Comprehensive analysis of a widely pharmaceutical, furosemide, and its degradation products in aquatic systems: Occurrence, fate, and ecotoxicity.

Many pharmaceutical compounds end up in the environment due to incomplete removal by wastewater treatment plants (WWTPs). Some compounds are sometimes present in significant concentrations and therefore represent a risk to the aquatic environment. Furosemide is one of the most widely used drugs in the world. Considered as an essential drug by the World Health Organization, this powerful loop diuretic is used extensively to treat hypertension, heart and kidney failure and many other purposes. However, this important consumption also results in a significant release of furosemide in wastewater and in the receiving environment where concentrations of a few hundred ng/L to several thousand have been found in the literature, making furosemide a compound of great concern. Also, during its transport in wastewater systems and WWTPs, furosemide can be degraded by various processes resulting in the production of more than 74 by-products. Furosemide may therefore present a significant risk to ecosystem health due not only to its direct cytotoxic, genotoxic and hepatotoxic effects in animals, but also indirectly through its transformation products, which are poorly characterized. Many articles classify furosemide as a priority pollutant according to its occurrence in the environment, its persistence, its elimination by WWTPs, its toxicity and ecotoxicity. Here, we present a state-of-the-art review of this emerging pollutant of interest, tracking it, from its consumption to its fate in the aquatic environment. Discussion points include the occurrence of furosemide in various matrices, the efficiency of many processes for the degradation of furosemide, the subsequent production of degradation products following these treatments, as well as their toxicity.

Occurrence and fate of an emerging drug pollutant and its by-products during conventional and advanced wastewater treatment: Case study of furosemide.

Conventional wastewater treatment systems are not designed to remove pharmaceutical compounds from wastewater. These compounds can be degraded into many other transformation products which are hardly, if at all, studied. In this context, we studied the occurrence and degradation of furosemide, a very frequently detected diuretic, along with its known degradation products in several types of wastewater. Influent and effluent from the Seine-Centre Wastewater Treatment Plant (WWTP) (Paris, France) as well as outlet of residential care homes (Dordogne, France) were analyzed by Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) to quantify furosemide and its known degradation products, saluamine and pyridinium of furosemide. Oxidation experiments (chlorination, ozonation and UV photolysis with hydrogen peroxide) were then performed on furosemide solutions and on water from residential care facilities to study the degradation of furosemide by potential advanced processes, and also to identify unknown oxidation products by high-resolution mass spectrometry. Furosemide was well degraded in Seine-Centre WWTP (>75%) but did not increase the concentrations of its main degradation products. Saluamine and pyridinium of furosemide were already present at similar concentrations to furosemide in the raw wastewater (∼2.5-3.5 µg.L-1), and their removal in the WWTPs were very high (>80%). Despite their removal, the three compounds remained present in treated wastewater effluents at concentrations of hundreds of nanograms per liter. Chlorination degraded furosemide without pyridinium production unlike the other two processes. Chlorination and ozonation were also effective for the removal of furosemide and pyridinium in residential care home water, but they resulted in the production of saluamine. To our knowledge this is the first evidence of saluamine and pyridinium of furosemide in real water samples in either the particulate or dissolved phase.