aquatic compartments, such as in sewage, it can be bacterially transformed to the ultimate transformation product Guanylurea (Gua). Sampling over one week (n=5) from a Southern German sewage treatment plant revealed very high average (AV) concentrations in influent (AVMet=111,800ng/L, AVGua=1300ng/L) and effluent samples (AVMet=4800ng/L, AVGua=44,000ng/L). To provide a more complete picture of the distribution and potential persistence of these compounds in the German water cycle, a new, efficient and highly sensitive liquid chromatography mass spectrometric method with direct injection was used for the measurement of Metformin and Guanylurea in drinking, surface, sewage and seawater. Limits of quantification (LOQ) ranging from 2-10ng/L allowed the detection of Metformin and Guanylurea in different locations such as: Lake Constance (n=11: AVMet=102ng/L, AVGua=16ng/L), river Elbe (n=12: AVMet=472ng/L, AVGua=9ng/L), river Weser (n=6: AVMet=349ng/L, AVGua=137ng/L) and for the first time in marine North Sea water (n=14: AVMet=13ng/L, AVGua=11ng/L). Based on daily water discharges, Metformin loads of 15.2kg/d (Elbe) and 6.4kg/d (Weser) into the North Sea were calculated. Lake Constance is used to abstract potable water which is further purified to be used as drinking water. A first screening of two tap water samples contained 2ng/L and 61ng/L of Metformin, respectively. The results of this study suggest that Metformin and Guanylurea could be distributed over a large fraction of the world's potable water sources and oceans. With no natural degradation processes, these compounds can be easily reintroduced to humans as they enter the food chain.In 2030, the World Health Organization estimates that more than 350 million people will be diagnosed with diabetes. Consequently, Metformin - the biguanide drug of choice orally administered for diabetes type II - is anticipated to see a spike in production. Unlike many pharmaceutical drugs, Metformin (Met) is not metabolized by humans but passes through the body unchanged. Entering aquatic compartments, such as in sewage, it can be bacterially transformed to the ultimate transformation product Guanylurea (Gua). Sampling over one week (n=5) from a Southern German sewage treatment plant revealed very high average (AV) concentrations in influent (AVMet=111,800ng/L, AVGua=1300ng/L) and effluent samples (AVMet=4800ng/L, AVGua=44,000ng/L). To provide a more complete picture of the distribution and potential persistence of these compounds in the German water cycle, a new, efficient and highly sensitive liquid chromatography mass spectrometric method with direct injection was used for the measurement of Metformin and Guanylurea in drinking, surface, sewage and seawater. Limits of quantification (LOQ) ranging from 2-10ng/L allowed the detection of Metformin and Guanylurea in different locations such as: Lake Constance (n=11: AVMet=102ng/L, AVGua=16ng/L), river Elbe (n=12: AVMet=472ng/L, AVGua=9ng/L), river Weser (n=6: AVMet=349ng/L, AVGua=137ng/L) and for the first time in marine North Sea water (n=14: AVMet=13ng/L, AVGua=11ng/L). Based on daily water discharges, Metformin loads of 15.2kg/d (Elbe) and 6.4kg/d (Weser) into the North Sea were calculated. Lake Constance is used to abstract potable water which is further purified to be used as drinking water. A first screening of two tap water samples contained 2ng/L and 61ng/L of Metformin, respectively. The results of this study suggest that Metformin and Guanylurea could be distributed over a large fraction of the world's potable water sources and oceans. With no natural degradation processes, these compounds can be easily reintroduced to humans as they enter the food chain.
In 2030, the World Health Organization estimates that more than 350million people will be diagnosed with diabetes. Consequently, Metformin – the biguanide drug of choice orally administered for diabetes type II – is anticipated to see a spike in production. Unlike many pharmaceutical drugs, Metformin (Met) is not metabolized by humans but passes through the body unchanged. Entering aquatic compartments, such as in sewage, it can be bacterially transformed to the ultimate transformation product Guanylurea (Gua). Sampling over one week (n=5) from a Southern German sewage treatment plant revealed very high average (AV) concentrations in influent (AVMet=111,800ng/L, AVGua=1300ng/L) and effluent samples (AVMet=4800ng/L, AVGua=44,000ng/L). To provide a more complete picture of the distribution and potential persistence of these compounds in the German water cycle, a new, efficient and highly sensitive liquid chromatography mass spectrometric method with direct injection was used for the measurement of Metformin and Guanylurea in drinking, surface, sewage and seawater. Limits of quantification (LOQ) ranging from 2–10ng/L allowed the detection of Metformin and Guanylurea in different locations such as: Lake Constance (n=11: AVMet=102ng/L, AVGua=16ng/L), river Elbe (n=12: AVMet=472ng/L, AVGua=9ng/L), river Weser (n=6: AVMet=349ng/L, AVGua=137ng/L) and for the first time in marine North Sea water (n=14: AVMet=13ng/L, AVGua=11ng/L). Based on daily water discharges, Metformin loads of 15.2kg/d (Elbe) and 6.4kg/d (Weser) into the North Sea were calculated. Lake Constance is used to abstract potable water which is further purified to be used as drinking water. A first screening of two tap water samples contained 2ng/L and 61ng/L of Metformin, respectively. The results of this study suggest that Metformin and Guanylurea could be distributed over a large fraction of the world's potable water sources and oceans. With no natural degradation processes, these compounds can be easily reintroduced to humans as they enter the food chain. •New HPLC–MS/MS method for Metformin and Guanylurea with minimal LOQs•First detection of both compounds in German rivers Elbe and Weser•First detection in marine environments until 200km North Sea offshore•First detection in multinational Lake Constance and derived drinking water•Absence proof of any efficient degradation process suggests ubiquitous distribution.
In 2030, the World Health Organization estimates that more than 350 million people will be diagnosed with diabetes. Consequently, Metformin - the biguanide drug of choice orally administered for diabetes type II - is anticipated to see a spike in production. Unlike many pharmaceutical drugs, Metformin (Met) is not metabolized by humans but passes through the body unchanged. Entering aquatic compartments, such as in sewage, it can be bacterially transformed to the ultimate transformation product Guanylurea (Gua). Sampling over one week (n=5) from a Southern German sewage treatment plant revealed very high average (AV) concentrations in influent (AVMet=111,800ng/L, AVGua=1300ng/L) and effluent samples (AVMet=4800ng/L, AVGua=44,000ng/L). To provide a more complete picture of the distribution and potential persistence of these compounds in the German water cycle, a new, efficient and highly sensitive liquid chromatography mass spectrometric method with direct injection was used for the measurement of Metformin and Guanylurea in drinking, surface, sewage and seawater. Limits of quantification (LOQ) ranging from 2-10ng/L allowed the detection of Metformin and Guanylurea in different locations such as: Lake Constance (n=11: AVMet=102ng/L, AVGua=16ng/L), river Elbe (n=12: AVMet=472ng/L, AVGua=9ng/L), river Weser (n=6: AVMet=349ng/L, AVGua=137ng/L) and for the first time in marine North Sea water (n=14: AVMet=13ng/L, AVGua=11ng/L). Based on daily water discharges, Metformin loads of 15.2kg/d (Elbe) and 6.4kg/d (Weser) into the North Sea were calculated. Lake Constance is used to abstract potable water which is further purified to be used as drinking water. A first screening of two tap water samples contained 2ng/L and 61ng/L of Metformin, respectively. The results of this study suggest that Metformin and Guanylurea could be distributed over a large fraction of the world's potable water sources and oceans. With no natural degradation processes, these compounds can be easily reintroduced to humans as they enter the food chain.
Author Kümmerer, Klaus
Trautwein, Christoph
Wolschke, Hendrik
Berset, Jean-Daniel
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  surname: Wolschke
  fullname: Wolschke, Hendrik
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  organization: Sustainable Chemistry and Material Resources, Institute of Environmental Chemistry, Faculty of Sustainability, Leuphana University Lüneburg, Scharnhorststrasse 1, D-21335 Lüneburg, Germany
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  organization: Sustainable Chemistry and Material Resources, Institute of Environmental Chemistry, Faculty of Sustainability, Leuphana University Lüneburg, Scharnhorststrasse 1, D-21335 Lüneburg, Germany
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ID FETCH-LOGICAL-c491t-797aadddf35cf58a4f46f0586b25e081e6dba8d99e385666b505da5ce2c9da0a3
ISICitedReferencesCount 134
ISICitedReferencesURI http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000339693200020&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D
ISSN 0160-4120
1873-6750
IngestDate Sun Sep 28 02:38:09 EDT 2025
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IsPeerReviewed true
IsScholarly true
Keywords Drinking water
Pollution
Emerging contaminants
Waste water
Seawater
Pharmaceuticals
Drug
Transformation
Pollutant behavior
Metabolite
Cycle
Trophic chain
Hypoglycemic agent
Water pollution
Metformin
Contaminant
Public health
Chemical contamination
Language English
License CC BY 4.0
Copyright © 2014 Elsevier Ltd. All rights reserved.
LinkModel OpenURL
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content type line 23
PMID 24954924
PQID 1543685495
PQPubID 23479
PageCount 10
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proquest_miscellaneous_1642286247
proquest_miscellaneous_1627980118
proquest_miscellaneous_1543685495
pubmed_primary_24954924
pascalfrancis_primary_28605508
crossref_primary_10_1016_j_envint_2014_05_008
crossref_citationtrail_10_1016_j_envint_2014_05_008
elsevier_sciencedirect_doi_10_1016_j_envint_2014_05_008
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PublicationTitle Environment international
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Elsevier
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Snippet In 2030, the World Health Organization estimates that more than 350million people will be diagnosed with diabetes. Consequently, Metformin – the biguanide drug...
In 2030, the World Health Organization estimates that more than 350 million people will be diagnosed with diabetes. Consequently, Metformin - the biguanide...
In 2030, the World Health Organization estimates that more than 350million people will be diagnosed with diabetes. Consequently, Metformin - the biguanide drug...
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SubjectTerms Animal, plant and microbial ecology
Applied ecology
Applied sciences
Bacteria
Bacteria - metabolism
Biological and medical sciences
Biotransformation
drinking
Drinking water
Drinking Water - analysis
Drinking Water - microbiology
Drugs
Ecotoxicology, biological effects of pollution
Emerging contaminants
Environmental Monitoring
Environmental pollutants toxicology
Exact sciences and technology
food chain
Fresh water environment
Fundamental and applied biological sciences. Psychology
humans
hydrologic cycle
Hypoglycemic Agents - analysis
Hypoglycemic Agents - metabolism
Kinetics
Lake Constance
Lakes
liquid chromatography
Marine and brackish environment
mass spectrometry
Medical sciences
Metformin
Metformin - analysis
Metformin - metabolism
Natural water pollution
noninsulin-dependent diabetes mellitus
North Sea
oceans
oral administration
people
Pharmaceuticals
Pollution
Rivers
Rivers - chemistry
Rivers - microbiology
screening
Seawater
sewage
Sewage - chemistry
Sewage - microbiology
sewage treatment
tap water
Thiourea - analysis
Toxicology
Transformations
Waste water
Water
Water Pollutants, Chemical - analysis
Water Pollutants, Chemical - metabolism
Water treatment and pollution
World Health Organization
Title Occurrence of the antidiabetic drug Metformin and its ultimate transformation product Guanylurea in several compartments of the aquatic cycle
URI https://dx.doi.org/10.1016/j.envint.2014.05.008
https://www.ncbi.nlm.nih.gov/pubmed/24954924
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Volume 70
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