典型精神病药物在污水处理厂的存在与去除
|
摘要
本研究以3类22种典型精神病药物(7种镇静安眠类药物,9种抗精神分裂类药物和6种抗抑郁药物)为研究对象,采用液质联用(HPLC-MS/MS)技术构建了城市污水中痕量精神病药物检测方法,在此基础上调查了北京市普通生活污水和精神病医院生活污水(精神病药物集中排放源)中精神病药物浓度,以及普通城市污水处理厂和精神病医院生活污水处理站中不同处理工艺对精神病药物的去除效率与净化机制,为改进和优化污水处理工艺、制定环境质量标准提供基础数据和科学依据。
依据前期调研结果(文献及北京地区精神病医院中药物使用情况)确定如下常用精神病药物为研究对象：7种镇静安眠类药物(含抗焦虑、抗癫痫药物)、9种抗精神分裂症药物、6种抗抑郁症药物等。本研究中22种药物均具有胺基官能团(仲胺或叔胺),质谱检测时采用ESI+离子化方式,然后针对每种药物采用针泵进样方式优化确定其质谱检测的各项参数,并将质谱与液相色谱联用,优化液相色谱流动相及梯度洗脱条件,最终22种药物在12分钟内被完全分离,且被分析物工作曲线线性范围广(2-3个数量级),相关系数r均大于0.99。
本研究在样品富集过程中采用全自动固相萃取,选择合适的固相萃取填料(HLB Disk)及相应的洗脱溶剂(2%乙酸甲醇溶液),并对萃取过程中HLB萃取盘活化时间、上样溶液pH值、上样流速、萃取盘干燥时间及溶剂洗脱过程的控制等,建立了全自动固相萃取方法,除奥氮平、齐拉西酮、奋乃静、舒必利外,其他18种药物在纯水中加标回收率都在80%以上。实际污水样品成分复杂、基质干扰严重,污水样品的固相萃取溶液经过氨基柱净化后,除奥氮平、舒必利、齐拉西酮在生活污水原水中基质效应在60%以下外,其余19种药物基质效应被控制在60%-111%之间,方法中药物在进水和出水中的定量限为0.1～8ng L-1,并通过在生活污水进水和出水中低、中、高三个浓度的加标回收率进行校正,其方法最终得到确认,完全满足药物检测需要。
本研究针对北京市最大的三个污水处理厂以及北京市南北两个精神病医院中的污水中精神病药物进行调研。除氯硝西泮外,其他21种药物均在污水中被检出：在城市综合污水处理厂中氯氮平、舒必利、卡马西平和喹硫平浓度水平在10-100ng L-1之间,奥沙西泮、氯丙嗪苯海索、利培酮、氯米帕明、西酞普兰、氟西汀、舍曲林的浓度在检测限至10ng L-1之间,阿普唑仑、劳拉西泮、扎来普隆、奥氮平、齐拉西酮、阿立哌唑、奋乃静、帕罗西汀、氟伏沙明均未被检测到；而在精神病医院污水中氯氮平、舒必利和喹硫平浓度水平在2000～10000ng L-1之间,其余药物的浓度水平多数在检测限至500ng L-1之间。由此看出,精神病医院废水中精神病药物的浓度水平明显高于普通污水处理厂污水中药物浓度水平,精神病医院废水是城市污水中精神病药物的主要来源。
调研表明：药物在不同的污水处理厂中的去除情况差别较大。苯海索、奥氮平、氯氮平、利培酮、喹硫平等药物在不同污水处理工艺部分被去除,去除率在30%以上；其余药物在污水处理工艺中去除率很低,甚至去除率呈现负值。污水处理工艺不同工艺段中药物去除率变化可以发现：在一级处理过程中多数药物部分被去除,在二级处理过程中(生物处理),精神病药物的去除情况较好,12种药物的去除率在50%以上,但是经过三级处理(氯化作用),14种药物的去除率呈现负值,说明在生物处理过程中被去除的精神病药物主体结构未被破坏,三级处理后以原药的形式排放进入水环境。
In this study, we investigated3kinds of22typical psychiatric pharmaceuticals, including7anxiolytic-sedative-hypnotics,6antidepressants and9anti-schizophrenia drugs, and developed the method for the determination of them in municipal wastewater. On the basis, we continued to investigate the psychiatric pharmaceuticals concentrations levels in two psychiatric hospitals'(P-WWTPs) and three municipal (M-WWTPs) wastewater treatment plants in Bejing and then study their removal efficiency in five WWTPs with different treatment processes and purification mechanism. This study would contribute to improve and optimize the wastewater treatment process, provide the basic data and scientific basis to develop environmental quality standards.
Based on the preliminary investigations (the literatures and the drug usage of the psychiatric hospital in Beijing region), the following commonly psychiatric drugs were studied:7sedative hypnotic drugs (including anti-anxiety-epileptic drugs),9antipsychotic drugs,6antidepressant drugs. In this study, since all analytes present basic characteristics with their amine moieties, the positive ESI ionization mode was selected, and then the parameters of mass spectrometry were defined for each drug by the injection in needle pump. Then we combined mass spectrometry with the liquid chromatography and optimizedthe liquid chromatography mobile phase and gradient elution conditions. Finally, the22drugs were completely separated within12minutes, and the linear range of analytes was wide (over2orders of magnitude) with the r over0.99.
In this study, we utilized the automated solid phase extraction, and selected the suitable solid-phase extraction packing (HLB Disk) and the eluting solution (2%acetic acid methanol solution), after optimizing condition and dry time of the disk, the sample pH, the loading flow rate in the elution process, and established a fully automated solid-phase extraction method. In the method,19out of22pharmaceuticals in spiking experiments recoveries were more than80%, except olanzapine, ziprasidone, and perphenazine. Given that the municipal wastewater was complex resulting the matrix interference being serious, the SPE eluting solution should be pured using the amino column. After that the matrix effects of19pharmaceutical sranged from60%to111%, except olanzapine, ziprasidone, and perphenazine. The method quantitation limits were between0.1～8.0ng L-1in the WWTP's influent and effluent. After the spiked experiment at the low, middle, and high concentration, the method was confirmed ultimately.
In this study, the two P-WWTPs and three M-WWTPs were investigated in Beijing. Except clonazepam, other21kinds of pharmaceuticals in the wastewater were detected. In municipal wastewater, the concentrations of clozapine, sulpiride, carbamazepine and quetiapine were between10～100ng L-1, the concentrations of oxazepam, chlorpromazine, trihexyphenidyl, risperidone, clomipramine, citalopram, fluoxetine and sertraline ranged from MQL to10ng L-1, the rest pharmaceuticals of alprazolam, lorazepam, zaleplon, olanzapine, ziprasidone, aripiprazole, perphenazine, paroxetine and fluvoxamine were not detected. However, in psychiatric hospital wastewater, the concentrations of clozapine, sulpirideand quetiapine ranged between2000-10000ng L-1, the concentrations of the rest pharmaceuticals ranged from MQL to500ng L-1. This shows that the concentrations of psychiatric pharmaceuticals in the psychiatric hospital wastewater were significantly higher than that in municipal wastewater, and the psychiatric hospital wastewater is the main source of psychiatric pharmaceuticals in municipal wasterwter.
The research shows that the removals of the pharmaceuticals in WWTPs vary widely. trihexyphenidyl, olanzapine, clozapine, risperidone and quetiapine were partially removed in different WWTPs processes, with more than30%removal efficiency;the removal efficiencies of the other pharmaceuticals were very low, even being negative value. The varies of the removal of the psychiatric pharmaceuticals in the different WWTPs processes show that the most pharmaceuticals were partially removed in primary treatment; the pharmaceuticals were well removed in the secondary treatment (biological treatment), and the removals of12pharmaceuticals were more than50%; but after tertiary treatment (chlorination), the removal efficiencies of14pharmaceuticals were negative, which shows that the main structure of pharmaceuticals was not been destroyed in the biological treatment process and the pharmaceuticals were discharged into the water environment after the tertiary treatment. So More attentions should be paid to control the discharge of psychiatric pharmaceuticals from pyschiatric hospital.
依据前期调研结果(文献及北京地区精神病医院中药物使用情况)确定如下常用精神病药物为研究对象：7种镇静安眠类药物(含抗焦虑、抗癫痫药物)、9种抗精神分裂症药物、6种抗抑郁症药物等。本研究中22种药物均具有胺基官能团(仲胺或叔胺),质谱检测时采用ESI+离子化方式,然后针对每种药物采用针泵进样方式优化确定其质谱检测的各项参数,并将质谱与液相色谱联用,优化液相色谱流动相及梯度洗脱条件,最终22种药物在12分钟内被完全分离,且被分析物工作曲线线性范围广(2-3个数量级),相关系数r均大于0.99。
本研究在样品富集过程中采用全自动固相萃取,选择合适的固相萃取填料(HLB Disk)及相应的洗脱溶剂(2%乙酸甲醇溶液),并对萃取过程中HLB萃取盘活化时间、上样溶液pH值、上样流速、萃取盘干燥时间及溶剂洗脱过程的控制等,建立了全自动固相萃取方法,除奥氮平、齐拉西酮、奋乃静、舒必利外,其他18种药物在纯水中加标回收率都在80%以上。实际污水样品成分复杂、基质干扰严重,污水样品的固相萃取溶液经过氨基柱净化后,除奥氮平、舒必利、齐拉西酮在生活污水原水中基质效应在60%以下外,其余19种药物基质效应被控制在60%-111%之间,方法中药物在进水和出水中的定量限为0.1～8ng L-1,并通过在生活污水进水和出水中低、中、高三个浓度的加标回收率进行校正,其方法最终得到确认,完全满足药物检测需要。
本研究针对北京市最大的三个污水处理厂以及北京市南北两个精神病医院中的污水中精神病药物进行调研。除氯硝西泮外,其他21种药物均在污水中被检出：在城市综合污水处理厂中氯氮平、舒必利、卡马西平和喹硫平浓度水平在10-100ng L-1之间,奥沙西泮、氯丙嗪苯海索、利培酮、氯米帕明、西酞普兰、氟西汀、舍曲林的浓度在检测限至10ng L-1之间,阿普唑仑、劳拉西泮、扎来普隆、奥氮平、齐拉西酮、阿立哌唑、奋乃静、帕罗西汀、氟伏沙明均未被检测到；而在精神病医院污水中氯氮平、舒必利和喹硫平浓度水平在2000～10000ng L-1之间,其余药物的浓度水平多数在检测限至500ng L-1之间。由此看出,精神病医院废水中精神病药物的浓度水平明显高于普通污水处理厂污水中药物浓度水平,精神病医院废水是城市污水中精神病药物的主要来源。
调研表明：药物在不同的污水处理厂中的去除情况差别较大。苯海索、奥氮平、氯氮平、利培酮、喹硫平等药物在不同污水处理工艺部分被去除,去除率在30%以上；其余药物在污水处理工艺中去除率很低,甚至去除率呈现负值。污水处理工艺不同工艺段中药物去除率变化可以发现：在一级处理过程中多数药物部分被去除,在二级处理过程中(生物处理),精神病药物的去除情况较好,12种药物的去除率在50%以上,但是经过三级处理(氯化作用),14种药物的去除率呈现负值,说明在生物处理过程中被去除的精神病药物主体结构未被破坏,三级处理后以原药的形式排放进入水环境。
In this study, we investigated3kinds of22typical psychiatric pharmaceuticals, including7anxiolytic-sedative-hypnotics,6antidepressants and9anti-schizophrenia drugs, and developed the method for the determination of them in municipal wastewater. On the basis, we continued to investigate the psychiatric pharmaceuticals concentrations levels in two psychiatric hospitals'(P-WWTPs) and three municipal (M-WWTPs) wastewater treatment plants in Bejing and then study their removal efficiency in five WWTPs with different treatment processes and purification mechanism. This study would contribute to improve and optimize the wastewater treatment process, provide the basic data and scientific basis to develop environmental quality standards.
Based on the preliminary investigations (the literatures and the drug usage of the psychiatric hospital in Beijing region), the following commonly psychiatric drugs were studied:7sedative hypnotic drugs (including anti-anxiety-epileptic drugs),9antipsychotic drugs,6antidepressant drugs. In this study, since all analytes present basic characteristics with their amine moieties, the positive ESI ionization mode was selected, and then the parameters of mass spectrometry were defined for each drug by the injection in needle pump. Then we combined mass spectrometry with the liquid chromatography and optimizedthe liquid chromatography mobile phase and gradient elution conditions. Finally, the22drugs were completely separated within12minutes, and the linear range of analytes was wide (over2orders of magnitude) with the r over0.99.
In this study, we utilized the automated solid phase extraction, and selected the suitable solid-phase extraction packing (HLB Disk) and the eluting solution (2%acetic acid methanol solution), after optimizing condition and dry time of the disk, the sample pH, the loading flow rate in the elution process, and established a fully automated solid-phase extraction method. In the method,19out of22pharmaceuticals in spiking experiments recoveries were more than80%, except olanzapine, ziprasidone, and perphenazine. Given that the municipal wastewater was complex resulting the matrix interference being serious, the SPE eluting solution should be pured using the amino column. After that the matrix effects of19pharmaceutical sranged from60%to111%, except olanzapine, ziprasidone, and perphenazine. The method quantitation limits were between0.1～8.0ng L-1in the WWTP's influent and effluent. After the spiked experiment at the low, middle, and high concentration, the method was confirmed ultimately.
In this study, the two P-WWTPs and three M-WWTPs were investigated in Beijing. Except clonazepam, other21kinds of pharmaceuticals in the wastewater were detected. In municipal wastewater, the concentrations of clozapine, sulpiride, carbamazepine and quetiapine were between10～100ng L-1, the concentrations of oxazepam, chlorpromazine, trihexyphenidyl, risperidone, clomipramine, citalopram, fluoxetine and sertraline ranged from MQL to10ng L-1, the rest pharmaceuticals of alprazolam, lorazepam, zaleplon, olanzapine, ziprasidone, aripiprazole, perphenazine, paroxetine and fluvoxamine were not detected. However, in psychiatric hospital wastewater, the concentrations of clozapine, sulpirideand quetiapine ranged between2000-10000ng L-1, the concentrations of the rest pharmaceuticals ranged from MQL to500ng L-1. This shows that the concentrations of psychiatric pharmaceuticals in the psychiatric hospital wastewater were significantly higher than that in municipal wastewater, and the psychiatric hospital wastewater is the main source of psychiatric pharmaceuticals in municipal wasterwter.
The research shows that the removals of the pharmaceuticals in WWTPs vary widely. trihexyphenidyl, olanzapine, clozapine, risperidone and quetiapine were partially removed in different WWTPs processes, with more than30%removal efficiency;the removal efficiencies of the other pharmaceuticals were very low, even being negative value. The varies of the removal of the psychiatric pharmaceuticals in the different WWTPs processes show that the most pharmaceuticals were partially removed in primary treatment; the pharmaceuticals were well removed in the secondary treatment (biological treatment), and the removals of12pharmaceuticals were more than50%; but after tertiary treatment (chlorination), the removal efficiencies of14pharmaceuticals were negative, which shows that the main structure of pharmaceuticals was not been destroyed in the biological treatment process and the pharmaceuticals were discharged into the water environment after the tertiary treatment. So More attentions should be paid to control the discharge of psychiatric pharmaceuticals from pyschiatric hospital.
引文
[1]Boyd, G. R., Palmeri, J. M., et al., Pharmaceuticals and personal care products (PPCPs) and endocrine disrupting chemicals (EDCs) in stormwater canals and Bayou St. John in New Orleans, Louisiana, USA. Science of the Total Environment.2004,333 (1-3):137-148.
[2]Daughton, C. G, Ternes, T. A., Pharmaceuticals and personal care products in the environment: Agents of subtle change? Environmental Health Perspectives.1999,107:907-938.
[3]周雪飞,张亚雷等.城市污水中药物和个人护理用品的去除.同济大学学报(自然科学版).2008,(11)：1542-1546.
[4]Thomas, H., Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment:a review of recent research data. Toxicology Letters.2002,131(1-2):5-17.
[5]Bound, J. P., Voulvoulis, N., Pharmaceuticals in the aquatic environment—a comparison of risk assessment strategies. Chemosphere.2004,56 (11):1143-1155.
[6]Tauxe-Wuersch, A., De Alencastro, L. F., et al., Occurrence of several acidic drugs in sewage treatment plants in Switzerland and risk assessment. Water Research.2005,39 (9):1761-1772.
[7]贾瑷,胡建英等.环境中的医药品与个人护理品.化学进展.2009,(Z1)：389-399.
[8]Kobayashi, T., Suehiro, F., et al., Distribution and diversity of tetracycline resistance genes encoding ribosomal protection proteins in Mekong river sediments in Vietnam. FEMS Microbiology Ecology.2007,59 (3):729-737.
[9]Hu, J., Shi, J., et al., Phenotyping and Genotyping of Antibiotic-Resistant Escherichia coli Isolated from a Natural River Basin. Environmental Science & Technology.2008,42 (9):3415-3420.
[10]Garcia-Rodriguez, J. A, Garcia, A. C. G., In-vitro activities of quinolones against mycobacteria. Journal of Antimicrobial Chemotherapy.1993,32 (6):797-808.
[11]M(?)lbak, K., Baggesen, D. L., et al., An Outbreak of Multidrug-Resistant, Quinolone-Resistant Salmonella enterica Serotype Typhimurium DT104. New England Journal of Medicine.1999,341 (19):1420-1425.
[12]B, H.-S., Algal toxicity of antibacterial agents used in intensive farming. Chemosphere.2000, 40 (7):731-739.
[13]Fernandez, C., Alonso, C., et al., Ecotoxicological assessment of doxycycline in aged pig manure using multispecies soil systems. Science of the Total Environment.2004,323(1-3):63-69.
[14]Ciniglia, C., Cascone, C., et al., Application of methods for assessing the geno-and cytotoxicity of Triclosan to C. ehrenbergii. Journal of Hazardous Materials.2005,122 (3):227-232.
[15]Coogan, M. A., Edziyie, R. E., et al., Algal bioaccumulation of triclocarban, triclosan, and methyl-triclosan in a North Texas wastewater treatment plant receiving stream. Chemosphere.2007,67 (10):1911-1918.
[16]Sanderson, H., Brain, R. A., et al., Toxicity classification and evaluation of four pharmaceuticals classes:antibiotics, antineoplastics, cardiovascular, and sex hormones. Toxicology. 2004,203 (1-3):27-40.
[17]Hawkins, D. R., Elsom, L. F., et al., Dermal absorption and disposition of musk ambrette, musk ketone and musk xylene in human subjects. Toxicology Letters.2002,131 (3):147-151.
[18]Christian, M. S., Parker, R. M., et al., Developmental toxicity studies of four fragrances in rats. Toxicology Letters.1999,111 (1-2):169-174.
[19]Breitholtz, M., Wollenberger, L., et al, Effects of four synthetic musks on the life cycle of the harpacticoid copepod Nitocra spinipes. Aquatic Toxicology.2003,63 (2):103-118.
[20]Steinberg, P., Fischer, T., et al., Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline (AHTN). Toxicology Letters.1999,111 (1-2):151-160.
[21]Michael, C., Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid. Ecotoxicology and Environmental Safety.2004,59 (3):309-315.
[22]Flippin, J. L., Huggett, D., et al., Changes in the timing of reproduction following chronic exposure to ibuprofen in Japanese medaka, Oryzias latipes. Aquatic Toxicology.2007,81(1):73-78.
[23]Daught, C. G., http://epa.gov/nerlesdl/chemistry/pharma/.
[24]Lindberg, R. H., Wennberg, P., et al., Screening of Human Antibiotic Substances and Determination of Weekly Mass Flows in Five Sewage Treatment Plants in Sweden. Environmental Science & Technology.2005,39 (10):3421-3429.
[25]Miao, X.-S., Bishay, F., et al., Occurrence of Antimicrobials in the Final Effluents of Wastewater Treatment Plants in Canada. Environmental Science & Technology.2004,38 (13):3533-3541.
[26]Petrovic, M., Gros, M., et al., Multi-residue analysis of pharmaceuticals in wastewater by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Journal of Chromatography A.2006,1124(1-2):68-81.
[27]Occurrence of sulfonamide antibiotics in sewage treatment plants. Chinese Science Bulletin. 2008,(04):514-520.
[28]Vieno, N., Tuhkanen, T., et al., Elimination of pharmaceuticals in sewage treatment plants in Finland. Water Research.2007,41 (5):1001-1012.
[29]Kinney, C. A., Furlong, E. T., et al., Survey of Organic Wastewater Contaminants in Biosolids Destined for Land Application(?). Environmental Science & Technology.2006,40 (23):7207-7215.
[30]Kinney, C. A., Furlong, E. T., et al., Presence and distribution of wastewater-derived pharmaceuticals in soil irrigated with reclaimed water. Environmental Toxicology and Chemistry.2006, 25 (2):317-326.
[31]Hamscher, G., Sczesny, S., et al., Determination of Persistent Tetracycline Residues in Soil Fertilized with Liquid Manure by High-Performance Liquid Chromatography with Electrospray Ionization Tandem Mass Spectrometry. Analytical Chemistry.2002,74 (7):1509-1518.
[32]Kim, S.-C. and Carlson, K., Temporal and Spatial Trends in the Occurrence of Human and Veterinary Antibiotics in Aqueous and River Sediment Matrices. Environmental Science & Technology. 2006,41 (1):50-57.
[33]Kasprzyk-Hordern, B., Dinsdale, R. M., et al., The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK. Water Research.2008,42 (13):3498-3518.
[34]Kolpin, D. W., Furlong, E. T., et al., Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams,1999-2000:A National Reconnaissance. Environmental Science & Technology.2002,36 (6):1202-1211.
[35]Managaki, S., Murata, A., et al., Distribution of Macrolides, Sulfonamides, and Trimethoprim in Tropical Waters:Ubiquitous Occurrence of Veterinary Antibiotics in the Mekong Delta. Environmental Science & Technology.2007,41 (23):8004-8010.
[36]Peng, X., Yu, Y., et al., Occurrence of steroid estrogens, endocrine-disrupting phenols, and acid pharmaceutical residues in urban riverine water of the Pearl River Delta, South China. Science of the Total Environment.2008,397 (1-3):158-166.
[37]Barnes, K. K., Kolpin, D. W., et al., A national reconnaissance of pharmaceuticals and other organic wastewater contaminants in the United States - Ⅰ) Groundwater. Science of the Total Environment.2008,402 (2-3):192-200.
[38]Focazio, M. J., Kolpin, D. W., et al., A national reconnaissance for pharmaceuticals and other organic wastewater contaminants in the United States-Ⅱ) Untreated drinking water sources. Science of the Total Environment.2008,402 (2-3):201-216.
[39]Ye, Z., Weinberg, H. S., et al., Trace Analysis of Trimethoprim and Sulfonamide, Macrolide, Quinolone, and Tetracycline Antibiotics in Chlorinated Drinking Water Using Liquid Chromatography Electrospray Tandem Mass Spectrometry. Analytical Chemistry.2006,79 (3):1135-1144.
[40]Loraine, G. A. and Pettigrove, M. E., Seasonal Variations in Concentrations of Pharmaceuticals and Personal Care Products in Drinking Water and Reclaimed Wastewater in Southern California. Environmental Science & Technology.2005,40 (3):687-695.
[41]Rogers, H. R., Sources, behaviour and fate of organic contaminants during sewage treatment and in sewage sludges. Science of the Total Environment.1996,185(1-3):3-26.
[42]Velagaleti, R., Behavior of pharmaceutical drugs (human and animal health) in the environment. Drug information journal.1997,31:715-722.
[43]Ternes, T. A., Occurrence of drugs in German sewage treatment plants and rivers. Water Research.1998,32 (11):3245-3260.
[44]http://www.rxlist.com/script/main/hp.asp.
[45]周艳璞,白宗顺等.北京市安康医院门诊抗精神病药物的调查分析.首都医药.2007, (02)：43.
[46]付卫红,吉中孚等.住院精神病患者抗精神病药处方调查.药物流行病学杂志.2010,(03)：149-151.
[47]铁常乐,王传跃.我院2008年抑郁症住院患者精神药品应用分析.中国药房.2010,(26)：2406-2408.
[48]Calleja, M. C., Persoone, G., et al., COMPARATIVE ACUTE TOXICITY OF THE FIRST 50 MULTICENTER EVALUATION OF IN-VITRO CYTOTOXICITY CHEMICALS TO AQUATIC NON-VERTEBRATES. Archives of Environmental Contamination and Toxicology.1994,26 (1):69-78.
[49]Lilius, H., Hastbacka, T., et al., A COMPARISON OF THE TOXICITY OF 30 REFERENCE CHEMICALS TO DAPHNIA-MAGNA AND DAPHNIA-PULEX. Environmental Toxicology and Chemistry.1995,14 (12):2085-2088.
[50]Halling-Sorensen, B., Nielsen, S. N., et al., Occurrence, fate and effects of pharmaceutical substances in the environment-A review. Chemosphere.1998,36 (2):357-394.
[51]Nunes, B., Carvalho, F., et al., Acute toxicity of widely used pharmaceuticals in aquatic species:Gambusia holbrooki, Artemia parthenogenetica and Tetraselmis chuii. Ecotoxicology and Environmental Safety.2005,61 (3):413-419.
[52]Pascoe, D., Karntanut, W., et al., Do pharmaceuticals affect freshwater invertebrates? A study with the cnidarian Hydra vulgaris. Chemosphere.2003,51 (6):521-528.
[53]Brooks, B. W., Foran, C. M., et al., Aquatic ecotoxicology of fluoxetine. Toxicology Letters. 2003,142 (3):169-183.
[54]Brooks, B. W., Turner, P. K., et al., Waterbome and sediment toxicity of fluoxetine to select organisms. Chemosphere.2003,52 (1):135-142.
[55]Henry, T. B., Kwon, J. W., et al., Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia. Environmental Toxicology and Chemistry.2004,23 (9):2229-2233.
[56]Pery, A. R. R., Gust, M., et al., Fluoxetine effects assessment on the life cycle of aquatic invertebrates. Chemosphere.2008,73 (3):300-304.
[57]Stanley, J. K., Ramirez, A. J., et al., Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate. Chemosphere.2007,69 (1):9-16.
[58]Johnson, D. J., Sanderson, H., et al., Toxicity and hazard of selective serotonin reuptake inhibitor antidepressants fluoxetine, fluvoxamine, and sertraline to algae. Ecotoxicology and Environmental Safety.2007,67 (1):128-139.
[59]Richards, S. M. and Cole, S. E., A toxicity and hazard assessment of fourteen pharmaceuticals to Xenopus laevis larvae. Ecotoxicology.2006,15 (8):647-656.
[60]Caminada, D., Escher, C., et al., Cytotoxicity of pharmaceuticals found in aquatic systems: Comparison of PLHC-1 and RTG-2 fish cell lines. Aquatic Toxicology.2006,79 (2):114-123.
[61]Gust, M., Buronfosse, T., et al., Effects of fluoxetine on the reproduction of two prosobranch mollusks:Potamopyrgus antipodarum and Valvata piscinalis. Environmental Pollution.2009,157 (2):423-429.
[62]Crane, M., Watts, C., et al., Chronic aquatic environmental risks from exposure to human pharmaceuticals. Science of the Total Environment.2006,367 (1):23-41.
[63]Sanderson, H., Johnson, D. J., et al., Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish, daphnids and algae by ECOSAR screening. Toxicology Letters.2003,144 (3):383-395.
[64]Petrovic, M., Gros, M., et al., Multi-residue analysis of pharmaceuticals in wastewater by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Journal of Chromatography A.2006,1124 (1-2):68-81.
[65]Van Der Ven, K., Keil, D., et al., Effects of the antidepressant mianserin in zebrafish: Molecular markers of endocrine disruption. Chemosphere.2006,65 (10):1836-1845.
[66]Schultzt, M. M. and Furlong, E. T., Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS. Analytical Chemistry.2008,80 (5):1756-1762.
[67]Fong, P. and Molnar, N., Norfluoxetine Induces Spawning and Parturition in Estuarine and Freshwater Bivalves. Bulletin of Environmental Contamination and Toxicology.2008,81 (6):535-538.
[68]Ternes, T. A., Analytical methods for the determination of pharmaceuticals in aqueous environmental samples. Trac-Trends in Analytical Chemistry.2001,20 (8):419-434.
[69]Henry, T. B., Black, M. C., Acute and chronic toxicity of fluoxetine (selective serotonin reuptake inhibitor) in western mosquito fish. Archives of Environmental Contamination and Toxicology. 2008,54 (2):325-330.
[70]Fong, P. P., Zebra mussel spawning is induced in low concentrations of putative serotonin reuptake inhibitors. The Biological Bulletin.1998,194 (2) p143.
[71]Bound, J. P., Kitsou, K., et al., Household disposal of pharmaceuticals and perception of risk to the environment. Environmental Toxicology and Pharmacology.2006,21 (3):301-307.
[72]Ternes, T., Bonerz, M., et al., Determination of neutral pharmaceuticals in wastewater and rivers by liquid chromatography-electrospray tandem mass spectrometry. Journal of Chromatography A. 2001,938 (1-2):175-185.
[73]Snyder, S. A., Occurrence, treatment, and toxicological relevance of EDCs and pharmaceuticals in water. Ozone-Science & Engineering.2008,30 (1):65-69.
[74]Van Der Ven, K., Van Dongen, W., et al., Determination of diazepam in aquatic samples by capillary liquid chromatography-electrospray tandem mass spectrometry. Chemosphere.2004,57 (8):967-973.
[75]Wick, A., Fink, G., et al., Fate of beta blockers and psycho-active drugs in conventional wastewater treatment. Water Research.2009,43 (4):1060-1074.
[76]Baker, D. R., Kasprzyk-Hordern, B., Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography-positive electrospray ionisation tandem mass spectrometry. Journal of Chromatography A.2011,1218 (12):1620-1631.
[77]Kosma, C. I., Lambropoulou, D. A., et al., Occurrence and removal of PPCPs in municipal and hospital wastewaters in Greece. Journal of Hazardous Materials.2010,179 (1-3):804-817.
[78]Tarcomnicu, I., Van Nuijs, A. L. N., et al., Simultaneous determination of 15 top-prescribed pharmaceuticals and their metabolites in influent wastewater by reversed-phase liquid chromatography coupled to tandem mass spectrometry. Talanta.2011,83 (3):795-803.
[79]Vanderford, B. J., Snyder, S. A., Analysis of pharmaceuticals in water by isotope dilution liquid chromatography/tandem mass spectrometry. Environmental Science & Technology.2006,40 (23):7312-7320.
[80]Jelic, A., Gros, M., et al., Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during wastewater treatment. Water Research.2011,45 (3):1165-1176.
[81]Gracia-Lor, E., Sancho, J. V., et al., Multi-class determination of around 50 pharmaceuticals, including 26 antibiotics, in environmental and wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry. Journal of Chromatography A.2011,1218 (16):2264-2275.
[82]Sousa, M. A., Goncalves, C., et al., Cleanup strategies and advantages in the determination of several therapeutic classes of pharmaceuticals in wastewater samples by SPE-LC-MS/MS. Analytical and Bioanalytical Chemistry.2011,399 (2):807-822.
[83]Lajeunesse, A., Gagnon, C., et al., Determination of basic antidepressants and their n-desmethyl metabolites in raw sewage and wastewater using solid-phase extraction and liquid chromatography-Tandem mass spectrometry. Analytical Chemistry.2008,80 (14):5325-5333.
[84]Schultz, M. M., Furlong, E. T., et al., Antidepressant Pharmaceuticals in Two US Effluent-Impacted Streams:Occurrence and Fate in Water and Sediment, and Selective Uptake in Fish Neural Tissue. Environmental Science & Technology.2010,44 (6):1918-1925.
[85]Kosjek, T., Perko, S., et al., Environmental occurrence, fate and transformation of benzodiazepines in water treatment. Water Research.2012,46 (2):355-368.
[86]Stein, K., Ramil, M., et al., Analysis and sorption of psychoactive drugs onto sediment. Environmental Science & Technology.2008,42 (17):6415-6423.
[87]Calisto, V., Domingues, M. R. M., el al., Photodegradation of psychiatric pharmaceuticals in aquatic environments-Kinetics and photodegradation products. Water Research.2011,45 (18):6097-6106.
[88]Redshaw, C. H., Cooke, M. P., et al., Low biodegradability of fluoxetine HCl, diazepam and their human metabolites in sewage sludge-amended soil. Journal of Soils and Sediments.2008,8 (4):217-230.
[89]Clara, M., Strenn, B., et al., Removal of selected pharmaceuticals, fragrances and endocrine disrupting compounds in a membrane bioreactor and conventional wastewater treatment plants. Water Research.2005,39 (19):4797-4807.
[90]Miao, X. S., Yang, J. J., et al., Carbamazepine and its metabolites in wastewater and in biosolids in a municipal wastewater treatment plant. Environmental Science & Technology.2005,39 (19):7469-7475.
[91]Xue, W., Wu, C., et al., Elimination and fate of selected micro-organic pollutants in a full-scale anaerobic/anoxic/aerobic process combined with membrane bioreactor for municipal wastewater reclamation. Water Research.2010,44 (20):5999-6010.
[92]Debska, J., Kot-Wasik, A., et al., Fate and analysis of pharmaceutical residues in the aquatic environment. Critical Reviews in Analytical Chemistry.2004,34 (1):51-67.
[93]Kot-Wasik, A., Debska, J., et al., Analytical techniques in studies of the environmental fate of Pharmaceuticals and personal-care products. Trac-Trends in Analytical Chemistry.2007,26 (6):557-568.
[94]Calisto, V., Esteves, V. I., Psychiatric Pharmaceuticals in the environment. Chemosphere. 2009,77 (10):1257-1274.
[95]Ternes, T. A., Hirsch, R., et al., Methods for the determination of neutral drugs as well as betablockers and beta(2)-sympathomimetics in aqueous matrices using GC/MS and LC/MS/MS. Fresenius Journal of Analytical Chemistry.1998,362 (3):329-340.
[96]Sacher, F., Lang, F. T., et al., Pharmaceuticals in groundwaters-Analytical methods and results of a monitoring program in Baden-Wurttemberg, Germany. Journal of Chromatography A.2001, 938(1-2):199-210.
[97]Peschka, M., Eubeler, J. P., et al, Occurrence and fate of barbiturates in the aquatic environment. Environmental Science & Technology.2006,40 (23):7200-7206.
[98]Gros, M., Petrovic, M., et al., Development of a multi-residue analytical methodology based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for screening and trace level determination of Pharmaceuticals in surface and wastewaters. Talanta.2006,70 (4):678-690.
[99]Vasskog, T., Berger, U., et al., Selective serotonin reuptake inhibitors in sewage influents and effluents from Troms(?), Norway. Journal of Chromatography A.2006,1115 (1-2):187-195.
[100]Gracia-Lor, E., Sancho, J. V., et al, Simultaneous determination of acidic, neutral and basic Pharmaceuticals in urban wastewater by ultra high-pressure liquid chromatography-tandem mass spectrometry. Journal of Chromatography A.2010,1217 (5):622-632.
[101]Saracino, M. A., Gandolfi, O., et al, Determination of Olanzapine in rat brain using liquid chromatography with coulometric detection and a rapid solid-phase extraction procedure. Journal of Chromatography A.2006,1122 (1-2):21-27.
[102]Shinozuka, T., Terada, M., et al., Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method. Forensic Science International.2006,162 (1-3):108-112.
[103]Concheiro, M., De Castro, A., et al, Determination of illicit and medicinal drugs and their metabolites in oral fluid and preserved oral fluid by liquid chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry.2008,391 (6):2329-2338.
[104]Chu, S., Metcalfe, C. D., Analysis of paroxetine, fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction, mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry. Journal of Chromatography A.2007,1163 (1-2):112-118.
[105]Uddin, M. N., Samanidou, V. F., et al, Development and validation of an HPLC method for the determination of benzodiazepines and tricyclic antidepressants in biological fluids after sequential SPE. Journal of Separation Science.2008,31 (13):2358-2370.
[106]Hummel, D., Loffler, D., et al., Simultaneous determination of psychoactive drugs and their metabolites in aqueous matrices by liquid chromatography mass spectrometry. Environmental Science & Technology.2006,40 (23):7321-7328.
[107]Vasskog, T., Berger, U., et al, Selective serotonin reuptake inhibitors in sewage influents and effluents from Tromso, Norway. Journal of Chromatography A.2006,1115 (1-2):187-195.
[108]Chu, S., Metcalfe, C. D., Analysis of paroxetine, fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction, mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry. Journal of Chromatography A.2007,1163 (1-2):112-118.
[109]Shao, B., Chen, D., et al, Determination of 76 pharmaceutical drugs by liquid chromatography-tandem mass spectrometry in slaughterhouse wastewater. Journal of Chromatography A.2009,1216(47):8312-8318.
[110]Gros, M., Petrovic, M., et al., Multi-residue analytical methods using LC-tandem MS for the determination of pharmaceuticals in environmental and wastewater samples:a review. Analytical and Bioanalytical Chemistry.2006,386 (4):941-952.
[111]Nirogi, R. V. S., Kandikere, V. N., et al., Development and validation of a sensitive liquid chromatography/electrospray tandem mass spectrometry assay for the quantification of olanzapine in human plasma. Journal of Pharmaceutical and Biomedical Analysis.2006,41 (3):935-942.
[112]Kasper, S. C., Mattiuz, E. L., et al., Determination of olanzapine in human breast milk by high-performance liquid chromatography with electrochemical detection. Journal of Chromatography B: Biomedical Sciences and Applications.1999,726 (1-2):203-209.
[113]Shao, B., Chen, D., et al., Determination of 76 pharmaceutical drugs by liquid chromatography-tandem mass spectrometry in slaughterhouse wastewater. Journal of Chromatography A.2009,1216 (47):8312-8318.
[114]Matuszewski, B. K., Constanzer, M. L., et al., Strategies for the Assessment of Matrix Effect in Quantitative Bioanalytical Methods Based on HPLC-MS/MS. Analytical Chemistry.2003,75 (13):3019-3030.
[115]Kruve, A., Kunnapas, A., et al., Matrix effects in pesticide multi-residue analysis by liquid chromatography-mass spectrometry. Journal of Chromatography A.2008,1187 (1-2):58-66.
[116]Ingrand, V., Herry, G., et al., Analysis of steroid hormones in effluents of wastewater treatment plants by liquid chromatography-tandem mass spectrometry. Journal of Chromatography A. 2003,1020 (1):99-104.
[117]Parera, J., Santos, F. J., et al., Microwave-assisted extraction versus Soxhlet extraction for the analysis of short-chain chlorinated alkanes in sediments. Journal of Chromatography A.2004,1046 (1-2):19-26.
[118]Westbom, R., Thorneby, L., et al., Development of a solid-phase extraction method for the determination of poly chlorinated biphenyls in water. Journal of Chromatography A.2004,1033 (1):1-8.
[119]Esteve-Turrillas, F. A., Aman, C. S., et al., Microwave-assisted extraction of pyrethroid insecticides from soil. Analytica Chimica Acta.2004,522 (1):73-78.
[120]Fatta-Kassinos, D., Hapeshi, E., et al., Existence of Pharmaceutical Compounds in Tertiary Treated Urban Wastewater that is Utilized for Reuse Applications. Water Resources Management.2011, 25(4):1183-1193.
[121]Hu, J. Y., Chang, H., et al., Detection, Occurrence and Fate of Indirubin in Municipal Sewage Treatment Plants. Environmental Science & Technology.2008,42 (22):8339-8344.
[122]Sui, Q., Huang, J., et al., Occurrence and removal of pharmaceuticals, caffeine and DEET in wastewater treatment plants of Beijing, China. Water Research.2010,44 (2):417-426.
[123]Miao, X. S. and Metcalfe, C. D., Determination of carbamazepine and its metabolites in aqueous samples using liquid chromatography-electrospray tandem mass spectrometry. Analytical Chemistry.2003,75 (15):3731-3738.
[124]Petrovic, M., Hernando, M. D., et al., Liquid chromatography-tandem mass spectrometry for the analysis of pharmaceutical residues in environmental samples:a review. Journal of Chromatography A.2005,1067 (1-2):1-14.
[125]Thomas, P. M. and Foster, G. D., Tracking acidic pharmaceuticals, caffeine, and triclosan through the wastewater treatment process. Environmental Toxicology and Chemistry.2005,24 (1):25-30.
[126]Cirja, M., Ivashechkin, P., et al., Factors affecting the removal of organic micropollutants from wastewater in conventional treatment plants (CTP) and membrane bioreactors (MBR). Reviews in Environmental Science and Biotechnology.2008,7 (1):61-78.
[127]Jones, O. H., Voulvoulis, N., et al., The occurrence and removal of selected pharmaceutical compounds in a sewage treatment works utilising activated sludge treatment. Environmental Pollution. 2007,145 (3):738-744.
[128]Nakada, N., Shinohara, H., et al., Removal of selected pharmaceuticals and personal care products (PPCPs) and endocrine-disrupting chemicals (EDCs) during sand filtration and ozonation at a municipal sewage treatment plant. Water Research.2007,41 (19):4373-4382.
[129]Mcdowell, D. C., Huber, M. M., et al., Ozonation of Carbamazepine in Drinking Water: Identification and Kinetic Study of Major Oxidation Products. Environmental Science & Technology. 2005,39 (20):8014-8022.
[2]Daughton, C. G, Ternes, T. A., Pharmaceuticals and personal care products in the environment: Agents of subtle change? Environmental Health Perspectives.1999,107:907-938.
[3]周雪飞,张亚雷等.城市污水中药物和个人护理用品的去除.同济大学学报(自然科学版).2008,(11)：1542-1546.
[4]Thomas, H., Occurrence, fate, and removal of pharmaceutical residues in the aquatic environment:a review of recent research data. Toxicology Letters.2002,131(1-2):5-17.
[5]Bound, J. P., Voulvoulis, N., Pharmaceuticals in the aquatic environment—a comparison of risk assessment strategies. Chemosphere.2004,56 (11):1143-1155.
[6]Tauxe-Wuersch, A., De Alencastro, L. F., et al., Occurrence of several acidic drugs in sewage treatment plants in Switzerland and risk assessment. Water Research.2005,39 (9):1761-1772.
[7]贾瑷,胡建英等.环境中的医药品与个人护理品.化学进展.2009,(Z1)：389-399.
[8]Kobayashi, T., Suehiro, F., et al., Distribution and diversity of tetracycline resistance genes encoding ribosomal protection proteins in Mekong river sediments in Vietnam. FEMS Microbiology Ecology.2007,59 (3):729-737.
[9]Hu, J., Shi, J., et al., Phenotyping and Genotyping of Antibiotic-Resistant Escherichia coli Isolated from a Natural River Basin. Environmental Science & Technology.2008,42 (9):3415-3420.
[10]Garcia-Rodriguez, J. A, Garcia, A. C. G., In-vitro activities of quinolones against mycobacteria. Journal of Antimicrobial Chemotherapy.1993,32 (6):797-808.
[11]M(?)lbak, K., Baggesen, D. L., et al., An Outbreak of Multidrug-Resistant, Quinolone-Resistant Salmonella enterica Serotype Typhimurium DT104. New England Journal of Medicine.1999,341 (19):1420-1425.
[12]B, H.-S., Algal toxicity of antibacterial agents used in intensive farming. Chemosphere.2000, 40 (7):731-739.
[13]Fernandez, C., Alonso, C., et al., Ecotoxicological assessment of doxycycline in aged pig manure using multispecies soil systems. Science of the Total Environment.2004,323(1-3):63-69.
[14]Ciniglia, C., Cascone, C., et al., Application of methods for assessing the geno-and cytotoxicity of Triclosan to C. ehrenbergii. Journal of Hazardous Materials.2005,122 (3):227-232.
[15]Coogan, M. A., Edziyie, R. E., et al., Algal bioaccumulation of triclocarban, triclosan, and methyl-triclosan in a North Texas wastewater treatment plant receiving stream. Chemosphere.2007,67 (10):1911-1918.
[16]Sanderson, H., Brain, R. A., et al., Toxicity classification and evaluation of four pharmaceuticals classes:antibiotics, antineoplastics, cardiovascular, and sex hormones. Toxicology. 2004,203 (1-3):27-40.
[17]Hawkins, D. R., Elsom, L. F., et al., Dermal absorption and disposition of musk ambrette, musk ketone and musk xylene in human subjects. Toxicology Letters.2002,131 (3):147-151.
[18]Christian, M. S., Parker, R. M., et al., Developmental toxicity studies of four fragrances in rats. Toxicology Letters.1999,111 (1-2):169-174.
[19]Breitholtz, M., Wollenberger, L., et al, Effects of four synthetic musks on the life cycle of the harpacticoid copepod Nitocra spinipes. Aquatic Toxicology.2003,63 (2):103-118.
[20]Steinberg, P., Fischer, T., et al., Acute hepatotoxicity of the polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline (AHTN). Toxicology Letters.1999,111 (1-2):151-160.
[21]Michael, C., Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid. Ecotoxicology and Environmental Safety.2004,59 (3):309-315.
[22]Flippin, J. L., Huggett, D., et al., Changes in the timing of reproduction following chronic exposure to ibuprofen in Japanese medaka, Oryzias latipes. Aquatic Toxicology.2007,81(1):73-78.
[23]Daught, C. G., http://epa.gov/nerlesdl/chemistry/pharma/.
[24]Lindberg, R. H., Wennberg, P., et al., Screening of Human Antibiotic Substances and Determination of Weekly Mass Flows in Five Sewage Treatment Plants in Sweden. Environmental Science & Technology.2005,39 (10):3421-3429.
[25]Miao, X.-S., Bishay, F., et al., Occurrence of Antimicrobials in the Final Effluents of Wastewater Treatment Plants in Canada. Environmental Science & Technology.2004,38 (13):3533-3541.
[26]Petrovic, M., Gros, M., et al., Multi-residue analysis of pharmaceuticals in wastewater by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Journal of Chromatography A.2006,1124(1-2):68-81.
[27]Occurrence of sulfonamide antibiotics in sewage treatment plants. Chinese Science Bulletin. 2008,(04):514-520.
[28]Vieno, N., Tuhkanen, T., et al., Elimination of pharmaceuticals in sewage treatment plants in Finland. Water Research.2007,41 (5):1001-1012.
[29]Kinney, C. A., Furlong, E. T., et al., Survey of Organic Wastewater Contaminants in Biosolids Destined for Land Application(?). Environmental Science & Technology.2006,40 (23):7207-7215.
[30]Kinney, C. A., Furlong, E. T., et al., Presence and distribution of wastewater-derived pharmaceuticals in soil irrigated with reclaimed water. Environmental Toxicology and Chemistry.2006, 25 (2):317-326.
[31]Hamscher, G., Sczesny, S., et al., Determination of Persistent Tetracycline Residues in Soil Fertilized with Liquid Manure by High-Performance Liquid Chromatography with Electrospray Ionization Tandem Mass Spectrometry. Analytical Chemistry.2002,74 (7):1509-1518.
[32]Kim, S.-C. and Carlson, K., Temporal and Spatial Trends in the Occurrence of Human and Veterinary Antibiotics in Aqueous and River Sediment Matrices. Environmental Science & Technology. 2006,41 (1):50-57.
[33]Kasprzyk-Hordern, B., Dinsdale, R. M., et al., The occurrence of pharmaceuticals, personal care products, endocrine disruptors and illicit drugs in surface water in South Wales, UK. Water Research.2008,42 (13):3498-3518.
[34]Kolpin, D. W., Furlong, E. T., et al., Pharmaceuticals, Hormones, and Other Organic Wastewater Contaminants in U.S. Streams,1999-2000:A National Reconnaissance. Environmental Science & Technology.2002,36 (6):1202-1211.
[35]Managaki, S., Murata, A., et al., Distribution of Macrolides, Sulfonamides, and Trimethoprim in Tropical Waters:Ubiquitous Occurrence of Veterinary Antibiotics in the Mekong Delta. Environmental Science & Technology.2007,41 (23):8004-8010.
[36]Peng, X., Yu, Y., et al., Occurrence of steroid estrogens, endocrine-disrupting phenols, and acid pharmaceutical residues in urban riverine water of the Pearl River Delta, South China. Science of the Total Environment.2008,397 (1-3):158-166.
[37]Barnes, K. K., Kolpin, D. W., et al., A national reconnaissance of pharmaceuticals and other organic wastewater contaminants in the United States - Ⅰ) Groundwater. Science of the Total Environment.2008,402 (2-3):192-200.
[38]Focazio, M. J., Kolpin, D. W., et al., A national reconnaissance for pharmaceuticals and other organic wastewater contaminants in the United States-Ⅱ) Untreated drinking water sources. Science of the Total Environment.2008,402 (2-3):201-216.
[39]Ye, Z., Weinberg, H. S., et al., Trace Analysis of Trimethoprim and Sulfonamide, Macrolide, Quinolone, and Tetracycline Antibiotics in Chlorinated Drinking Water Using Liquid Chromatography Electrospray Tandem Mass Spectrometry. Analytical Chemistry.2006,79 (3):1135-1144.
[40]Loraine, G. A. and Pettigrove, M. E., Seasonal Variations in Concentrations of Pharmaceuticals and Personal Care Products in Drinking Water and Reclaimed Wastewater in Southern California. Environmental Science & Technology.2005,40 (3):687-695.
[41]Rogers, H. R., Sources, behaviour and fate of organic contaminants during sewage treatment and in sewage sludges. Science of the Total Environment.1996,185(1-3):3-26.
[42]Velagaleti, R., Behavior of pharmaceutical drugs (human and animal health) in the environment. Drug information journal.1997,31:715-722.
[43]Ternes, T. A., Occurrence of drugs in German sewage treatment plants and rivers. Water Research.1998,32 (11):3245-3260.
[44]http://www.rxlist.com/script/main/hp.asp.
[45]周艳璞,白宗顺等.北京市安康医院门诊抗精神病药物的调查分析.首都医药.2007, (02)：43.
[46]付卫红,吉中孚等.住院精神病患者抗精神病药处方调查.药物流行病学杂志.2010,(03)：149-151.
[47]铁常乐,王传跃.我院2008年抑郁症住院患者精神药品应用分析.中国药房.2010,(26)：2406-2408.
[48]Calleja, M. C., Persoone, G., et al., COMPARATIVE ACUTE TOXICITY OF THE FIRST 50 MULTICENTER EVALUATION OF IN-VITRO CYTOTOXICITY CHEMICALS TO AQUATIC NON-VERTEBRATES. Archives of Environmental Contamination and Toxicology.1994,26 (1):69-78.
[49]Lilius, H., Hastbacka, T., et al., A COMPARISON OF THE TOXICITY OF 30 REFERENCE CHEMICALS TO DAPHNIA-MAGNA AND DAPHNIA-PULEX. Environmental Toxicology and Chemistry.1995,14 (12):2085-2088.
[50]Halling-Sorensen, B., Nielsen, S. N., et al., Occurrence, fate and effects of pharmaceutical substances in the environment-A review. Chemosphere.1998,36 (2):357-394.
[51]Nunes, B., Carvalho, F., et al., Acute toxicity of widely used pharmaceuticals in aquatic species:Gambusia holbrooki, Artemia parthenogenetica and Tetraselmis chuii. Ecotoxicology and Environmental Safety.2005,61 (3):413-419.
[52]Pascoe, D., Karntanut, W., et al., Do pharmaceuticals affect freshwater invertebrates? A study with the cnidarian Hydra vulgaris. Chemosphere.2003,51 (6):521-528.
[53]Brooks, B. W., Foran, C. M., et al., Aquatic ecotoxicology of fluoxetine. Toxicology Letters. 2003,142 (3):169-183.
[54]Brooks, B. W., Turner, P. K., et al., Waterbome and sediment toxicity of fluoxetine to select organisms. Chemosphere.2003,52 (1):135-142.
[55]Henry, T. B., Kwon, J. W., et al., Acute and chronic toxicity of five selective serotonin reuptake inhibitors in Ceriodaphnia dubia. Environmental Toxicology and Chemistry.2004,23 (9):2229-2233.
[56]Pery, A. R. R., Gust, M., et al., Fluoxetine effects assessment on the life cycle of aquatic invertebrates. Chemosphere.2008,73 (3):300-304.
[57]Stanley, J. K., Ramirez, A. J., et al., Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate. Chemosphere.2007,69 (1):9-16.
[58]Johnson, D. J., Sanderson, H., et al., Toxicity and hazard of selective serotonin reuptake inhibitor antidepressants fluoxetine, fluvoxamine, and sertraline to algae. Ecotoxicology and Environmental Safety.2007,67 (1):128-139.
[59]Richards, S. M. and Cole, S. E., A toxicity and hazard assessment of fourteen pharmaceuticals to Xenopus laevis larvae. Ecotoxicology.2006,15 (8):647-656.
[60]Caminada, D., Escher, C., et al., Cytotoxicity of pharmaceuticals found in aquatic systems: Comparison of PLHC-1 and RTG-2 fish cell lines. Aquatic Toxicology.2006,79 (2):114-123.
[61]Gust, M., Buronfosse, T., et al., Effects of fluoxetine on the reproduction of two prosobranch mollusks:Potamopyrgus antipodarum and Valvata piscinalis. Environmental Pollution.2009,157 (2):423-429.
[62]Crane, M., Watts, C., et al., Chronic aquatic environmental risks from exposure to human pharmaceuticals. Science of the Total Environment.2006,367 (1):23-41.
[63]Sanderson, H., Johnson, D. J., et al., Probabilistic hazard assessment of environmentally occurring pharmaceuticals toxicity to fish, daphnids and algae by ECOSAR screening. Toxicology Letters.2003,144 (3):383-395.
[64]Petrovic, M., Gros, M., et al., Multi-residue analysis of pharmaceuticals in wastewater by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry. Journal of Chromatography A.2006,1124 (1-2):68-81.
[65]Van Der Ven, K., Keil, D., et al., Effects of the antidepressant mianserin in zebrafish: Molecular markers of endocrine disruption. Chemosphere.2006,65 (10):1836-1845.
[66]Schultzt, M. M. and Furlong, E. T., Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS. Analytical Chemistry.2008,80 (5):1756-1762.
[67]Fong, P. and Molnar, N., Norfluoxetine Induces Spawning and Parturition in Estuarine and Freshwater Bivalves. Bulletin of Environmental Contamination and Toxicology.2008,81 (6):535-538.
[68]Ternes, T. A., Analytical methods for the determination of pharmaceuticals in aqueous environmental samples. Trac-Trends in Analytical Chemistry.2001,20 (8):419-434.
[69]Henry, T. B., Black, M. C., Acute and chronic toxicity of fluoxetine (selective serotonin reuptake inhibitor) in western mosquito fish. Archives of Environmental Contamination and Toxicology. 2008,54 (2):325-330.
[70]Fong, P. P., Zebra mussel spawning is induced in low concentrations of putative serotonin reuptake inhibitors. The Biological Bulletin.1998,194 (2) p143.
[71]Bound, J. P., Kitsou, K., et al., Household disposal of pharmaceuticals and perception of risk to the environment. Environmental Toxicology and Pharmacology.2006,21 (3):301-307.
[72]Ternes, T., Bonerz, M., et al., Determination of neutral pharmaceuticals in wastewater and rivers by liquid chromatography-electrospray tandem mass spectrometry. Journal of Chromatography A. 2001,938 (1-2):175-185.
[73]Snyder, S. A., Occurrence, treatment, and toxicological relevance of EDCs and pharmaceuticals in water. Ozone-Science & Engineering.2008,30 (1):65-69.
[74]Van Der Ven, K., Van Dongen, W., et al., Determination of diazepam in aquatic samples by capillary liquid chromatography-electrospray tandem mass spectrometry. Chemosphere.2004,57 (8):967-973.
[75]Wick, A., Fink, G., et al., Fate of beta blockers and psycho-active drugs in conventional wastewater treatment. Water Research.2009,43 (4):1060-1074.
[76]Baker, D. R., Kasprzyk-Hordern, B., Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography-positive electrospray ionisation tandem mass spectrometry. Journal of Chromatography A.2011,1218 (12):1620-1631.
[77]Kosma, C. I., Lambropoulou, D. A., et al., Occurrence and removal of PPCPs in municipal and hospital wastewaters in Greece. Journal of Hazardous Materials.2010,179 (1-3):804-817.
[78]Tarcomnicu, I., Van Nuijs, A. L. N., et al., Simultaneous determination of 15 top-prescribed pharmaceuticals and their metabolites in influent wastewater by reversed-phase liquid chromatography coupled to tandem mass spectrometry. Talanta.2011,83 (3):795-803.
[79]Vanderford, B. J., Snyder, S. A., Analysis of pharmaceuticals in water by isotope dilution liquid chromatography/tandem mass spectrometry. Environmental Science & Technology.2006,40 (23):7312-7320.
[80]Jelic, A., Gros, M., et al., Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during wastewater treatment. Water Research.2011,45 (3):1165-1176.
[81]Gracia-Lor, E., Sancho, J. V., et al., Multi-class determination of around 50 pharmaceuticals, including 26 antibiotics, in environmental and wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry. Journal of Chromatography A.2011,1218 (16):2264-2275.
[82]Sousa, M. A., Goncalves, C., et al., Cleanup strategies and advantages in the determination of several therapeutic classes of pharmaceuticals in wastewater samples by SPE-LC-MS/MS. Analytical and Bioanalytical Chemistry.2011,399 (2):807-822.
[83]Lajeunesse, A., Gagnon, C., et al., Determination of basic antidepressants and their n-desmethyl metabolites in raw sewage and wastewater using solid-phase extraction and liquid chromatography-Tandem mass spectrometry. Analytical Chemistry.2008,80 (14):5325-5333.
[84]Schultz, M. M., Furlong, E. T., et al., Antidepressant Pharmaceuticals in Two US Effluent-Impacted Streams:Occurrence and Fate in Water and Sediment, and Selective Uptake in Fish Neural Tissue. Environmental Science & Technology.2010,44 (6):1918-1925.
[85]Kosjek, T., Perko, S., et al., Environmental occurrence, fate and transformation of benzodiazepines in water treatment. Water Research.2012,46 (2):355-368.
[86]Stein, K., Ramil, M., et al., Analysis and sorption of psychoactive drugs onto sediment. Environmental Science & Technology.2008,42 (17):6415-6423.
[87]Calisto, V., Domingues, M. R. M., el al., Photodegradation of psychiatric pharmaceuticals in aquatic environments-Kinetics and photodegradation products. Water Research.2011,45 (18):6097-6106.
[88]Redshaw, C. H., Cooke, M. P., et al., Low biodegradability of fluoxetine HCl, diazepam and their human metabolites in sewage sludge-amended soil. Journal of Soils and Sediments.2008,8 (4):217-230.
[89]Clara, M., Strenn, B., et al., Removal of selected pharmaceuticals, fragrances and endocrine disrupting compounds in a membrane bioreactor and conventional wastewater treatment plants. Water Research.2005,39 (19):4797-4807.
[90]Miao, X. S., Yang, J. J., et al., Carbamazepine and its metabolites in wastewater and in biosolids in a municipal wastewater treatment plant. Environmental Science & Technology.2005,39 (19):7469-7475.
[91]Xue, W., Wu, C., et al., Elimination and fate of selected micro-organic pollutants in a full-scale anaerobic/anoxic/aerobic process combined with membrane bioreactor for municipal wastewater reclamation. Water Research.2010,44 (20):5999-6010.
[92]Debska, J., Kot-Wasik, A., et al., Fate and analysis of pharmaceutical residues in the aquatic environment. Critical Reviews in Analytical Chemistry.2004,34 (1):51-67.
[93]Kot-Wasik, A., Debska, J., et al., Analytical techniques in studies of the environmental fate of Pharmaceuticals and personal-care products. Trac-Trends in Analytical Chemistry.2007,26 (6):557-568.
[94]Calisto, V., Esteves, V. I., Psychiatric Pharmaceuticals in the environment. Chemosphere. 2009,77 (10):1257-1274.
[95]Ternes, T. A., Hirsch, R., et al., Methods for the determination of neutral drugs as well as betablockers and beta(2)-sympathomimetics in aqueous matrices using GC/MS and LC/MS/MS. Fresenius Journal of Analytical Chemistry.1998,362 (3):329-340.
[96]Sacher, F., Lang, F. T., et al., Pharmaceuticals in groundwaters-Analytical methods and results of a monitoring program in Baden-Wurttemberg, Germany. Journal of Chromatography A.2001, 938(1-2):199-210.
[97]Peschka, M., Eubeler, J. P., et al, Occurrence and fate of barbiturates in the aquatic environment. Environmental Science & Technology.2006,40 (23):7200-7206.
[98]Gros, M., Petrovic, M., et al., Development of a multi-residue analytical methodology based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) for screening and trace level determination of Pharmaceuticals in surface and wastewaters. Talanta.2006,70 (4):678-690.
[99]Vasskog, T., Berger, U., et al., Selective serotonin reuptake inhibitors in sewage influents and effluents from Troms(?), Norway. Journal of Chromatography A.2006,1115 (1-2):187-195.
[100]Gracia-Lor, E., Sancho, J. V., et al, Simultaneous determination of acidic, neutral and basic Pharmaceuticals in urban wastewater by ultra high-pressure liquid chromatography-tandem mass spectrometry. Journal of Chromatography A.2010,1217 (5):622-632.
[101]Saracino, M. A., Gandolfi, O., et al, Determination of Olanzapine in rat brain using liquid chromatography with coulometric detection and a rapid solid-phase extraction procedure. Journal of Chromatography A.2006,1122 (1-2):21-27.
[102]Shinozuka, T., Terada, M., et al., Solid-phase extraction and analysis of 20 antidepressant drugs in human plasma by LC/MS with SSI method. Forensic Science International.2006,162 (1-3):108-112.
[103]Concheiro, M., De Castro, A., et al, Determination of illicit and medicinal drugs and their metabolites in oral fluid and preserved oral fluid by liquid chromatography-tandem mass spectrometry. Analytical and Bioanalytical Chemistry.2008,391 (6):2329-2338.
[104]Chu, S., Metcalfe, C. D., Analysis of paroxetine, fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction, mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry. Journal of Chromatography A.2007,1163 (1-2):112-118.
[105]Uddin, M. N., Samanidou, V. F., et al, Development and validation of an HPLC method for the determination of benzodiazepines and tricyclic antidepressants in biological fluids after sequential SPE. Journal of Separation Science.2008,31 (13):2358-2370.
[106]Hummel, D., Loffler, D., et al., Simultaneous determination of psychoactive drugs and their metabolites in aqueous matrices by liquid chromatography mass spectrometry. Environmental Science & Technology.2006,40 (23):7321-7328.
[107]Vasskog, T., Berger, U., et al, Selective serotonin reuptake inhibitors in sewage influents and effluents from Tromso, Norway. Journal of Chromatography A.2006,1115 (1-2):187-195.
[108]Chu, S., Metcalfe, C. D., Analysis of paroxetine, fluoxetine and norfluoxetine in fish tissues using pressurized liquid extraction, mixed mode solid phase extraction cleanup and liquid chromatography-tandem mass spectrometry. Journal of Chromatography A.2007,1163 (1-2):112-118.
[109]Shao, B., Chen, D., et al, Determination of 76 pharmaceutical drugs by liquid chromatography-tandem mass spectrometry in slaughterhouse wastewater. Journal of Chromatography A.2009,1216(47):8312-8318.
[110]Gros, M., Petrovic, M., et al., Multi-residue analytical methods using LC-tandem MS for the determination of pharmaceuticals in environmental and wastewater samples:a review. Analytical and Bioanalytical Chemistry.2006,386 (4):941-952.
[111]Nirogi, R. V. S., Kandikere, V. N., et al., Development and validation of a sensitive liquid chromatography/electrospray tandem mass spectrometry assay for the quantification of olanzapine in human plasma. Journal of Pharmaceutical and Biomedical Analysis.2006,41 (3):935-942.
[112]Kasper, S. C., Mattiuz, E. L., et al., Determination of olanzapine in human breast milk by high-performance liquid chromatography with electrochemical detection. Journal of Chromatography B: Biomedical Sciences and Applications.1999,726 (1-2):203-209.
[113]Shao, B., Chen, D., et al., Determination of 76 pharmaceutical drugs by liquid chromatography-tandem mass spectrometry in slaughterhouse wastewater. Journal of Chromatography A.2009,1216 (47):8312-8318.
[114]Matuszewski, B. K., Constanzer, M. L., et al., Strategies for the Assessment of Matrix Effect in Quantitative Bioanalytical Methods Based on HPLC-MS/MS. Analytical Chemistry.2003,75 (13):3019-3030.
[115]Kruve, A., Kunnapas, A., et al., Matrix effects in pesticide multi-residue analysis by liquid chromatography-mass spectrometry. Journal of Chromatography A.2008,1187 (1-2):58-66.
[116]Ingrand, V., Herry, G., et al., Analysis of steroid hormones in effluents of wastewater treatment plants by liquid chromatography-tandem mass spectrometry. Journal of Chromatography A. 2003,1020 (1):99-104.
[117]Parera, J., Santos, F. J., et al., Microwave-assisted extraction versus Soxhlet extraction for the analysis of short-chain chlorinated alkanes in sediments. Journal of Chromatography A.2004,1046 (1-2):19-26.
[118]Westbom, R., Thorneby, L., et al., Development of a solid-phase extraction method for the determination of poly chlorinated biphenyls in water. Journal of Chromatography A.2004,1033 (1):1-8.
[119]Esteve-Turrillas, F. A., Aman, C. S., et al., Microwave-assisted extraction of pyrethroid insecticides from soil. Analytica Chimica Acta.2004,522 (1):73-78.
[120]Fatta-Kassinos, D., Hapeshi, E., et al., Existence of Pharmaceutical Compounds in Tertiary Treated Urban Wastewater that is Utilized for Reuse Applications. Water Resources Management.2011, 25(4):1183-1193.
[121]Hu, J. Y., Chang, H., et al., Detection, Occurrence and Fate of Indirubin in Municipal Sewage Treatment Plants. Environmental Science & Technology.2008,42 (22):8339-8344.
[122]Sui, Q., Huang, J., et al., Occurrence and removal of pharmaceuticals, caffeine and DEET in wastewater treatment plants of Beijing, China. Water Research.2010,44 (2):417-426.
[123]Miao, X. S. and Metcalfe, C. D., Determination of carbamazepine and its metabolites in aqueous samples using liquid chromatography-electrospray tandem mass spectrometry. Analytical Chemistry.2003,75 (15):3731-3738.
[124]Petrovic, M., Hernando, M. D., et al., Liquid chromatography-tandem mass spectrometry for the analysis of pharmaceutical residues in environmental samples:a review. Journal of Chromatography A.2005,1067 (1-2):1-14.
[125]Thomas, P. M. and Foster, G. D., Tracking acidic pharmaceuticals, caffeine, and triclosan through the wastewater treatment process. Environmental Toxicology and Chemistry.2005,24 (1):25-30.
[126]Cirja, M., Ivashechkin, P., et al., Factors affecting the removal of organic micropollutants from wastewater in conventional treatment plants (CTP) and membrane bioreactors (MBR). Reviews in Environmental Science and Biotechnology.2008,7 (1):61-78.
[127]Jones, O. H., Voulvoulis, N., et al., The occurrence and removal of selected pharmaceutical compounds in a sewage treatment works utilising activated sludge treatment. Environmental Pollution. 2007,145 (3):738-744.
[128]Nakada, N., Shinohara, H., et al., Removal of selected pharmaceuticals and personal care products (PPCPs) and endocrine-disrupting chemicals (EDCs) during sand filtration and ozonation at a municipal sewage treatment plant. Water Research.2007,41 (19):4373-4382.
[129]Mcdowell, D. C., Huber, M. M., et al., Ozonation of Carbamazepine in Drinking Water: Identification and Kinetic Study of Major Oxidation Products. Environmental Science & Technology. 2005,39 (20):8014-8022.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |