Identification of phototransformation products of the antiepileptic drug gabapentin: Biodegradability and initial assessment of toxicity.
The anticonvulsant drug Gabapentin (GAB) is used for the treatment of various diseases (e.g. epilepsy, bipolar disorder, neuropathic pain) and is being consumed in high amounts. As GAB is not metabolized and shows a weak elimination in sewage treatment plants (STPs), it has been detected in surface water and even in raw potable water. Moreover, the confirmed teratogenic effects of GAB indicate the need for further investigations regarding options for the elimination of GAB in the water cycle. Little is known about the behavior of GAB during treatment with UV light, which is normally used for the disinfection of potable water and discussed for advanced wastewater treatment. In this study, GAB was exposed to polychromatic UV irradiation at different initial concentrations in aqueous solution. Afterwards the structures of the resulting phototransformation products (PTPs) were identified and elucidated by means of high-resolution mass spectrometry. GAB and photolytic mixtures were submitted to the Closed Bottle Test (CBT; OECD 301 D) to assess biodegradability. Furthermore, the toxicity of GAB and its photolytic mixtures was initially addressed on screening level using a modified luminescent bacteria test (LBT) and the umu-test (ISO/FDIS 13829). Environmentally realistic concentrations of GAB were disclosed by predicting STP influent concentrations (24.3 and 23.2 μg L(-1)). GAB with initial concentration of 100 mg L(-1) was eliminated by 80% after 128 min of direct UV irradiation, but just 9% of non-purgeable organic carbon (NPOC) was removed indicating the formation of dead-end transformation products (TPs). Structures of different PTPs were elucidated and several identical PTPs could also be identified at lower initial treatment concentrations (20 mg L(-1), 5 mg L(-1), 1 mg L(-1) and 0.1 mg L(-1)). GAB was classified as not readily biodegradable. Moreover, photo treatment did not result in better biodegradable PTPs. With increasing UV treatment duration, photolytic mixtures of GAB showed an increased inhibition of both, the bacterial luminescence emission as well as the growth in the modified LBT. In the umu-test no significant induction of the umuC gene as an indicator of genotoxicity was observed. Our results show that UV irradiation of GAB containing water would lead to the formation of recalcitrant PTPs. Considering that GAB was found in raw drinking water, the formation of toxic PTPs during drinking water treatment with UV light might be possible. Therefore, further studies should be conducted regarding the fate and effects on human health and the environment of GAB and the PTPs identified within this study.
Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, C13, Scharnhorstrasse 1, DE-21335 Lüneburg, Germany; Hospital Pharmacy, Ortenau Klinikum Offenburg-Gengenbach, Ebertplatz 12, DE-77654 Offenburg, Germany. Electronic address: manuel.herrmann@leuphana.de.
Manuel
M
Herrmann
Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, C13, Scharnhorstrasse 1, DE-21335 Lüneburg, Germany. Electronic address: jakob.menz@leuphana.de.
Jakob
J
Menz
Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, C13, Scharnhorstrasse 1, DE-21335 Lüneburg, Germany. Electronic address: oliver.olsson@leuphana.de.
Oliver
O
Olsson
Sustainable Chemistry and Material Resources, Institute of Sustainable and Environmental Chemistry, Leuphana University of Lüneburg, C13, Scharnhorstrasse 1, DE-21335 Lüneburg, Germany. Electronic address: klaus.kuemmerer@leuphana.de.
Klaus
K
Kümmerer
D000588:Amines / Q000528:radiation effects* / Q000633:toxicity; D000927:Anticonvulsants / Q000528:radiation effects* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D001673:Biodegradation, Environmental; D003509:Cyclohexanecarboxylic Acids / Q000528:radiation effects* / Q000633:toxicity; D000077206:Gabapentin; D049449:Luminescence; D009152:Mutagenicity Tests; D010782:Photolysis; D023382:Toxicity Tests, Acute / Q000379:methods; D014466:Ultraviolet Rays; D014874:Water Pollutants, Chemical / Q000528:radiation effects* / Q000633:toxicity; D005680:gamma-Aminobutyric Acid / Q000528:radiation effects* / Q000633:toxicity
D000588:Amines; D000927:Anticonvulsants; D003509:Cyclohexanecarboxylic Acids; D014874:Water Pollutants, Chemical; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin
Closed Bottle Test (CBT); High-resolution mass spectrometry; Luminescent bacteria test; UV photolysis; Umu-test