Towards the design of active pharmaceutical ingredients mineralizing readily in the environment

Puhlmann, Neele; Mols, Renate; Olsson, Oliver; Slootweg, J. Chris; Kümmerer, Klaus

doi:10.1039/d1gc01048d

Cited by 24 publications

(25 citation statements)

References 86 publications

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“…The GREENER concept, based on “benign by design”, 19 illustrates that decision making in drug discovery and development can be beneficial for both human and environmental health when some prerequisites are met. 23 The overarching principle “good practice for patients” holds that protecting environmental health should not compromise patient health. Because of the intimate link between human and environmental health, it is imperative that environmental considerations be increasingly embedded within this overarching principle.…”

Section: Way Forward: Greener Pharmaceuticalsmentioning

confidence: 99%

“…Examples of APIs that are completely (bio)degradable in the environment are summarized elsewhere. 23 , 26 The desired properties for improved environmental degradation do not have to interfere with the API’s administration to patients. 23 To identify environmental (bio)degradability in the drug discovery process, medium-throughput screening assays are needed.…”

Section: Way Forward: Greener Pharmaceuticalsmentioning

confidence: 99%

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GREENER Pharmaceuticals for More Sustainable Healthcare

Moermond

Puhlmann

Brown

et al. 2022

Environ. Sci. Technol. Lett.

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Medicines are essential to human health but can also impact the aquatic and terrestrial environment after use by patients and release via excreta into wastewater. We highlight the need for a GREENER approach to identify and meet important environmental criteria, which will help reduce the impact of medicinal residues on the environment. These criteria include effect reduction by avoiding nontarget effects or undesirable moieties, exposure reduction via lower emissions or environmental (bio)degradability, no PBT (persistent, bioaccumulative, and toxic) substances, and risk mitigation. With all of these criteria, however, patient health is of primary importance as medicines are required to be safe and efficacious for treating diseases. We discuss the feasibility of including these criteria for green by design active pharmaceutical ingredients in the process of drug discovery and development and which tools or assays are needed to accomplish this. The integrated GREENER approach can be used to accelerate discussions about future innovations in drug discovery and development.

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Section: Way Forward: Greener Pharmaceuticalsmentioning

confidence: 99%

Section: Way Forward: Greener Pharmaceuticalsmentioning

confidence: 99%

GREENER Pharmaceuticals for More Sustainable Healthcare

Moermond

Puhlmann

Brown

et al. 2022

Environ. Sci. Technol. Lett.

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“…Then, the leads are submitted to extensive testing and optimization, including pharmacokinetic properties (absorption, distribution, metabolism, excretion (ADME)), reduced toxicity, and chemical stability. In silico tools are essential to support these optimization cycles. , At the end of this process, the most promising and optimized candidates are selected and submitted to preclinical trials. , This procedure from the field of drug discovery can be adapted for the purpose of nontargeted de novo BbD if considerations like environmental mineralization and (eco)toxicity are implemented in the screening and optimization process …”

Section: Different Approaches Of the Bbd Conceptmentioning

confidence: 99%

“…49,51 This procedure from the field of drug discovery can be adapted for the purpose of nontargeted de novo BbD if considerations like environmental mineralization and (eco)toxicity are implemented in the screening and optimization process. 52 Targeted de Novo Design. The targeted de novo design approach combines low molecular weight fragments concerning their function to more complex molecules.…”

Section: ■ Different Approaches Of the Bbd Conceptmentioning

confidence: 99%

Toward Application and Implementation of in Silico Tools and Workflows within Benign by Design Approaches

Lorenz¹,

Amsel²,

Puhlmann

et al. 2021

ACS Sustainable Chem. Eng.

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To avoid adverse side effects of chemicals, pharmaceuticals, and their transformation products (TPs) in the environment, substances should be designed to fully mineralize in the environment at their end-of-life while ensuring a degree of stability as needed for their application. These considerations should be implemented at the very beginning of chemical’s and pharmaceutical’s design (Benign by Design, BbD) to meet requirements set by planetary boundaries and upcoming legal frameworks (e.g., “Chemicals Strategy for Sustainability towards a Toxic-Free Environment” by the European Commission (EC)). In silico tools are already being implemented in the drug discovery process and the assessment of chemicals and pharmaceuticals. The advantage of which is avoiding or at least minimizing animal testing and chemical waste due to experimental testing as well as reducing the time to market. However, in the literature, there are just a few examples of how in silico tools could be implemented in the BbD process. Therefore, this study suggests a workflow supporting practitioners designing new environmentally mineralizing chemicals and pharmaceuticals. This would also result in a much faster and less expensive process than starting with repetitive synthesis and subsequent experimental testing to improve the compounds’ properties.

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“…Another drawback of target screening is overlooking contaminant metabolites and TPs that can, in some cases, retain biological activity and/or be more abundant and harmful than their parent compounds [ 9 , 10 ]. In fact, the path from discharge to complete mineralization is rather long and complex, and it was demonstrated that incomplete mineralization of one parent compound yields several TPs [ 11 ]. Concern about their occurrence is gaining more and more scientific attention; for instance, O-desmethyl venlafaxine was already included in the Water Watch List under the Water Framework Directive ( , accessed on 1 February 2022).…”

Section: Introductionmentioning

confidence: 99%

Use of Passive and Grab Sampling and High-Resolution Mass Spectrometry for Non-Targeted Analysis of Emerging Contaminants and Their Semi-Quantification in Water

et al. 2022

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Different groups of organic micropollutants including pharmaceuticals and pesticides have emerged in the environment in the last years, resulting in a rise in environmental and human health risks. In order to face up and evaluate these risks, there is an increasing need to assess their occurrence in the environment. Therefore, many studies in the past couple of decades were focused on the improvements in organic micropollutants’ extraction efficiency from the different environmental matrices, as well as their mass spectrometry detection parameters and acquisition modes. This paper presents different sampling methodologies and high-resolution mass spectrometry-based non-target screening workflows for the identification of pharmaceuticals, pesticides, and their transformation products in different kinds of water (domestic wastewater and river water). Identification confidence was increased including retention time prediction in the workflow. The applied methodology, using a passive sampling technique, allowed for the identification of 85 and 47 contaminants in the wastewater effluent and river water, respectively. Finally, contaminants’ prioritization was performed through semi-quantification in grab samples as a fundamental step for monitoring schemes.

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Towards the design of active pharmaceutical ingredients mineralizing readily in the environment

Abstract: Active pharmaceutical ingredients (APIs), their metabolites and transformation products (TPs) occur globally in the environment. They risk the environmental and human health. These alarming circumstances highlight the strong need for...

Cited by 24 publications

References 86 publications

GREENER Pharmaceuticals for More Sustainable Healthcare

GREENER Pharmaceuticals for More Sustainable Healthcare

Toward Application and Implementation of in Silico Tools and Workflows within Benign by Design Approaches

Use of Passive and Grab Sampling and High-Resolution Mass Spectrometry for Non-Targeted Analysis of Emerging Contaminants and Their Semi-Quantification in Water

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