Search

Temporary rivers become dependent on wastewater effluent for base flows, which severely impacts river ecosystems through exposure to elevated levels of nutrients, dissolved organic matter, and organic micropollutants. However, biodegradation processes occurring in these rivers can be enhanced by wastewater bacteria/biofilms. Here, we evaluated the attenuation of pharmaceuticals and their human metabolites performing retrospective analysis of 120 compounds (drugs, their metabolites and transformation products) in mesocosm channels loaded with wastewater effluents twice a week for a period of 31 days. Eighteen human metabolites and seven biotransformation products were identified with high level of confidence. Compounds were classified into five categories. Type-A: recalcitrant drugs and metabolites (diclofenac, carbamazepine and venlafaxine); Type-B: degradable drugs forming transformation products (TPs) (atenolol, sitagliptin, and valsartan); Type-C: drugs for which no known human metabolites or TPs were detected (atorvastatin, azithromycin, citalopram, clarithromycin, diltiazem, eprosartan, fluconazole, ketoprofen, lamotrigine, lormetazepam, metformin, telmisartan, and trimethoprim); Type-D: recalcitrant drug metabolites (4-hydroxy omeprazole sulfide, erythro/threo-hydrobupropion, and zolpidem carboxylic acid); Type-E: unstable metabolites whose parent drug was not detectable (norcocaine, benzolylecgonine, and erythromycin A enol ether). Noteworthy was the valsartan acid formation from valsartan with transient formation of TP-336., This study has been financially supported by the EU through the PRIMA project (INWAT 201980E121). This work was supported by the Spanish Ministry of Science and Innovation (Project CEX2018-000794-S). The authors also acknowledge SCIEX for providing the loan instrument LC/HRMS QTOF X500R. The EU is not liable for any use that may be made of the information contained therein.

The objective of this introductory chapter is to provide basic knowledge to environmental scientists involved in studying occurrence, fate, and effects of pharmaceuticals with respect to aspects pertaining to modern Drug Discovery and Development. It provides a concise picture of fundamental terms used in pharmacokinetics and drug metabolism, and describes the role of physicochemical properties as the key determinants of absorption, distribution, metabolism, and excretion (ADME) of drugs. The role of drug metabolism in Drug Discovery is highlighted and the most common drug-metabolizing enzymes are portrayed. In the last part of this chapter, the position of major pharmaceutical companies on the presence of pharmaceuticals in the environment and their view on possible adverse effects on aquatic organisms and human health are reviewed.

Objectives: Toxic oil syndrome (TOS) is a disease that appeared in Spain in 1981. Epidemiological work traced the origin to the ingestion of aniline-adulterated rapeseed oil, fraudulently marketed and sold as edible oil. It affected more than 20,000 people with over 400 deaths in the first 2 years. In 2001 evidence was presented that genetic factors could play a role in the susceptibility of individuals to the disease. Thus, a prospective study on the differences in gene expression in sera between control versus TOS-affected populations, both originally exposed to the toxic oil, was undertaken in our laboratory. Methods: Differential protein expression was analyzed by two-dimensional electrophoresis (2-DE). Problems related with serum analysis by 2-DE were addressed to improve protein detection in the gel images. Three new commercial systems for albumin depletion were tested to optimize the detection of minor proteins. The use of nonionic reductants or the presence of thiourea in the gels, were also tested. Results: From the resulting optimized images, a group of 329 major gel spots was located, matched and compared with serum samples. Thirty-five of these protein spots were found to be under- or over-expressed in TOS patients (threefold increase or decrease). Proteins in these spots were identified by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) peptide map fingerprinting and database search. Several haptoglobin (Hp) isoforms were found to be differentially expressed, showing expression phenotypes that could be related with TOS. Resolution of the homologous α-1s and α-1f chains, with a mass difference of only 0.043 Da, was obtained after guanidation of the protein with O-methylisourea. We applied this procedure to the study of the distribution of the Hp alleles HP 2, HP 1s and HP 1f in control versus TOS-affected populations. The MALDI-TOF proteotyping method was validated by a parallel analysis of the serum samples by 2-DE. Conclusions: Data obtained from 54 TOS cases and 48 controls indicate significant differences in the distribution of Hp phenotypes in the two populations. Haptoglobin phenotypes have been reported to have biological and clinical consequences and have been described as risk factors for several diseases. Consequently, it was concluded that haptoglobin polymorphism could play a role in TOS. © 2010 Elsevier Ireland Ltd. All Rights Reserved., This work was supported by WHO projects EU/03/016989 and EU 05/025039.

8 pages, 6 figures, 2 tables.-- PMID: 17996876 [PubMed].-- Printed version published on Dec 21, 2007., This study aimed to develop and optimize a method for the extraction and analysis of moenomycin antibiotics (a.k.a. flavomycin) in corn-based feed premix and in chicken litter. Moenomycin-A was isolated from chicken litter using pressurized liquid extraction followed by a solid-phase extraction (SPE) clean-up step. The highly lipophilic nature of moenomycin necessitated the use of the less hydrophobic sorbent, C4-based SPE cartridge, and a higher temperature elution solvent, methanol at 50ºC, in order to obtain satisfactory percent recoveries. After clean-up, the sample was analyzed by liquid chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS). Various reversed-phase columns were examined, including C18, CN, perfluorinated C6, and a porous graphitic carbon. The set of conditions that gave the highest separation efficiency while still maintaining symmetrical peak shape was the C18 column using the H2O + 0.3% HCOOH and acetonitrile mobile phase., This material is based upon work supported by the National Science Foundation under grant no. 0233700. Any opinions, findings, and conclusions or recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the National Science Foundation. S.P. acknowledges a post-doctoral fellowship from the Spanish Ministry of Education, Culture and Science (EX2003-0687).

Publisher Summary This chapter focuses on the environmental processes. Low concentrations at environmentally relevant levels are used for the examination of primary biodegradability, whereas higher amounts of the parent compounds are selected when to identify the unknown metabolites. Linear alkylbenzene sulfonates (LASs) are one of the best-studied organic substances produced on an industrial scale with respect to environmental behavior. The gap in the understanding of the metabolic pathway of LAS and the occurrence and fate of the aerobic degradative products in the environment was bridged by utilizing a fixed-bed bioreactor (FBBR). The chapter discusses two major factors that affect the environmental relevance of such screening test results and limit their extrapolation to real-world settings: (1) standard screening tests do not accurately simulate the physical, chemical, and biological conditions found in environmental systems and (2) the tests ignore several compartments such as sediments, soils, and water (groundwater, estuaries, and oceans).