Degradation of duloxetine: Identification of transformation products by UHPLC-ESI(+)-HRMS/MS,in silico toxicity and wastewater analysis
|
摘要
Duloxetine(DUL), an antidepressant drug, has been detected in surface water and wastewater effluents, however, there is little information on the formation of its transformation products(TPs). In this work, hydrolysis, photodegradation(UV irradiation) and chlorination experiments were performed on spiked distillated water, under controlled experimental conditions to simulate abiotic processes that can occur in the environment and wastewater treatment plants(WWTPs). Eleven TPs, nine from reaction with UV light and two from chlorine contact, were formed and detected by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, and nine of them had their chemical structures elucidated upon analyses of their fragmentation patterns in MS/MS spectra. The formation and degradation of the TPs were observed. The parent compound was completely degraded after30 min in photodegradation and after 24 hr in chlorination. Almost all TPs were completely degraded in the experiments. The ecotoxicity and mutagenicity of the TPs were predicted based on several in silico models and it was found that a few of these products presented more ecotoxicity than DUL itself and six TPs showed positive mutagenicity. Finally, wastewater samples were analyzed and DUL and one TP, possibly formed by chlorination process, were detected in the effluent, which showed that WWTP not only did not remove DUL, but also formed a TP.
Duloxetine(DUL), an antidepressant drug, has been detected in surface water and wastewater effluents, however, there is little information on the formation of its transformation products(TPs). In this work, hydrolysis, photodegradation(UV irradiation) and chlorination experiments were performed on spiked distillated water, under controlled experimental conditions to simulate abiotic processes that can occur in the environment and wastewater treatment plants(WWTPs). Eleven TPs, nine from reaction with UV light and two from chlorine contact, were formed and detected by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, and nine of them had their chemical structures elucidated upon analyses of their fragmentation patterns in MS/MS spectra. The formation and degradation of the TPs were observed. The parent compound was completely degraded after30 min in photodegradation and after 24 hr in chlorination. Almost all TPs were completely degraded in the experiments. The ecotoxicity and mutagenicity of the TPs were predicted based on several in silico models and it was found that a few of these products presented more ecotoxicity than DUL itself and six TPs showed positive mutagenicity. Finally, wastewater samples were analyzed and DUL and one TP, possibly formed by chlorination process, were detected in the effluent, which showed that WWTP not only did not remove DUL, but also formed a TP.
Duloxetine(DUL), an antidepressant drug, has been detected in surface water and wastewater effluents, however, there is little information on the formation of its transformation products(TPs). In this work, hydrolysis, photodegradation(UV irradiation) and chlorination experiments were performed on spiked distillated water, under controlled experimental conditions to simulate abiotic processes that can occur in the environment and wastewater treatment plants(WWTPs). Eleven TPs, nine from reaction with UV light and two from chlorine contact, were formed and detected by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry, and nine of them had their chemical structures elucidated upon analyses of their fragmentation patterns in MS/MS spectra. The formation and degradation of the TPs were observed. The parent compound was completely degraded after30 min in photodegradation and after 24 hr in chlorination. Almost all TPs were completely degraded in the experiments. The ecotoxicity and mutagenicity of the TPs were predicted based on several in silico models and it was found that a few of these products presented more ecotoxicity than DUL itself and six TPs showed positive mutagenicity. Finally, wastewater samples were analyzed and DUL and one TP, possibly formed by chlorination process, were detected in the effluent, which showed that WWTP not only did not remove DUL, but also formed a TP.
引文
Acu?a,V.,Ginebreda,A.,Mor,J.R.,Petrovic,M.,Sabater,S.,Sumpter,J.,et al.,2015.Balancing the health benefits and environmental risks of pharmaceuticals:diclofenac as an example.Environ.Int.85,327-333.
Beretsou,V.G.,Psoma,A.K.,Gago-Ferrero,P.,Aalizadeh,R.,Fenner,K.,Thomaidis,N.S.,2016.Identification of biotransformation products of citalopram formed in activated sludge.Water Res.103,205-214.
Bletsou,A.A.,Jeon,J.,Hollender,J.,Archontaki,E.,Thomaidis,N.S.,2015.Targeted and non-targeted liquid chromatography-mass spectrometric workflows for identification of transformation products of emerging pollutants in the aquatic environment.TrAC Trends Anal.Chem.66,32-44.
Carpinteiro,I.,Rodil,R.,Quintana,J.B.,Cela,R.,2017.Reaction of diazepam and related benzodiazepines with chlorine.Kinetics,transformation products and in-silico toxicological assessment.Water Res.120,280-289.
Chadha,R.,Bali,A.,Bansal,G.,2016.Characterization of stress degradation products of duloxetine hydrochloride employing LC-UV/PDA and LC-MS/TOF studies.J.Pharm.Biomed.Anal.121,39-55.
Chhalotiya,U.K.,Bhatt,K.K.,Shah,D.A.,Baldania,S.L.,2010.Development and validation of a stability-indicating RP-HPLCmethod for duloxetine hydrochloride in its bulk and tablet dosage form.Sci.Pharm.78(4),857-868.
Datar,P.A.,Waghmare,R.U.,2014.Development and validation of an analytical method for the stability of duloxetine hydrochloride.J.Taibah.Univ.Sci.8(4),357-363.
DGS(Directorate-General of Health),2016.A Saúde dos Portugueses.Dire??o de Servi?os de Informa??o e Análise.Portugal.Available at.https://comum.rcaap.pt/bitstream/10400.26/18278/1/A%20Sa%C3%BAde%20dos%20Portugueses%202016.pdf(Accessed September 09,2018).
Di Poi,C.,Evariste,L.,Serpentini,A.,Halm-Lemeille,M.P.,Lebel,J.M.,Costil,K.,2014.Toxicity of five antidepressant drugs on embryo-larval development and metamorphosis success in the Pacific oyster,Crassostrea gigas.Environ.Sci.Pollut.Res.Int.21(23),13302-13314.
Directive,2013.Directive 2013/39/EU of the European Parliament and of the Council of 12 August 2013 amending Directives 2000/60/EC and 2008/105/EC as regards priority substances in the field of water policy.Off.J.Eur.Union 226,1-17/39/EU.,2013.
El Najjar,N.H.,Deborde,M.,Journel,R.,Vel Leitner,N.K.,2013.Aqueous chlorination of levofloxacin:kinetic and mechanistic study,transformation product identification and toxicity.Water Res.47(1),121-129.
Fick,J.,Lindberg,R.H.,Kaj,L.,Brorstr?m-Lundén,E.,2011.Results from the Swedish National Screening Programme 2010.Subreport 3.Pharmaceuticals.Swedish Environmental Research Institute,p.56 IVL Report B2014.
Johnson,P.S.,Cook,P.L.,Liu,X.,Yang,W.,Bai,Y.,Abbott,N.L.,et al.,2011.Universal mechanism for breaking amide bonds by ionizing radiation.J.Chem.Phys.135,44702-44709.
Kumar,N.,Sangeetha,D.,Vaghela,B.,Reddy,P.S.,Raghav,A.,2012.Development and validation of a stability indicating RP-LCmethod for the estimation of process related impurities and degradation products of duloxetine hydrochloride and phthalic acid in duloxetine hydrochloride delayed release capsules.J.Liq.Chromatogr.Relat.Technol.35(7),867-881.
Mcconkey,B.J.,Hewitt,L.M.,Dixon,D.G.,Greenberg,B.M.,2002.Natural sunlight induced photooxidation of naphthalene in aqueous solution.Water Air Soil Pollut.136(1-4),347-359.
Minguez,L.,Pedelucq,J.,Farcy,E.,Ballandonne,C.,Budzinski,H.,Halm-Lemeille,M.P.,2016.Toxicities of 48 pharmaceuticals and their freshwater and marine environmental assessment in northwestern France.Environ.Sci.Pollut.Res.23(6),4992-5001.
Pinto da Costa,J.,Gir?o,A.V.,Monteiro,O.C.,Trindade,T.,Costa,M.C.,2015.Biotechnologically obtained nanocomposites:a practical application for photodegradation of safranin-T under UV-vis and solar light.J.Environ.Sci.Health A Tox.Hazard.Subst.Environ.Eng.50(10),996-1010.
Santoke,H.,Song,W.,Cooper,W.J.,Peake,B.M.,2012.Advanced oxidation treatment and photochemical fate of selected antidepressant pharmaceuticals in solutions of Suwannee River humic acid.J.Hazard.Mater.217-218,382-390.
Schultz,M.M.,Furlong,E.T.,2008.Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS.Anal.Chem.80(5),1756-1762.
Silva,L.J.G.,Pereira,A.M.P.T.,Meisel,L.M.,Lino,C.M.,Pena,A.,2015.Reviewing the serotonin reuptake inhibitors(SSRIs)footprint in the aquatic biota:uptake,bioaccumulation and ecotoxicology.Environ.Pollut.197,127-143.
Sinha,V.R.,Anamika,Kumria,R.,Bhinge,J.R.,2009.Stress degradation studies on duloxetine hydrochloride and development of an RP-HPLC method for its determination in capsule formulation.J.Chromatogr.Sci.47(7),589-593.
Sorrell,T.M.(Ed.),2005.Organic Chemistry,second ed.University Science Books,California.
Subedi,B.,Kannan,K.,2015.Occurrence and fate of select psychoactive pharmaceuticals and antihypertensives in two wastewater treatment plants in New York State,USA.Sci.Total Environ.514,273-280.
Taylor,D.,Senac,T.,2014.Human pharmaceutical products in the environment-the“problem”in perspective.Chemosphere115,95-99.
Trawiński,J.,Skibiński,R.,2017.Photolytic and photocatalytic degradation of tandospirone:determination of kinetics,identification of transformation products and in silico estimation of toxicity.Sci.Total Environ.591,775-798.
US EPA(United States Environmental Protection Agency),2016.User's Guide for T.E.S.T.(Toxicity Estimation Software Tool):AProgram to Estimate Toxicity from Molecular Structure.version 4.2.Available at.www.epa.gov/sites/production/files/2016-05/documents/600r16058.pdf,Accessed date:20 October2018.
US EPA(United States Environmental Protection Agency),2017a.The third unregulated contaminant monitoring rule(UCMR3):Data summary,January 2017.EPA 815-S-17-001.Office of Water(MS-140).
US EPA(United States Environmental Protection Agency),2017b.Methodology document for the ECOlogical Structure-Activity Relationship Model(ECOSAR)Class Program(Ecological Structure Activity Relationships).version 2.0.Available at.www.epa.gov/tsca-screening-tools/ecological-structure-activity-relationships-program-ecosar-methodology-document,Accessed date:15 October 2018.
Vinu,R.,Madras,G.,2011.Photocatalytic degradation of water pollutants using nano-TiO2.Energy efficiency and renewable energy through nanotechnology.In:Zang,L.(Ed.),Green Energy and Technology.Springer,London,pp.626-677.
Wang,W.L.,Wu,Q.Y.,Huang,N.,Wang,T.,Hu,H.Y.,2016.Synergistic effect between UV and chlorine(UV/chlorine)on the degradation of carbamazepine:influence factors and radical species.Water Res.98,190-198.
Wilde,M.L.,Menz,J.,Trautwein,C.,Leder,C.,Kümmerer,K.,2016.Environmental fate and effect assessment of thioridazine and its transformation products formed by photodegradation.Environ.Pollut.213,658-670.
Worth,A.P.,van Leeuwen,C.J.,Hartung,T.,2004.The prospects for using(Q)SARs in a changing political environment:high expectations and a key role for the Commission's Joint Research Centre.SAR QSAR Environ.Res.15(5-6),331-343.
Writer,J.H.,Ferrer,I.,Barber,L.B.,Thurman,E.M.,2013.Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters.Sci.Total Environ.461-462,519-527.
Yin,J.,Niu,Y.,Shao,B.,2017.Products of methotrexate during chlorination.J.Environ.Sci.55,100-108.
Yuzawa,H.,Aoki,M.,Otake,K.,Hattori,T.,Itoh,H.,Yoshida,H.,2012.Reaction mechanism of aromatic ring hydroxylation by water over platinum-loaded titanium oxide photocatalyst.J.Phys.Chem.C 116(48),25376-25387.
Zhou,S.,Xia,Y.,Li,T.,Yao,T.,Shi,Z.,Zhu,S.,et al.,2016.Degradation of carbamazepine by UV/chlorine advanced oxidation process and formation of disinfection by-products.Environ.Sci.Pollut.Res.23(16),16448-16455.
Beretsou,V.G.,Psoma,A.K.,Gago-Ferrero,P.,Aalizadeh,R.,Fenner,K.,Thomaidis,N.S.,2016.Identification of biotransformation products of citalopram formed in activated sludge.Water Res.103,205-214.
Bletsou,A.A.,Jeon,J.,Hollender,J.,Archontaki,E.,Thomaidis,N.S.,2015.Targeted and non-targeted liquid chromatography-mass spectrometric workflows for identification of transformation products of emerging pollutants in the aquatic environment.TrAC Trends Anal.Chem.66,32-44.
Carpinteiro,I.,Rodil,R.,Quintana,J.B.,Cela,R.,2017.Reaction of diazepam and related benzodiazepines with chlorine.Kinetics,transformation products and in-silico toxicological assessment.Water Res.120,280-289.
Chadha,R.,Bali,A.,Bansal,G.,2016.Characterization of stress degradation products of duloxetine hydrochloride employing LC-UV/PDA and LC-MS/TOF studies.J.Pharm.Biomed.Anal.121,39-55.
Chhalotiya,U.K.,Bhatt,K.K.,Shah,D.A.,Baldania,S.L.,2010.Development and validation of a stability-indicating RP-HPLCmethod for duloxetine hydrochloride in its bulk and tablet dosage form.Sci.Pharm.78(4),857-868.
Datar,P.A.,Waghmare,R.U.,2014.Development and validation of an analytical method for the stability of duloxetine hydrochloride.J.Taibah.Univ.Sci.8(4),357-363.
DGS(Directorate-General of Health),2016.A Saúde dos Portugueses.Dire??o de Servi?os de Informa??o e Análise.Portugal.Available at.https://comum.rcaap.pt/bitstream/10400.26/18278/1/A%20Sa%C3%BAde%20dos%20Portugueses%202016.pdf(Accessed September 09,2018).
Di Poi,C.,Evariste,L.,Serpentini,A.,Halm-Lemeille,M.P.,Lebel,J.M.,Costil,K.,2014.Toxicity of five antidepressant drugs on embryo-larval development and metamorphosis success in the Pacific oyster,Crassostrea gigas.Environ.Sci.Pollut.Res.Int.21(23),13302-13314.
Directive,2013.Directive 2013/39/EU of the European Parliament and of the Council of 12 August 2013 amending Directives 2000/60/EC and 2008/105/EC as regards priority substances in the field of water policy.Off.J.Eur.Union 226,1-17/39/EU.,2013.
El Najjar,N.H.,Deborde,M.,Journel,R.,Vel Leitner,N.K.,2013.Aqueous chlorination of levofloxacin:kinetic and mechanistic study,transformation product identification and toxicity.Water Res.47(1),121-129.
Fick,J.,Lindberg,R.H.,Kaj,L.,Brorstr?m-Lundén,E.,2011.Results from the Swedish National Screening Programme 2010.Subreport 3.Pharmaceuticals.Swedish Environmental Research Institute,p.56 IVL Report B2014.
Johnson,P.S.,Cook,P.L.,Liu,X.,Yang,W.,Bai,Y.,Abbott,N.L.,et al.,2011.Universal mechanism for breaking amide bonds by ionizing radiation.J.Chem.Phys.135,44702-44709.
Kumar,N.,Sangeetha,D.,Vaghela,B.,Reddy,P.S.,Raghav,A.,2012.Development and validation of a stability indicating RP-LCmethod for the estimation of process related impurities and degradation products of duloxetine hydrochloride and phthalic acid in duloxetine hydrochloride delayed release capsules.J.Liq.Chromatogr.Relat.Technol.35(7),867-881.
Mcconkey,B.J.,Hewitt,L.M.,Dixon,D.G.,Greenberg,B.M.,2002.Natural sunlight induced photooxidation of naphthalene in aqueous solution.Water Air Soil Pollut.136(1-4),347-359.
Minguez,L.,Pedelucq,J.,Farcy,E.,Ballandonne,C.,Budzinski,H.,Halm-Lemeille,M.P.,2016.Toxicities of 48 pharmaceuticals and their freshwater and marine environmental assessment in northwestern France.Environ.Sci.Pollut.Res.23(6),4992-5001.
Pinto da Costa,J.,Gir?o,A.V.,Monteiro,O.C.,Trindade,T.,Costa,M.C.,2015.Biotechnologically obtained nanocomposites:a practical application for photodegradation of safranin-T under UV-vis and solar light.J.Environ.Sci.Health A Tox.Hazard.Subst.Environ.Eng.50(10),996-1010.
Santoke,H.,Song,W.,Cooper,W.J.,Peake,B.M.,2012.Advanced oxidation treatment and photochemical fate of selected antidepressant pharmaceuticals in solutions of Suwannee River humic acid.J.Hazard.Mater.217-218,382-390.
Schultz,M.M.,Furlong,E.T.,2008.Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS.Anal.Chem.80(5),1756-1762.
Silva,L.J.G.,Pereira,A.M.P.T.,Meisel,L.M.,Lino,C.M.,Pena,A.,2015.Reviewing the serotonin reuptake inhibitors(SSRIs)footprint in the aquatic biota:uptake,bioaccumulation and ecotoxicology.Environ.Pollut.197,127-143.
Sinha,V.R.,Anamika,Kumria,R.,Bhinge,J.R.,2009.Stress degradation studies on duloxetine hydrochloride and development of an RP-HPLC method for its determination in capsule formulation.J.Chromatogr.Sci.47(7),589-593.
Sorrell,T.M.(Ed.),2005.Organic Chemistry,second ed.University Science Books,California.
Subedi,B.,Kannan,K.,2015.Occurrence and fate of select psychoactive pharmaceuticals and antihypertensives in two wastewater treatment plants in New York State,USA.Sci.Total Environ.514,273-280.
Taylor,D.,Senac,T.,2014.Human pharmaceutical products in the environment-the“problem”in perspective.Chemosphere115,95-99.
Trawiński,J.,Skibiński,R.,2017.Photolytic and photocatalytic degradation of tandospirone:determination of kinetics,identification of transformation products and in silico estimation of toxicity.Sci.Total Environ.591,775-798.
US EPA(United States Environmental Protection Agency),2016.User's Guide for T.E.S.T.(Toxicity Estimation Software Tool):AProgram to Estimate Toxicity from Molecular Structure.version 4.2.Available at.www.epa.gov/sites/production/files/2016-05/documents/600r16058.pdf,Accessed date:20 October2018.
US EPA(United States Environmental Protection Agency),2017a.The third unregulated contaminant monitoring rule(UCMR3):Data summary,January 2017.EPA 815-S-17-001.Office of Water(MS-140).
US EPA(United States Environmental Protection Agency),2017b.Methodology document for the ECOlogical Structure-Activity Relationship Model(ECOSAR)Class Program(Ecological Structure Activity Relationships).version 2.0.Available at.www.epa.gov/tsca-screening-tools/ecological-structure-activity-relationships-program-ecosar-methodology-document,Accessed date:15 October 2018.
Vinu,R.,Madras,G.,2011.Photocatalytic degradation of water pollutants using nano-TiO2.Energy efficiency and renewable energy through nanotechnology.In:Zang,L.(Ed.),Green Energy and Technology.Springer,London,pp.626-677.
Wang,W.L.,Wu,Q.Y.,Huang,N.,Wang,T.,Hu,H.Y.,2016.Synergistic effect between UV and chlorine(UV/chlorine)on the degradation of carbamazepine:influence factors and radical species.Water Res.98,190-198.
Wilde,M.L.,Menz,J.,Trautwein,C.,Leder,C.,Kümmerer,K.,2016.Environmental fate and effect assessment of thioridazine and its transformation products formed by photodegradation.Environ.Pollut.213,658-670.
Worth,A.P.,van Leeuwen,C.J.,Hartung,T.,2004.The prospects for using(Q)SARs in a changing political environment:high expectations and a key role for the Commission's Joint Research Centre.SAR QSAR Environ.Res.15(5-6),331-343.
Writer,J.H.,Ferrer,I.,Barber,L.B.,Thurman,E.M.,2013.Widespread occurrence of neuro-active pharmaceuticals and metabolites in 24 Minnesota rivers and wastewaters.Sci.Total Environ.461-462,519-527.
Yin,J.,Niu,Y.,Shao,B.,2017.Products of methotrexate during chlorination.J.Environ.Sci.55,100-108.
Yuzawa,H.,Aoki,M.,Otake,K.,Hattori,T.,Itoh,H.,Yoshida,H.,2012.Reaction mechanism of aromatic ring hydroxylation by water over platinum-loaded titanium oxide photocatalyst.J.Phys.Chem.C 116(48),25376-25387.
Zhou,S.,Xia,Y.,Li,T.,Yao,T.,Shi,Z.,Zhu,S.,et al.,2016.Degradation of carbamazepine by UV/chlorine advanced oxidation process and formation of disinfection by-products.Environ.Sci.Pollut.Res.23(16),16448-16455.