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In no event shall the Royal Society of Chemistry be held responsible for any errors or omissions in this Accepted Manuscript or any consequences arising from the use of any information it contains. www.rsc.org/greenchem Page 1 of 21 PleaseGreen do not Chemistry adjust margins Green Chemistry PERSPECTIVE Perspectives on the replacement of harmful organic solvents in analytical methodologies: A framework toward the Received 00th January 20xx, Accepted 00th January 20xx implementation of a novel generation of eco-friendly alternatives a,b, c b DOI: 10.1039/x0xx00000x Francisco Pena-Pereira *, Adam Kloskowski and Jacek Namieśnik www.rsc.org/ Volatile organic solvents derived from non-renewable fossil feedstocks are commonplace in analytical laboratories. In spite of their convenient performance in countless unit operations, their environmental, health and safety issues represent a major area of concern. The progressive replacement of organic solvents obtained from fossil resources by eco-friendly Manuscript alternatives would involve remarkable advances within the framework of green analytical chemistry, while avoiding future uncertainties regarding forthcoming regulations. This perspective tackles the problem of organic solvent use in analytical methodologies, providing relevant information for solvent selection and identifying a range of solvents derived from natural and/or renewable resources, namely bio-based molecular solvents, ionic liquids composed wholly of biomaterials, and natural deep eutectic mixtures, that could potentially be exploited toward advanced, more benign, analytical methodologies. In addition, physicochemical properties are provided, and a number of challenging aspects to be considered on the implementation of eco-friendly alternatives are evaluated. toward sustainable chemical processes. In fact, several Introduction principles of green chemistry3–6 and green analytical chemistry7–9 (Figure 1) directly or indirectly refer to this Millions of litres of organic solvents are used each year in problematic issue. Thus, the 5th principle of green chemistry analytical laboratories, which poses potential risk to human specifically refers to the removal of solvents from chemical health and significantly contribute to the generation of laboratories whenever possible or their replacement by safer hazardous wastes, constituting an important source of volatile Accepted 1 alternatives. In addition, other green chemistry principles can organic compounds (VOCs) emission. The solvent also be of relevance when considering solvents, such as waste consumption depends to a high extent on a set of parameters, prevention (1st), use and generation of substances that possess namely the type and concentration levels of the analytes to be little or no toxicity (3rd), design of safer, non-persistent and determined, the sample composition, the sample preparation biodegradable chemicals (4th and 10th), use of innocuous technique (whenever required) and the analytical auxiliary substances and renewable feedstocks (5th and 7th), instrumentation employed. A rapid glance over recommended and inherently safer chemistry for accident prevention (12th). methods of analysis shows that several environmentally A large variety of solvents, mainly derived from fossil fuels, are unfriendly organic solvents are frequently required in the routinely used in different steps of the analytical process. determination of a wide range of target compounds. Some Preparation of solutions, extraction and enrichment of target examples are summarized on Table 1. This has been precisely compounds, sample clean up, solvent exchange, sample pinpointed by Anastas, who considers that “it is an preservation, dilution, glassware cleaning, liquid desorption, unfortunate irony that environmental analytical methods often derivatisation, and analytical separation and detection are contribute to further environmental problems through the 2 among the operations in which solvents are exploited in chemicals used in the analysis”. In this regard, the use of analytical chemistry. A progressive replacement of petroleum- harmful solvents in analytical methodologies can represent an Chemistry based solvents by efficient and more sustainable alternatives issue of environmental, health and safety concern. would importantly reduce the current dependence on The search for safer solvents is identified as a clear priority conventional organic solvents in analytical laboratories. Green This journal is © The Royal Society of Chemistry 2015 Green Chem., 2015, 00, 1-3 | 1 Please do not adjust margins PleaseGreen do not Chemistry adjust margins Page 2 of 21 Green Chemistry PERSPECTIVE Table 1 Solvents used in some approved analytical methodologies Analytical Method ID Solventsa Sample preparation Target analytes Samples technique EPA Method acetonitrile and methylene chloride LLE HPLC- PAHs drinking water 550 UV/FLD EPA Method acetonitrile, methanol and methylene chloride SPE HPLC- PAHs drinking water 550.1 UV/FLD EPA Method acetone, cyclohexane, hexane, isooctane, SPE/LLE/CLLE/Soxhlet GC-MS chlorinated biphenyl water, soil, 1668A methanol, methylene chloride, nonane and extraction congeners sediment and toluene tissue Manuscript EPA Method acetone, hexane, methanol, methylene chloride, LLE/CLLE/Soxhlet GC-MS steroids and water, soil, 1698 pyridine and toluene extraction-clean up- hormones sediment and derivatisation bio-solids EPA Method acetone, benzene, ethyl acetate, ethyl ether, derivatisation-LLE-clean GC-ECD acrylamide water 8032A methanol and methylene chloride up EPA Method acetone, acetonitrile, cyclohexane, ethyl acetate, LLE/CLLE/SPE/Soxhlet GC- organophosphorus liquid and solid 8141B hexane, isooctane, isopropanol, methanol, methyl extraction/PLE/MAE/UA FPD/NPD compounds samples tert-butyl-ether, methylene chloride, isopropanol, E-clean up tetrahydrofuran and toluene APPA/AWWA benzene, glycerol, isobutanol and methanol LLE UV-vis phosphorus water /WEF 4500 APPA/AWWA chloroform or methylene chloride LLE UV-vis phenols water /WEF 5530 APPA/AWWA benzene, chloroform and methanol LLE UV-vis anionic surfactants water /WEF 5540 Accepted APPA/AWWA methyl isobutyl ketone LLE FAAS metals water /WEF 3110 aNote that not all the solvents listed may be needed for a single analysis as the list includes all the solvents required to carry out the different sample preparation techniques. CLLE, continuous liquid-liquid extraction; ECD, electron capture detection; FLD, fluorescence detection; FAAS, flame atomic absorption spectrometry; FPD, flame photometric detection; GC, gas chromatography; HPLC, high performance liquid chromatography; LLE, liquid-liquid extraction; MAE, microwave-assisted extraction; MS, mass spectrometry; NPD, nitrogen-phosphorus detection; PAHs, polyaromatic hydrocarbons; PLE, pressurised liquid extraction; SPE, solid-phase extraction; UAE, ultrasound-assisted extraction; UV, ultraviolet detection Francisco Pena-Pereira (born Adam Kloskowski (born 1974) 1981) received his PhD (2009) in graduated from the Gdaosk Chemistry from the University of University of Technology with an Vigo (Spain). He then joined the MSc in Chemical Technology in Centre for Environmental and 2000. In 2002 obtained licentiate Marine Studies (CESAM) & degree at Royal University of University of Aveiro (Portugal) as a Technology (KTH) in Stockholm. Chemistry post-doctoral fellow (2011–2013). He obtained his PhD in 2005. His At present, he is focused on the major research interests include development and application of the development of new environmentally sustainable analytical procedures for analytical methodologies at the determining polar organic Gdaosk University of Technology compounds in various matrixes, (Poland). electroanalytical methods as well as physicochemical properties of ionic liquids. Green This journal is © The Royal Society of Chemistry 2015 Green Chem., 2015, 00, 1-3 | 2 Please do not adjust margins Page 3 of 21 PleaseGreen do not Chemistry adjust margins Green Chemistry PERSPECTIVE Regarding the use of organic solvents in the analytical process, The use of large volumes of harmful solvents in analytical sample preparation and analytical separation are of special separations is also a matter of concern, especially in the case importance due to the type and volumes of solvents used, of liquid chromatography. It has been estimated that a which highly contribute to the generation of hazardous waste. continuously operated analytical liquid chromatograph would Sample preparation is commonly the most polluting step of result in an annual waste generation of around 500 litres the analytical process. Conventional sample preparation working under typical conditions.18