Vol.:(0123456789) 1 3 Archives of Environmental Contamination and Toxicology https://doi.org/10.1007/s00244-019-00630-z MINI-REVIEW Environmental Transformation of Pharmaceutical Formulations: A Scientifc Review Gordana Švonja Parezanović 1  · Mladena Lalic‑Popovic 1  · Svetlana Golocorbin‑Kon 1  · Velibor Vasovic 2  · Boris Milijašević 2  · Hani Al‑Salami 3  · Momir Mikov 2 Received: 5 September 2018 / Accepted: 15 April 2019 © Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Environmental pollution caused by pharmaceuticals and their transformation products (TPs) has become an increasingly important concern, due to the increased use of pharmaceutical formulations exposed to environmental change. Considerable concerns have been raised regarding potential toxic efects of the transformation products of pharmaceutical formulations on human health. Environmental risk assessments are mostly based on one active component, which causes diferent ecotoxi- cological efects, albeit the particular component is present in the environment as a part of a multicomponent mixture with diferent pharmaceuticals and excipients. The purpose of this review was to present the insight and new knowledge recently obtained by studies on the risk of pharmaceutical formulations, including all contained excipients, pharmaceuticals, and their transformation products exposed to the environment. Numerous studies have shown that the level of pharmaceuticals in the environment is below toxic concentration; however, long exposure to very low concentrations can still lead to harmful concentrations in biota. Accordingly, the fndings of this study are expected to highlight the existing issues of the efect of pharmaceutical formulations to the environment, including TPs, and help to determine future research directions towards accumulating the data and improving ecological risk assessment. Environmental pollution involves the release of pharma- ceuticals into water supplies, the atmosphere, and the soil causing detrimental efects on the environment. Recently, the environmental pollution caused by pharmaceuticals and their transformation products (TPs) has become a global concern, due to the continual rise in human population and the increasing use of pharmaceutical formulations. Pharma- ceuticals may have long half-lives in the environment, so they can accumulate, and adversely afect human health and the environment due to their properties and toxicity even at very low concentrations. Considerable concerns have been raised regarding potential efects of the transformation of pharmaceutical formulations on human health. It has been discovered that not only active drug components are sig- nifcant in terms of evaluation of ecological risk but also those compounds created as a consequence of their TPs and mixture of diferent excipients contained in the pharmaceuti- cal formulation. Many studies have reviewed that pharma- ceutical products and their TPs in nature can lead to vari- ous undesired consequences, with toxicological efects on human health and ecosystems (Bartrons and Penuelas 2017; Daughton 2016; Snyder and Benotti 2010). Despite the rap- idly growing number of studies and reports on the presence of pharmaceuticals in the environment, the number of stud- ies on identifcation, quantifcation, and characterisation of TPs of pharmaceuticals and excipients is still low. Advanced analytical methods have a signifcant role in the analysis of environmental samples with the goal of confrming their degree of pollution. Advantage is given to quick, simple, and economically proftable methods that allow for obtaining reliable results of a greater number of samples, ofering a quick estimate of exposure of population to pharmaceuticals and their TPs (Gracia-Lor et al. 2010; Negreira et al. 2015). Many studies of toxicity have shown that some pharmaceu- ticals are found in the environment at concentrations well * Gordana Švonja Parezanović gordana.svonja-parezanovic@mf.uns.ac.rs 1 Department of Pharmacy, Faculty of Medicine, University Novi Sad, Novi Sad, Serbia 2 Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University Novi Sad, Novi Sad, Serbia 3 Biotechnology and Drug Development Research Lab, School of Pharmacy, Curtin Health Innovation Research Institute, Curtin University, Perth, WA, Australia