TY - JOUR

T1 - Aerobic Biodegradability of the Calcium Channel Antagonist Verapamil and Identification of a Microbial Dead-End Transformation Product Studied by LC-MS/MS

AU - Trautwein, Christoph

AU - Kümmerer, Klaus

AU - Metzger, Jörg W.

N1 - Funding Information: The authors wish to thank Armin Koenig and Andreas Laengin (Department of Environmental Health Sciences) for their help with the experiments. The authors wish to thank especially Abbott Laboratories for providing the verapamil metabolites D617, D620 and norverapamil to verify the structure of the found dead-end transformation product. This work was supported through Badenova AG, Freiburg, by partial funding of the experimental programme.

PY - 2008/6/1

Y1 - 2008/6/1

N2 - In recent years pharmaceuticals and personal care products have been detected in increasing concentrations in hospital effluents, sewage treatment plants (STP) as well as in different environmental compartments such as surface water, groundwater and soil. Little is known about the elimination of these substances during sewage treatment or about the formation of potential metabolites in the environment caused by bacterial biotransformation. To assess the biodegradability of the popular cardiovascular drug verapamil and the possible formation of potential microbial degradation products, two tests from the OECD series were used in the present study: the widely used Closed Bottle test (OECD 301 D) and the modified Zahn-Wellens test (OECD 302 B). In the Closed Bottle test, a screening test that simulates the conditions of an environmental surface water compartment, no biological degradation was observed for verapamil at concentrations of 2.33mgl(-1). In the Zahn-Wellens test, a test for inherent biodegradability which allows evaluation of aerobic degradation at high bacterial density, only a partial biological degradation was found. Analysis of test samples by high performance liquid chromatography coupled to multiple stage mass spectrometry (HPLC-MS(n)) revealed 2-(3,4-dimethoxyphenyl)-2-isopropyl-5-(methylamino)pentane nitrile, already known as D617 (Knoll nomenclature), a metabolite of mammalian metabolism, which is the major degradation product and dead-end transformation product of aerobic degradation of verapamil

AB - In recent years pharmaceuticals and personal care products have been detected in increasing concentrations in hospital effluents, sewage treatment plants (STP) as well as in different environmental compartments such as surface water, groundwater and soil. Little is known about the elimination of these substances during sewage treatment or about the formation of potential metabolites in the environment caused by bacterial biotransformation. To assess the biodegradability of the popular cardiovascular drug verapamil and the possible formation of potential microbial degradation products, two tests from the OECD series were used in the present study: the widely used Closed Bottle test (OECD 301 D) and the modified Zahn-Wellens test (OECD 302 B). In the Closed Bottle test, a screening test that simulates the conditions of an environmental surface water compartment, no biological degradation was observed for verapamil at concentrations of 2.33mgl(-1). In the Zahn-Wellens test, a test for inherent biodegradability which allows evaluation of aerobic degradation at high bacterial density, only a partial biological degradation was found. Analysis of test samples by high performance liquid chromatography coupled to multiple stage mass spectrometry (HPLC-MS(n)) revealed 2-(3,4-dimethoxyphenyl)-2-isopropyl-5-(methylamino)pentane nitrile, already known as D617 (Knoll nomenclature), a metabolite of mammalian metabolism, which is the major degradation product and dead-end transformation product of aerobic degradation of verapamil

KW - Closed Bottle Test

KW - Zahn-Wellens Test

KW - Biodegradation

KW - Bacterial metabolism

KW - Dead-end metabolite

KW - D617

KW - Verapamil

KW - Chemistry

UR - http://www.scopus.com/inward/record.url?scp=43649091385&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/5354ccf1-8175-32e1-a147-bcf789422b71/

U2 - 10.1016/j.chemosphere.2008.02.022

DO - 10.1016/j.chemosphere.2008.02.022

M3 - Journal articles

VL - 72

SP - 442

EP - 450

JO - Chemosphere

JF - Chemosphere

SN - 0045-6535

IS - 3

ER -