The Journey of Human Drugs from Their
Design at the Bench to Their Fate in Crops
Nicola Montemurro, Juan Manuel Peña-Herrera, Antoni Ginebreda,
Peter Eichhorn, and Sandra Pérez
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2 Drug Discovery and Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3 Physico-chemical Space of Small-Molecule Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
4 Absorption, Distribution, Metabolism, and Excretion (ADME) . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5 Environmental Regulatory Perspective in the European Union . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
6 Presence of Pharmaceuticals in Wastewater . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
7 Pharmaceuticals in Crops Irrigated with Treated Wastewater . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8 Uptake, Distribution, and Metabolism of PhACs in Crops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
9 Presence of Drugs in Earthworms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
10 Drugs in Constructed Wetlands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
11 Analysis of Drugs and Their Metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Abstract The topic of this book is dedicated to the analysis, fate, metabolism,
effects, and remediation of pharmaceutically active compounds in water-soil-biota
systems. While the majority of readers are likely to already have a broad understanding of potential entry points, flows, transformation pathways, and temporary
and permanent sinks of drugs in the environment, the objectives of this first chapter
are fourfold: (a) to provide a concise overview of the journey a drug takes from its
inception at the laboratory bench to the desk of the reviewer at the regulatory agency;
(b) to understand the biological and physiological processes a drug undergoes from
administration to humans – or to the animal in case of veterinary medicines – to their
excretion and ultimately discharge into wastes; (c) to describe the physico-chemical
space small-molecule drugs reside in as this characteristic largely governs their later
environmental fate; (d) to review their presence, fate, and metabolism in crops and
N. Montemurro (*), J. M. Peña-Herrera, A. Ginebreda, P. Eichhorn, and S. Pérez
ENFOCHEM, Department of Environmental Chemistry, Institute of Environmental Assessment
and Water Research, Barcelona, Spain
e-mail: nmoqam@cid.csic.es
Sandra Pérez Solsona, Nicola Montemurro, Serge Chiron, and Damià Barceló (eds.),
Interaction and Fate of Pharmaceuticals in Soil-Crop Systems: The Impact of
Reclaimed Wastewater, Hdb Env Chem (2021) 103: 3–32, DOI 10.1007/698_2020_643,
© Springer Nature Switzerland AG 2020, Published online: 21 August 2020
3
Design at the Bench to Their Fate in Crops
Nicola Montemurro, Juan Manuel Peña-Herrera, Antoni Ginebreda,
Peter Eichhorn, and Sandra Pérez
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
2 Drug Discovery and Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
3 Physico-chemical Space of Small-Molecule Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
4 Absorption, Distribution, Metabolism, and Excretion (ADME) . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
5 Environmental Regulatory Perspective in the European Union . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
6 Presence of Pharmaceuticals in Wastewater . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
7 Pharmaceuticals in Crops Irrigated with Treated Wastewater . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
8 Uptake, Distribution, and Metabolism of PhACs in Crops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
9 Presence of Drugs in Earthworms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
10 Drugs in Constructed Wetlands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
11 Analysis of Drugs and Their Metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Abstract The topic of this book is dedicated to the analysis, fate, metabolism,
effects, and remediation of pharmaceutically active compounds in water-soil-biota
systems. While the majority of readers are likely to already have a broad understanding of potential entry points, flows, transformation pathways, and temporary
and permanent sinks of drugs in the environment, the objectives of this first chapter
are fourfold: (a) to provide a concise overview of the journey a drug takes from its
inception at the laboratory bench to the desk of the reviewer at the regulatory agency;
(b) to understand the biological and physiological processes a drug undergoes from
administration to humans – or to the animal in case of veterinary medicines – to their
excretion and ultimately discharge into wastes; (c) to describe the physico-chemical
space small-molecule drugs reside in as this characteristic largely governs their later
environmental fate; (d) to review their presence, fate, and metabolism in crops and
N. Montemurro (*), J. M. Peña-Herrera, A. Ginebreda, P. Eichhorn, and S. Pérez
ENFOCHEM, Department of Environmental Chemistry, Institute of Environmental Assessment
and Water Research, Barcelona, Spain
e-mail: nmoqam@cid.csic.es
Sandra Pérez Solsona, Nicola Montemurro, Serge Chiron, and Damià Barceló (eds.),
Interaction and Fate of Pharmaceuticals in Soil-Crop Systems: The Impact of
Reclaimed Wastewater, Hdb Env Chem (2021) 103: 3–32, DOI 10.1007/698_2020_643,
© Springer Nature Switzerland AG 2020, Published online: 21 August 2020
3