Environmental fate of chiral pharmaceuticals: Determination, degradation and toxicity

Environmental Chemistry for a Sustainable World

Volumn 2, Issue , 2014, Pages 3-45

  Ribeiro, Ana R ^a,b   Castro, Paula M L ^b   Tiritan, Maria Elizabeth ^a,c  

^a UNIVERSITY INSTITUTE OF HEALTH SCIENCES IUCS   (Portugal)

^b UNIVERSIDADE CATÓLICA PORTUGUESA   (Portugal)

^c UNIVERSITY OF PORTO   (Portugal)

Author keywords

Antidepressants; Atenolol; Beta blockers; Biodegradation; Chiral analysis; Chiral chromatography; Chiral ecotoxicity; Chiral stationary phases; Chiral switching; Enantiomeric fraction; Enantiomers; Enantioselective; Enantioseparation; Enantiospecific toxicity; Fluoxetine; Ibuprofen; Naproxen; Non steroid anti inflammatory drugs; Propranolol; Racemates; Waste water treatment plant

Indexed keywords

AQUATIC ORGANISMS; BIODEGRADATION; BIOLOGY; CHROMATOGRAPHY; DRUG PRODUCTS; ENANTIOMERS; ENANTIOSELECTIVITY; GAS CHROMATOGRAPHY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; LIQUID CHROMATOGRAPHY; POLLUTION; TOXICITY; WASTE DISPOSAL; WASTE TREATMENT; WASTEWATER; WASTEWATER TREATMENT; WATER POLLUTION; WATER TREATMENT; WATER TREATMENT PLANTS;

ANTI-INFLAMMATORY DRUGS; ANTIDEPRESSANTS; ATENOLOL; BETA-BLOCKERS; CHIRAL ANALYSIS; CHIRAL CHROMATOGRAPHY; CHIRAL STATIONARY PHASIS; ECOTOXICITY; ENANTIOMERIC FRACTIONS; ENANTIOSELECTIVE; ENANTIOSEPARATIONS; ENANTIOSPECIFIC; FLUOXETINE; IBUPROFEN; NAPROXENS; PROPRANOLOL; RACEMATES;

STEREOCHEMISTRY;

EID: 84865413679     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-94-007-2439-6_1     Document Type: Chapter

References (177)

1. Aboul-Enein H Y, Ali I (2004) Analysis of the chiral pollutants by chromatography. Toxicol Environ Chem 86(1):1-22
2. Agrawal YK, Patel RN (2005) Chiral chromatographic separation of b-blockers. J Chromatogr B 820(1):23-31
3. Aleksa K, Nava-Ocampo A, Koren G (2009) Detection and quantification of (R) and (S)-dechloroethylifosfamide metabolites in plasma from children by enantioselective LC/MS/MS. Chirality 21(7):674-680
4. Ali I, Gaitonde VD, Aboul-Enein H Y, Hussain A (2009a) Chiral separation of b-adrenergic blockers on CelluCoat column by HPLC. Talanta 78(2):458-463
5. Ali I, Singh P, Aboul-Enein H Y, Sharma B (2009b) Chiral analysis of ibuprofen residues in water and sediment. Anal Lett 42(12):1747-1760
6. Andersson ME, Aslan D, Clarke A, Roeraade J, Hagman G (2003) Evaluation of generic chiral liquid chromatography screens for pharmaceutical analysis. J Chromatogr A 1005(1-2):83-101
7. Ansermot N, Rudaz S, Brawand-Amey M, Fleury-Souverain S, Veuthey J-L, Eap CB (2009) Validation and long-term evaluation of a modified on-line chiral analytical method for therapeutic drug monitoring of (R, S)-methadone in clinical samples. J Chromatogr B 877(23):2301-2307
8. Asher BJ, D'Agostino LA, Way JD, Wong CS, Harynuk JJ (2009) Comparison of peak integration methods for the determination of enantiomeric fraction in environmental samples. Chemosphere 75(8):1042-1048
9. Ates H, Mangelings D, Vander Heyden Y (2008) Chiral separations in polar organic solvent chromatography: updating a screening strategy with new chlorine-containing polysaccharide-based selectors. J Chromatogr B 875(1):57-64
10. Baker GB, Prior TI, Coutts RT (2002) Chirality and drugs used to treat psychiatric disorders. J Psychiatry Neurosci 27(6):401-403
11. Barreiro EJ, Ferreira VF, Costa PRR (1997) Substâncias enantiomericamente puras (SEP): a questão dos fármacos quirais. Quím Nova 20(6):647-656
12. Barreiro JC, Vanzolini KL, Madureira TV, Tiritan ME, Cass QB (2010) A column-switching method for quantification of the enantiomers of omeprazole in native matrices of waste and estuarine water samples. Talanta 82(1):384-391
13. Bartholow M (2010) Top 200 prescription drugs of 2009. Retrieved 27 May 2010
14. Benotti MJ, Brownawell BJ (2009) Microbial degradation of pharmaceuticals in estuarine and coastal seawater. Environ Pollut 157(3):994-1002
15. Benotti MJ, Trenholm RA, Vanderford BJ, Holady JC, Stanford BD, Snyder SA (2009) Pharmaceuticals and endocrine disrupting compounds in U. S. drinking water. Environ Sci Technol 43(3):597-603
16. Bhushan R, Martens J (1997) Direct resolution of enantiomers by impregnated TLC. Biomed Chromatogr 11(5):280-285
17. Bojarski J (2002) Stereoselective chromatography of cardiovascular drugs: an update. J Biochem Biophys Methods 54(1-3):197-220
18. Bonabello A, Galmozzi MR, Canaparo R, Isaia GC, Serpe L, Muntoni E, Zara GP (2003) Dexibuprofen (S (+)-isomer ibuprofen) reduces gastric damage and improves analgesic and antiinflammatory effects in rodents. Anesth Analg 97(2):402-408
19. Bosáková Z, Curínová E, Tesarová E (2005) Comparison of vancomycin-based stationary phases with different chiral selector coverage for enantioselective separation of selected drugs in highperformance liquid chromatography. J Chromatogr A 1088(1-2):94-103
20. Brooks BW, Turner PK, Stanley JK, Weston JJ, Glidewell EA, Foran CM, Slattery M, La Point TW, Huggett DB (2003) Waterborne and sediment toxicity of fluoxetine to select organisms. Chemosphere 52(1):135-142
21. Brooks BW, Chambliss CK, Stanley JK, Ramirez A, Banks KE, Johnson RD, Lewis RJ (2005) Determination of select antidepressants in fish from an effluent-dominated stream. Environ Toxicol Chem 24(2):464-469
22. Buser H-R, Poiger T, Muller MD (1999) Occurrence and environmental behavior of the chiral pharmaceutical drug ibuprofen in surface waters and in wastewater. Environ Sci Technol 33(15):2529-2535
23. Caccamese S, Bianca S, Carter GT (2009) Direct high-performance liquid chromatographic separation of the enantiomers of venlafaxine and 11 analogs using amylose-derived chiral stationary phases. Chirality 21(6):569-577
24. Caldwell J, Hutt AJ, Fournel-Gigleux S (1988) The metabolic chiral inversion and dispositional enantioselectivity of the 2-arylpropionic acids and their biological consequences. Biochem Pharmacol 37(1):105-114
25. Calisto V, Esteves VI (2009) Psychiatric pharmaceuticals in the environment. Chemosphere 77(10):1257-1274
26. Campo VL, Bernardes LSC, Carvalho I (2009) Stereoselectivity in drug metabolism: molecular mechanisms and analytical methods. Curr Drug Metab 10(2):188-205
27. Caner H, Groner E, Levy L, Agranat I (2004) Trends in the development of chiral drugs. Drug Discov Today 9(3):105-110
28. Carvalho PO, Cass QB, Calafatti SA, Contesini FJ, Bizaco R (2006) Review - alternatives for the separation of drug enantiomers: ibuprofen as a model compound. Braz J Chem Eng 23(3):291-300
29. Cass QB and Batigalhia F (2003) Enantiomeric resolution of a series of chiral sulfoxides by highperformance liquid chromatography on polysaccharide-based columns with multimodal elution. J Chromatogr A 987(1-2):445-452
30. Cass QB, Degani ALG, Cassiano NM (2003a) Effects on enantioselectivity by the use of polysaccharide-based columns by multimodal elution. J Liquid Chromatogr Relat Technol 26(13):2083-2101
31. Cass QB, Watanabe CSF, Rabi JA, Bottari PQ, Costa MR, Nascimento RM, Cruz JED, Ronald RC (2003b) Polysaccharide-based chiral phase under polar organic mode of elution in the determination of the enantiomeric purity of emtricitabine an anti-HIV analogue nucleoside. J Pharm Biomed Anal 33(4):581-587
32. Chávez-Flores D, Salvador JM (2009) Commercially viable resolution of ibuprofen. Biotechnol J 4(8):1222-1224
33. Chen C-Y, Shieh W-R, Chen C-S (1992) Clinical implications of using racemic drugs. Clin Res Regul Aff 9(4):247-259
34. Choonara IA, Haynes BP, Cholerton S, Breckenridge AM, Park BK (1986) Enantiomers of warfarin and vitamin K1 metabolism. Br J Clin Pharmacol 22(6):729-732
35. Christen V, Hickmann S, Rechenberg B, Fent K (2010) Highly active human pharmaceuticals in aquatic systems: a concept for their identification based on their mode of action. Aquat Toxicol 96(3):167-181
36. Cleuvers M (2004) Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid. Ecotoxicol Environ Saf 59(3):309-315
37. Cleuvers M (2005) Initial risk assessment for three β-blockers found in the aquatic environment. Chemosphere 59(2):199-205
38. Cooper MJ, Anders MW (1974) Metabolic and pharmacodynamic interactions of enantiomers of propoxyphene and methorphan. Life Sci 15(9):1665-1672
39. Cordato DJ, Mather LE, Herkes GK (2003) Stereochemistry in clinical medicine: a neurological perspective. J Clin Neurosci 10(6):649-654
40. Cox PJ (1994) Drug stereochemistry - analytical methods and pharmacology. Talanta 41(2):343
41. Da Silva Júnior I, De Veredas V, Carpes MJS, Santana CCP (2005) Chromatographic separation of bupivacaine enantiomers by HPLC: parameters estimation of equilibrium and mass transfer under linear conditions. Adsorption 11(2):123-129
42. Daughton CG, Ternes TA (1999) Pharmaceuticals and personal care products in the environment: agents of subtle change? Environ Health Perspect Suppl 107(S6):907-938
43. De Andrés F, Castañeda G, Ríos Á (2009) Use of toxicity assays for enantiomeric discrimination of pharmaceutical substances. Chirality 21(8):751-759
44. Díaz-Cruz MS, García-Galán MJ, Barceló D (2008) Highly sensitive simultaneous determination of sulfonamide antibiotics and one metabolite in environmental waters by liquid chromatographyquadrupole linear ion trap-mass spectrometry. J Chromatogr A 1193(1-2):50-59
45. Eliel EL, Wilen SH (1994) Stereochemistry of organic compounds. Wiley, New York
46. Eljarrat E, Guerra P, Barceló D (2008) Enantiomeric determination of chiral persistent organic pollutants and their metabolites. TrAC Trends Anal Chem 27(10):847-861
47. Escher BI, Bramaz N, Maurer M, Richter M, Sutter D, Känel Cv, Zschokke M (2005) Screening test battery for pharmaceuticals in urine and wastewater. Environ Toxicol Chem 24(3):750-758
48. Farré M, Gros M, Hernández B, Petrovic M, Hancock P, Barceló D (2008) Analysis of biologically active compounds in water by ultra-performance liquid chromatography quadrupole time-offlight mass spectrometry. Rapid Commun Mass Spectrom 22(1):41-51
49. Feitosa-Felizzola J, Temime B, Chiron S (2007) Evaluating on-line solid-phase extraction coupled to liquid chromatography-ion trap mass spectrometry for reliable quantification and confirmation of several classes of antibiotics in urban wastewaters. J Chromatogr A 1164(1-2):95-104
50. Fent K, Weston AA, Caminada D (2006) Ecotoxicology of human pharmaceuticals. Aquat Toxicol 76(2):122-159
51. Fernández C, González-Doncel M, Pro J, Carbonell G, Tarazona JV (2010) Occurrence of pharmaceutically active compounds in surface waters of the henares-jarama-tajo river system (madrid, spain) and a potential risk characterization. Sci Total Environ 408(3):543-551
52. Flaherty CM, Dodson SI (2005) Effects of pharmaceuticals on Daphnia survival, growth, and reproduction. Chemosphere 61(2):200-207
53. Flippin JL, Huggett D, Foran CM (2007) Changes in the timing of reproduction following chronic exposure to ibuprofen in Japanese medaka, Oryzias latipes. Aquat Toxicol 81(1):73-78
54. Fong PP (1998) Zebra Mussel Spawning Is Induced in Low Concentrations of Putative Serotonin Reuptake Inhibitors. The Biol Bull 194:143-149
55. Fong PP, Molnar N (2008) Norfluoxetine induces spawning and parturition in estuarine and freshwater bivalves. Bull Environ Contam Toxicol 81(6):535-538
56. Fono LJ, Sedlak DL (2005) Use of the chiral pharmaceutical propranolol to identify sewage discharges into surface waters. Environ Sci Technol 39(23):9244-9252
57. Fono LJ, Kolodziej EP, Sedlak DL (2006) Attenuation of wastewater-derived contaminants in an effluent-dominated river. Environ Sci Technol 40(23):7257-7262
58. Foran CM, Weston J, Slattery M, Brooks BW, Huggett DB (2004) Reproductive assessment of Japanese medaka (oryzias latipes) following a four-week fluoxetine (SSRI) exposure. Arch Environ Contam Toxicol 46(4):511-517
59. Francotte ER (2001) Enantioselective chromatography as a powerful alternative for the preparation of drug enantiomers. J Chromatogr A 906(1-2):379-397
60. Francotte E (2009) Enantioselective chromatography: from its emergence to its successful implementation in the pharmaceutical environment. CHIMIA Int J Chem 63:867-871
61. Franz PM, Anliker SL, Callaghan JT, DeSante KA, Dhahir PH, Nelson RL, Rubin A (1990) Disposition in humans of racemic picenadol, an opioid analgesic. Drug Metab Dispos 18(6):968-973
62. Gatti G, Bonomi I, Marchiselli R, Fattore C, Spina E, Scordo G, Pacifici R, Perucca E (2003) Improved enantioselective assay for the determination of fluoxetine and norfluoxetine enantiomers in human plasma by liquid chromatography. J Chromatogr B 784(2):375-383
63. Gonçalves RF, Lauretti GR, Mattos ALd (2003) Comparative study between 0.5% Bupivacaine and 0.5% enantiomeric mixture of bupivacaine (S75-R25) in epidural anesthesia. Rev Bras Anestesiol 53(2):169-176
64. González S, Petrovic M, Barceló D (2007) Advanced liquid chromatography-mass spectrometry (LC-MS) methods applied to wastewater removal and the fate of surfactants in the environment. TrAC Trends Anal Chem 26(2):116-124
65. Gomes RF, Cassiano NM, Pedrazzoli Jr. J, Cass QB (2010) Two-dimensional chromatography method applied to the enantiomeric determination of lansoprazole in human plasma by direct sample injection. Chirality 22(1):35-41
66. Görög S (2007) The changing face of pharmaceutical analysis. TrAC Trends Anal Chem 26(1):12-17
67. Gros M, Petrovic M, Barceló D (2006) 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 70(4):678-690
68. Gübitz G, Schmid MG (2004) Recent advances in chiral separation principles in capillary electrophoresis and capillary electrochromatography. Electrophoresis 25(23):3981-3996
69. Haginaka J (2008) Recent progresses in protein-based chiral stationary phases for enantioseparations in liquid chromatography. J Chromatogr B 875(1):12-19
70. Ha PTT, Hoogmartens J, Van Schepdael A (2006) Recent advances in pharmaceutical applications of chiral capillary electrophoresis. J Pharm Biomed Anal 41(1):1-11
71. Hansen LK, Frost PC, Larson JH, Metcalfe CD (2008) Poor elemental food quality reduces the toxicity of fluoxetine on Daphnia magna. Aquat Toxicol 86(1):99-103
72. Hashim NH, Shafie S, Khan SJ (2010) Enantiomeric fraction as an indicator of pharmaceutical biotransformation during wastewater treatment and in the environment - a review. Environ Technol 31(12):1349-1370
73. Heckmann L-H, Callaghan A, Hooper HL, Connon R, Hutchinson TH, Maund SJ, Sibly RM (2007) Chronic toxicity of ibuprofen to daphnia magna: effects on life history traits and population dynamics. Toxicol Lett 172(3):137-145
74. Hefnawy MM, Sultan MA, Al-Shehri MM (2007) HPLC separation technique for analysis of bufuralol enantiomers in plasma and pharmaceutical formulations using a vancomycin chiral stationary phase and UV detection. J Chromatogr B 856(1-2):328-336
75. Henry TB, Black MC (2008) Acute and chronic toxicity of fluoxetine (selective serotonin reuptake inhibitor) in western mosquitofish. Arch Environ Contam Toxicol 54(2):325-330
76. Henry ME, Schmidt ME, Hennen J, Villafuerte RA, Butman ML, Tran P, Kerner LT, Cohen B, Renshaw PF (2005) A comparison of brain and serum pharmacokinetics of R-fluoxetine and racemic fluoxetine: a 19-F MRS study. Neuropsychopharmacology 30(8):1576-1583
77. Hijosa-Valsero M, Matamoros V, Martín-Villacorta J, Bécares E, Bayona JM (2010) Assessment of full-scale natural systems for the removal of PPCPs from wastewater in small communities. Water Res 44(5):1429-1439
78. Huang YF, Pryor ME, Mather LE, Veering BT (1998) Cardiovascular and central nervous system effects of intravenous levobupivacaine and bupivacaine in sheep. Anesth Analg 86(4):797-804
79. Huggett DB, Brooks BW, Peterson B, Foran CM, Schlenk D (2002) Toxicity of select beta adrenergic receptor-blocking pharmaceuticals (B-blockers) on aquatic organisms. Arch Environ Contam Toxicol 43(2):229-235
80. Huggett DB, Khan IA, Foran CM, Schlenk D (2003) Determination of beta-adrenergic receptor blocking pharmaceuticals in United States wastewater effluent. Environ Pollut 121(2):199-205
81. Hühnerfuss H, Shah MR (2009) Enantioselective chromatography-a powerful tool for the discrimination of biotic and abiotic transformation processes of chiral environmental pollutants. J Chromatogr A 1216(3):481-502
82. Huq F (2007) Molecular modelling analysis of the metabolism of methadone. Asian J Biochem 2(1):19-30
83. Hutt AJ (1998) Drug chirality and its pharmacological consequences. In: Smith HJ, Williams' H (eds) Introduction to the principles of Drug design and action, 3rd edn. Elsevier, Amsterdam
84. Hutt AJ, Valentová J (2003) The chiral switch: the development of single enantiomer drugs from racemates. Acta Fac Pharm Univ Comen 50:7-23
85. IMS Health report (2006) http://www.imshealth.com
86. Isidori M, Lavorgna M, Nardelli A, Parrella A, Previtera L, Rubino M (2005) Ecotoxicity of naproxen and its phototransformation products. Sci Total Environ 348(1-3):93-101
87. Izake EL (2007) Chiral discrimination and enantioselective analysis of drugs: an overview. J Pharm Sci 96(7):1659-1676
88. Jain AK, Michael R, Ryan JR, McMahon FG (1984) Antihypertensive and biochemical effects of indacrinone enantiomers. Pharmacotherapy 4(5):278-283
89. Jiang Z, Schurig V (2008) Existence of a low isoenantioselective temperature in complexation gas chromatography: profound change of enantioselectivity of a nickel (II) chiral selector either bonded to, or dissolved in, poly (dimethylsiloxane). J Chromatogr A 1186(1-2):262-270
90. Johnson DJ, Sanderson H, Brain RA, Wilson CJ, Bestari KT, Solomon KR (2005) Exposure assessment and microcosm fate of selected selective serotonin reuptake inhibitors. Regul Toxicol Pharmacol 42(3):313-323
91. Jones OAH, Voulvoulis N, Lester JN (2007) The occurrence and removal of selected pharmaceutical compounds in a sewage treatment works utilising activated sludge treatment. Environ Pollut 145(3):738-744
92. Kasprzyk-Hordern B, Kondakal VVR, Baker DR (2010) Enantiomeric analysis of drugs of abuse in wastewater by chiral liquid chromatography coupled with tandem mass spectrometry. J Chromatogr A 1217(27):4575-4586
93. Khetan SK, Collins TJ (2007) Human pharmaceuticals in the aquatic environment: a challenge to green chemisty. Chem Rev 107(6):2319-2364
94. Kim J-W, Ishibashi H, Yamauchi R, Ichikawa N, Takao Y, Hirano M, Koga M, Arizono K (2009) Acute toxicity of pharmaceutical and personal care products on freshwater crustacean (Thamnocephalus platyurus) and fish (Oryzias latipes). J Toxicol Sci 34(2):227-232
95. Koch S, Perry KW, Nelson DL, Conway RG, Threlkeld PG, Bymaster FP (2002) R-fluoxetine increases extracellular DA, NE, as well as 5-HT in Rat prefrontal cortex and hypothalamus: an in vivo microdialysis and receptor binding study. Neuropsychopharmacology 27(6):949-959
96. Kot-Wasik A, Debska J, Namiesnik J (2007) Analytical techniques in studies of the environmental fate of pharmaceuticals and personal-care products. TrAC Trends Anal Chem 26(6):557-568
97. Lamas JP, Salgado-Petinal C, García-Jares C, Llompart M, Cela R, Gómez M (2004) Solid-phase microextraction-gas chromatography-mass spectrometry for the analysis of selective serotonin reuptake inhibitors in environmental water. J Chromatogr A 1046(1-2):241-247
98. Lämmerhofer M (2010) Chiral recognition by enantioselective liquid chromatography: mechanisms and modern chiral stationary phases. J Chromatogr A 1217(6):814-856
99. Li L, Zhou S, Jin L, Zhang C, Liu W (2010) Enantiomeric separation of organophosphorus pesticides by high-performance liquid chromatography, gas chromatography and capillary electrophoresis and their applications to environmental fate and toxicity assays. J Chromatogr B 878(17-18):1264-1276
100. Lima VLE (1997) Drugs and chirality: a brief overview. Quím Nova 20(6):657-663
101. Lister A, Regan C, Van Zwol J, Van Der Kraak G (2009) Inhibition of egg production in zebrafish by fluoxetine and municipal effluents: a mechanistic evaluation. Aquat Toxicol 95(4):320-329
102. Liu Q-T, Cumming RI, Sharpe AD (2009) Photo-induced environmental depletion processes of β-blockers in river waters. Photochem Photobiol Sci 8(6):768-777
103. MacLeod SL, Wong CS (2010) Loadings, trends, comparisons, and fate of achiral and chiral pharmaceuticals in wastewaters from urban tertiary and rural aerated lagoon treatments. Water Res 44(2):533-544
104. MacLeod SL, Sudhir P, Wong CS (2007) Stereoisomer analysis of wastewater-derived b-blockers, selective serotonin re-uptake inhibitors, and salbutamol by high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 1170(1-2):23-33
105. Madureira TV, Barreiro JC, Rocha MJ, Cass QB, Tiritan ME (2009) Pharmaceutical trace analysis in aqueous environmental matrices by liquid chromatography-ion trap tandem mass spectrometry. J Chromatogr A 1216(42):7033-7042
106. Maftouh M, Granier-Loyaux C, Chavana E, Marini J, Pradines A, Heyden YV, Picard C (2005) Screening approach for chiral separation of pharmaceuticals: part III. Supercritical fluid chromatography for analysis and purification in drug discovery. J Chromatogr A 1088(1-2):67-81
107. Mannschreck A, Kiesswetter R, von Angerer E (2007) Unequal activities of enantiomers via biological receptors: examples of chiral drug, pesticide, and fragrance molecules. J Chem Educ 84(12):2012-2018
108. Montanari MLC, Cass QB, Leitão A, Andricopulo AD and Montanari CA (2006) The role of molecular interaction fields on enantioselective and nonselective separation of chiral sulfoxides. J Chromatogr A 1121(1):64-75
109. Marco-Urrea E, Pérez-Trujillo M, Blánquez P, Vicent T, Caminal G (2010) Biodegradation of the analgesic naproxen by Trametes versicolor and identification of intermediates using HPLC-DAD-MS and NMR. Bioresour Technol 101(7):2159-2166
110. Mascolo G, Balest L, Cassano D, Laera G, Lopez A, Pollice A, Salerno C (2010) Biodegradability of pharmaceutical industrial wastewater and formation of recalcitrant organic compounds during aerobic biological treatment. Bioresour Technol 101(8):2585-2591
111. Matamoros V, Hijosa M, Bayona JM (2009) Assessment of the pharmaceutical active compounds removal in wastewater treatment systems at enantiomeric level. Ibuprofen and naproxen. Chemosphere 75(2):200-205
112. Maurer M, Escher BI, Richle P, Schaffner C, Alder AC (2007) Elimination of b-blockers in sewage treatment plants. Water Res 41(7):1614-1622
113. Mayer JM, Testa B (1997) Pharmacodynamics, pharmacokinetics and toxicity of ibuprofen enantiomers. Drugs Future 22:1347-1366
114. McConathy J, Owens MJ (2003) Stereochemistry in drug action. Prim Care J Clin Psychiatry Companion 5(2):70-73
115. Moss GP (1996) Basic terminology of stereochemistry (IUPAC recommendations 1996). Pure Appl Chem 68(12):2193-2222
116. Müller TA, Kohler HPE (2004) Chirality of pollutants-effects on metabolism and fate. Appl Microbiol Biotechnol 64(3):300-316
117. Munoz-Bellido JL, Munoz-Criado S, Garcìa-Rodrìguez JA (2000) Antimicrobial activity of psychotropic drugs: Selective serotonin reuptake inhibitors. Int J Antimicrob Agents 14(3):177-180
118. Musson SE, Campo P, Tolaymat T, Suidan M, Townsend TG (2010) Assessment of the anaerobic degradation of six active pharmaceutical ingredients. Sci Total Environ 408(9):2068-2074
119. Nakamura Y, Yamamoto H, Sekizawa J, Kondo T, Hirai N, Tatarazako N (2008) The effects of pH on fluoxetine in Japanese medaka (Oryzias latipes): acute toxicity in fish larvae and bioaccumulation in juvenile fish. Chemosphere 70(5):865-873
120. Nalecz-Jawecki G (2007) Evaluation of the in vitro biotransformation of fluoxetine with HPLC, mass spectrometry and ecotoxicological tests. Chemosphere 70(1):29-35
121. Niessen WMA (2003) Progress in liquid chromatography-mass spectrometry instrumentation and its impact on high-throughput screening. J Chromatogr A 1000(1-2):413-436
122. Nikolai LN, McClure EL, MacLeod SL, Wong CS (2006) Stereoisomer quantification of the - blocker drugs atenolol, metoprolol, and propranolol in wastewaters by chiral high-performance liquid chromatography-tandem mass spectrometry. J Chromatogr A 1131(1-2):103-109
123. Orlando RM, Cardoso Filho N, Gil ES, Stringhetta JPS (2007) The pharmaceutical importance of chiral drugs. Rev Electrôn Farm IV (1): 8-14
124. Owen SF, Giltrow E, Huggett DB, Hutchinson TH, Saye J, Winter MJ, Sumpter JP (2007) Comparative physiology, pharmacology and toxicology of β-blockers: mammals versus fish. Aquat Toxicol 82(3):145-162
125. Owen SF, Huggett DB, Hutchinson TH, Hetheridge MJ, Kinter LB, Ericson JF, Sumpter JP (2009) Uptake of propranolol, a cardiovascular pharmaceutical, from water into fish plasma and its effects on growth and organ biometry. Aquat Toxicol 93(4):217-224
126. Paterson G, Metcalfe CD (2008) Uptake and depuration of the anti-depressant fluoxetine by the Japanese medaka (Oryzias latipes). Chemosphere 74(1):125-130
127. Pavlinov SA, Belolipetskaya VG, Piotrovskii VK, Metelitsa VI, Filatova NP, Bochkareva EV (1990) Enantiomers of propranolol in the blood of patients with cardiovascular diseases during long-term therapy. Pharm Chem J 24(1):17-19
128. Pérez S, Barceló D (2008) Applications of LC-MS to quantitation and evaluation of the environmental fate of chiral drugs and their metabolites. TrAC Trends Anal Chem 27(10):836-846
129. Perrin C, Matthijs N, Mangelings D, Granier-Loyaux C, Maftouh M, Massart DL, Vander Heyden Y (2002a) Screening approach for chiral separation of pharmaceuticals: part II. Reversed-phase liquid chromatography. J Chromatogr A 966(1-2):119-134
130. Perrin C, Vu VA, Matthijs N, Maftouh M, Massart DL, Vander Heyden Y (2002b) Screening approach for chiral separation of pharmaceuticals: part I. Normal-phase liquid chromatography. J Chromatogr A 947(1):69-83
131. Pirkle WH, Pochapsky TC (1989) Considerations of chiral recognition relevant to the liquid chromatographic separation of enantiomers. Chem Rev 89(2):347-362
132. Pirzada Z, Personick M, Biba M, Gong X, Zhou L, Schafer W, Roussel C, Welch CJ (2010) Systematic evaluation of new chiral stationary phases for supercritical fluid chromatography using a standard racemate library. J Chromatogr A 1217(7):1134-1138
133. Ranta V-P, Toropainen E, Talvitie A, Auriola S, Urtti A (2002) Simultaneous determination of eight β-blockers by gradient high-performance liquid chromatography with combined ultraviolet and fluorescence detection in corneal permeability studies in vitro. J Chromatogr B Analyt Technol Biomed Life Sci 772(1):81-87
134. Reungoat J, Macova M, Escher BI, Carswell S, Mueller JF, Keller J (2010) Removal of micropollutants and reduction of biological activity in a full scale reclamation plant using ozonation and activated carbon filtration. Water Res 44(2):625-637
135. Richardson SD (2006) Environmental mass spectrometry: emerging contaminants and current issues. Anal Chem 78(12):4021-4045
136. Rosal R, Rodríguez A, Perdigón-Melón JA, Petre A, García-Calvo E, Gómez MJ, Agüera A, Fernández-Alba AR (2010) Occurrence of emerging pollutants in urban wastewater and their removal through biological treatment followed by ozonation. Water Res 44(2):578-588
137. Rykowska I, Wasiak W (2009) Recent advances in gas chromatography for solid and liquid stationary phases containing metal ions. J Chromatogr A 1216(10):1713-1722
138. Sánchez-Argüello P, Fernández C, Tarazona JV (2009) Assessing the effects of fluoxetine on Physa acuta (Gastropoda, Pulmonata) and Chironomus riparius (Insecta, Diptera) using a two-species water-sediment test. Sci Total Environ 407(6):1937-1946
139. Sancho R, Minguillón C (2009) The chromatographic separation of enantiomers through nanoscale design. Chem Soc Rev 38(3):797-805
140. Santos AR, Pinheiro AC, Sodero ACR, Cunha AS, Padilha MC, Sousa PM, Fontes SP (2007) Atropisomerism: the effect of the axial chirality in bioactive compounds. Quím Nova 30(1):125-135
141. Santos LHM L M, Araújo AN, Fachini A, Pena A, Delerue-Matos C, Montenegro MCB S M (2010) Ecotoxicological aspects related to the presence of pharmaceuticals in the aquatic environment. J Hazard Mater 175(1-3):45-95
142. Schnell S, Kawano A, Porte C, Lee LEJ, Bols NC (2008) Effects of ibuprofen on the viability and proliferation of rainbow trout liver cell lines and potential problems and interactions in effects assessment. Environ Toxicol 24(2):157-165
143. Scriba GKE (2003) Pharmaceutical and biomedical applications of chiral capillary electrophoresis and capillary electrochromatography: An update. Electrophoresis 24(15):2409-2421
144. Schurig V (2001) Separation of enantiomers by gas chromatography. J Chromatogr A 906(1-2):275-299
145. Silva BJG, Lanças FM, Queiroz MEC (2009) Determination of fluoxetine and norfluoxetine enantiomers in human plasma by polypyrrole-coated capillary in-tube solid-phase microextraction coupled with liquid chromatography-fluorescence detection. J Chromatogr A 1216(49):8590-8597
146. Singh AK, Kedor-Hackmann ÉRM, Santoro MIRM (2006) Applied chiral phase liquid chromatography in enantiomeric separation of cardiovascular drugs. Braz J Pharm Sci 42(4):553-566
147. Sipma J, Osuna B, Collado N, Monclús H, Ferrero G, Comas J, Rodriguez-Roda I (2010) Comparison of removal of pharmaceuticals in MBR and activated sludge systems. Desalination 250(2):653-659
148. Smith SW (2009) Chiral toxicology: it's the same thing only different. Toxicol Sci 110(1):4-30
149. Somogyi A, Bochner F, Foster D (2004) Inside the isomers: the tale of chiral switches. Aus Prescriber 27(2):47-49
150. Sousa EP, Tiritan ME, Oliveira RV, Afonso CMM, Cass QB, Pinto MMM (2004) Enantiomeric resolution of kielcorin derivatives by HPLC on polysaccharide stationary phases using multimodal elution. Chirality 16(5):279-285
151. Stanley JK, Ramirez AJ, Chambliss CK, Brooks BW (2007) Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate. Chemosphere 69(1):9-16
152. Stefan R-I, van Staden JF, Aboul-Enein HY (2000a) Amperometric biosensors/sequential injection analysis system for simultaneous determination of S- and R-captopril. Biosens Bioelectron 15(1-2):1-5
153. Stefan R-I, van Staden JF, Aboul-Enein HY (2000b) Simultaneous detection of S and R captopril using sequential injection analysis. Talanta 51(5):969-975
154. Steiner TJ, Ahmed F, Findley LJ, MacGregor EA, Wilkinson M (1998) S-fluoxetine in the prophylaxis of migraine: a phase II double-blind randomized placebo-controlled study. Cephalalgia 18(5):283-286
155. Stevens JC, Wrighton SA (1993) Interaction of the enantiomers of fluoxetine and norfluoxetine with human liver cytochromes P450. J Pharmacol Exp Ther 266(2):964-971
156. Stringer JL (2006) Basic concepts in pharmacology: a student's survival guide, 3rd edn. McGraw Hill, New York
157. Taylor LT (2009) Supercritical fluid chromatography for the 21st century. J Supercrit Fluids 47(3):566-573
158. Ternes TA (1998) Occurrence of drugs in German sewage treatment plants and rivers. Water Res 32(11):3245-3260
159. Toreson H, Eriksson BM (1997) Liquid chromatographic determination of fluvastatin and its enantiomers in blood plasma by automated solid-phase extraction. Chromatographia 45:29-34
160. Trautwein C, Kümmerer K, Metzger JW (2008) Aerobic biodegradability of the calcium channel antagonist verapamil and identification of a microbial dead-end transformation product studied by LC-MS/MS. Chemosphere 72(3):442-450
161. Trenholm RA, Vanderford BJ, Holady JC, Rexing DJ, Snyder SA (2006) Broad range analysis of endocrine disruptors and pharmaceuticals using gas chromatography and liquid chromatography tandem mass spectrometry. Chemosphere 65(11):1990-1998
162. Tucker GT (2000) Chiral switches. Lancet 355(9209):1085-1087
163. Unceta N, Barrondo S, de Azúa IR, Gómez-Caballero A, Goicolea MA, Sallés J, Barrio RJ (2007) Determination of fluoxetine, norfluoxetine and their enantiomers in rat plasma and brain samples by liquid chromatography with fluorescence detection. J Chromatogr B 852(1-2):519-528
164. Union, E. P.a.t. C.o.t. E (2006). Regulation (EC) No 1907/2006 of the European Parliament and of the Council of 18 December 2006 concerning the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH), establishing a European Chemicals Agency, amending Directive 1999/45/EC and repealing Council Regulation (EEC) No 793/93 and Commission Regulation (EC) No 1488/94 as well as Council Directive 76/769/EEC and Commission Directives 91/155/EEC, 93/67/EEC, 93/105/EC and 2000/21/EC Official Journal of the European Union: 396/391-396/849
165. Vanderford BJ, Snyder SA (2006) Analysis of pharmaceuticals in water by isotope dilution liquid chromatography/tandem mass spectrometry. Environ Sci Technol 40(23):7312-7320
166. Wang SH, Liang ZH, Zeng S (2007) Monitoring release of ketoprofen enantiomers from biodegradable poly (D, L-lactide-co-glycolide) injectable implants. Int J Pharm 337(1-2):102-108
167. Westerhoff P, Yoon Y, Snyder S, Wert E (2005) Fate of endocrine-disruptor, pharmaceutical, and personal care product chemicals during simulated drinking water treatment processes. Environ Sci Technol 39(17):6649-6663
168. Winder VL, Sapozhnikova Y, Pennington PL, Wirth EF (2009) Effects of fluoxetine exposure on serotonin-related activity in the sheepshead minnow (Cyprinodon variegatus) using LC/MS/MS detection and quantitation. Comp Biochem Physiol C Toxicol Pharmacol 149(4):559-565
169. Winkler M, Lawrence JR, Neu TR (2001) Selective degradation of ibuprofen and clofibric acid in two model river biofilm systems. Water Res 35(13):3197-3205
170. Winter MJ, Lillicrap AD, Caunter JE, Schaffner C, Alder AC, Ramil M, Ternes TA, Giltrow E, Sumpter JP, Hutchinson TH (2008) Defining the chronic impacts of atenolol on embryo-larval development and reproduction in the fathead minnow (Pimephales promelas). Aquat Toxicol 86(3):361-369
171. Wistuba D (2010) Chiral silica-based monoliths in chromatography and capillary electrochromatography. J Chromatogr A 1217(7):941-952
172. Wistuba D, Schurig V (2000) Enantiomer separation of chiral pharmaceuticals by capillary electrochromatography. J Chromatogr A 875(1-2):255-276
173. Wong CS, Garrison AW (2000) Enantiomer separation of polychlorinated biphenyl atropisomers and polychlorinated biphenyl retention behavior on modified cyclodextrin capillary gas chromatography columns. J Chromatogr A 866(2):213-220
174. Zhang H, Spiteller M, Guenther K, Boehmler G, Zuehlke S (2009) Degradation of a chiral nonylphenol isomer in two agricultural soils. Environ Pollut 157(6):1904-1910
175. Zhang T, Nguyen D, Franco P (2010) Reversed-phase screening strategies for liquid chromatography on polysaccharide-derived chiral stationary phases. J Chromatogr A 1217(7):1048-1055
176. Zhou J, Yang Y-W, Wei F, Ping-dong W (2007) Comparison of the performance of chiral stationary phase for separation of fluoxetine enantiomers. J Zhejiang Univ Sci B 8(1):56-59
177. Zorita S, Mårtensson L, Mathiasson L (2009) Occurrence and removal of pharmaceuticals in a municipal sewage treatment system in the south of Sweden. Sci Total Environ 407(8):2760-2770 Lobore essi. Re volore et, sum nonsectet wis dolorti scilit, sum in vel ulluptat ecte etuer sequamcommod