22. Lee D, Choi K (2019) Comparison of regulatory frameworks of environmental risk assessments for human pharmaceuticals in EU, USA, and Canada. Sci Total Environ 671:1026–1035
23. Agency EM (2019) Draft guideline on the environmental risk assessment of medicinal
products for human use – Revision 1 EMEA/CHMP/SWP/4447/00 Rev. 1. Committee for
Medicinal Products for Human Use (CHMP)
24. aus der Beek T, Weber FA, Bergmann A, Hickmann S, Ebert I, Hein A, Küster A (2016)
Pharmaceuticals in the environment – global occurrences and perspectives. Environ Toxicol
Chem 35(4):823–835
25. Schwarzenbach RP, Escher BI, Fenner K, Hofstetter TB, Johnson CA, Von Gunten U, Wehrli
B (2006) The challenge of micropollutants in aquatic systems. Science 313(5790):1072–1077
26. Heberer T (2002) Occurrence, fate, and removal of pharmaceutical residues in the aquatic
environment: a review of recent research data. Toxicol Lett 131(1):5–17
27. Behera SK, Kim HW, Oh J-E, Park H-S (2011) Occurrence and removal of antibiotics,
hormones and several other pharmaceuticals in wastewater treatment plants of the largest
industrial city of Korea. Sci Total Environ 409(20):4351–4360. https://doi.org/10.1016/j.
scitotenv.2011.07.015
28. Evgenidou EN, Konstantinou IK, Lambropoulou DA (2015) Occurrence and removal of
transformation products of PPCPs and illicit drugs in wastewaters: a review. Sci Total Environ
505:905–926
29. Bottoni P, Caroli S, Caracciolo AB (2010) Pharmaceuticals as priority water contaminants.
Toxicol Environ Chem 92(3):549–565
30. Lapworth D, Baran N, Stuart M, Ward R (2012) Emerging organic contaminants in groundwater: a review of sources, fate and occurrence. Environ Pollut 163:287–303
31. Patrolecco L, Ademollo N, Grenni P, Tolomei A, Caracciolo AB, Capri S (2013) Simultaneous determination of human pharmaceuticals in water samples by solid phase extraction and
HPLC with UV-fluorescence detection. Microchem J 107:165–171
32. Patel M, Kumar R, Kishor K, Mlsna T, Pittman Jr CU, Mohan D (2019) Pharmaceuticals of
emerging concern in aquatic systems: chemistry, occurrence, effects, and removal methods.
Chem Rev 119(6):3510–3673
33. Lopez-Serna R, Petrovic M, Barcelo D (2012) Direct analysis of pharmaceuticals, their
metabolites and transformation products in environmental waters using on-line TurboFlow
chromatography-liquid chromatography-tandem mass spectrometry. J Chromatogr A
1252:115–129. https://doi.org/10.1016/j.chroma.2012.06.078
34. Gros M, Petrovic M, Barcelo D (2008) Tracing pharmaceutical residues of different therapeutic classes in environmental waters by using liquid chromatography/quadrupole-linear ion trap
mass spectrometry and automated library searching. Anal Chem 81(3):898–912
35. Oulton RL, Kohn T, Cwiertny DM (2010) Pharmaceuticals and personal care products in
effluent matrices: a survey of transformation and removal during wastewater treatment and
implications for wastewater management. J Environ Monit 12(11):1956–1978. https://doi.org/
10.1039/c0em00068j
36. Mandaric L, Kalogianni E, Skoulikidis N, Petrovic M, Sabater S (2019) Contamination
patterns and attenuation of pharmaceuticals in a temporary Mediterranean river. Sci Total
Environ 647:561–569. https://doi.org/10.1016/j.scitotenv.2018.07.308
37. Jelic A, Gros M, Ginebreda A, Cespedes-Sánchez R, Ventura F, Petrovic M, Barcelo D (2011)
Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during
wastewater treatment. Water Res 45(3):1165–1176. https://doi.org/10.1016/j.watres.2010.11.
010
38. Verlicchi P, Al Aukidy M, Zambello E (2012) Occurrence of pharmaceutical compounds in
urban wastewater: removal, mass load and environmental risk after a secondary treatment – a
review. Sci Total Environ 429:123–155
39. Rivera-Jaimes JA, Postigo C, Melgoza-Alemán RM, Aceña J, Barceló D, López de Alda M
(2018) Study of pharmaceuticals in surface and wastewater from Cuernavaca, Morelos,
The Journey of Human Drugs from Their Design at the Bench to Their Fate in Crops
27
23. Agency EM (2019) Draft guideline on the environmental risk assessment of medicinal
products for human use – Revision 1 EMEA/CHMP/SWP/4447/00 Rev. 1. Committee for
Medicinal Products for Human Use (CHMP)
24. aus der Beek T, Weber FA, Bergmann A, Hickmann S, Ebert I, Hein A, Küster A (2016)
Pharmaceuticals in the environment – global occurrences and perspectives. Environ Toxicol
Chem 35(4):823–835
25. Schwarzenbach RP, Escher BI, Fenner K, Hofstetter TB, Johnson CA, Von Gunten U, Wehrli
B (2006) The challenge of micropollutants in aquatic systems. Science 313(5790):1072–1077
26. Heberer T (2002) Occurrence, fate, and removal of pharmaceutical residues in the aquatic
environment: a review of recent research data. Toxicol Lett 131(1):5–17
27. Behera SK, Kim HW, Oh J-E, Park H-S (2011) Occurrence and removal of antibiotics,
hormones and several other pharmaceuticals in wastewater treatment plants of the largest
industrial city of Korea. Sci Total Environ 409(20):4351–4360. https://doi.org/10.1016/j.
scitotenv.2011.07.015
28. Evgenidou EN, Konstantinou IK, Lambropoulou DA (2015) Occurrence and removal of
transformation products of PPCPs and illicit drugs in wastewaters: a review. Sci Total Environ
505:905–926
29. Bottoni P, Caroli S, Caracciolo AB (2010) Pharmaceuticals as priority water contaminants.
Toxicol Environ Chem 92(3):549–565
30. Lapworth D, Baran N, Stuart M, Ward R (2012) Emerging organic contaminants in groundwater: a review of sources, fate and occurrence. Environ Pollut 163:287–303
31. Patrolecco L, Ademollo N, Grenni P, Tolomei A, Caracciolo AB, Capri S (2013) Simultaneous determination of human pharmaceuticals in water samples by solid phase extraction and
HPLC with UV-fluorescence detection. Microchem J 107:165–171
32. Patel M, Kumar R, Kishor K, Mlsna T, Pittman Jr CU, Mohan D (2019) Pharmaceuticals of
emerging concern in aquatic systems: chemistry, occurrence, effects, and removal methods.
Chem Rev 119(6):3510–3673
33. Lopez-Serna R, Petrovic M, Barcelo D (2012) Direct analysis of pharmaceuticals, their
metabolites and transformation products in environmental waters using on-line TurboFlow
chromatography-liquid chromatography-tandem mass spectrometry. J Chromatogr A
1252:115–129. https://doi.org/10.1016/j.chroma.2012.06.078
34. Gros M, Petrovic M, Barcelo D (2008) Tracing pharmaceutical residues of different therapeutic classes in environmental waters by using liquid chromatography/quadrupole-linear ion trap
mass spectrometry and automated library searching. Anal Chem 81(3):898–912
35. Oulton RL, Kohn T, Cwiertny DM (2010) Pharmaceuticals and personal care products in
effluent matrices: a survey of transformation and removal during wastewater treatment and
implications for wastewater management. J Environ Monit 12(11):1956–1978. https://doi.org/
10.1039/c0em00068j
36. Mandaric L, Kalogianni E, Skoulikidis N, Petrovic M, Sabater S (2019) Contamination
patterns and attenuation of pharmaceuticals in a temporary Mediterranean river. Sci Total
Environ 647:561–569. https://doi.org/10.1016/j.scitotenv.2018.07.308
37. Jelic A, Gros M, Ginebreda A, Cespedes-Sánchez R, Ventura F, Petrovic M, Barcelo D (2011)
Occurrence, partition and removal of pharmaceuticals in sewage water and sludge during
wastewater treatment. Water Res 45(3):1165–1176. https://doi.org/10.1016/j.watres.2010.11.
010
38. Verlicchi P, Al Aukidy M, Zambello E (2012) Occurrence of pharmaceutical compounds in
urban wastewater: removal, mass load and environmental risk after a secondary treatment – a
review. Sci Total Environ 429:123–155
39. Rivera-Jaimes JA, Postigo C, Melgoza-Alemán RM, Aceña J, Barceló D, López de Alda M
(2018) Study of pharmaceuticals in surface and wastewater from Cuernavaca, Morelos,
The Journey of Human Drugs from Their Design at the Bench to Their Fate in Crops
27