title: Environmental exposure to pharmaceuticals: A new technique for trace analysis of carbamazepine and its metabolites in human urine.
abstract: Pharmaceutically active compounds are taken up and accumulate in crops irrigated with treated wastewater. This raises the concern of chronic human exposure to pharmaceuticals via food consumption. Thus, there is a need to develop a reliable technique to detect and quantify pharmaceuticals at environmentally relevant concentrations in human biological matrices, particularly urine. In this study, we focus on carbamazepine, an antiepileptic drug and recalcitrant compound that is taken up by crops-making it an excellent model compound for this study. This paper presents a new analytical technique enabling quantification of trace concentrations of carbamazepine and its metabolites in the urine of individuals who have been environmentally exposed. Sample preparation included extraction with acetonitrile followed by clean-up through mixed-mode ion-exchange cartridges and analysis using LC/MS/MS. This technique, which was validated for a wide range of concentrations (5-2000 ng L(-1)), exhibits low limits of quantification (3.0-7.2 ng L(-1)), acceptable recovery levels (70-120%), and low relative standard deviation (<20%). Unlike currently available methods for the analysis of water or treated wastewater that require large volumes (up to 1 L), the new method uses only 10 mL of urine. Moreover, relative to available methods for carbamazepine detection in the urine of individuals who are chronically treated with this drug, the limit of quantification values with our method are six orders of magnitude lower. The newly developed method has been successfully applied for the quantification of carbamazepine and its metabolites in the urine of healthy people exposed to this pharmaceutical through their diet. Our analytical protocol can provide the scientific community and stakeholders with real data for risk assessments and the design of policies ensuring safe use of wastewater for crop irrigation.
authors.affiliation: Department of Soil and Water Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel; The Hebrew University Center of Excellence in Agriculture and Environmental Health, P.O. Box 12, Rehovot, 76100, Israel; Faculty of Fisheries and Protection of Waters, University of South Bohemia in Ceske Budejovice, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Ganna
authors.initials: G
authors.lastname: Fedorova
authors.affiliation: The Interdepartmental Equipment Facility, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel.
authors.forename: Julius
authors.initials: J
authors.lastname: Ben Ari
authors.affiliation: Department of Soil and Water Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel; The Hebrew University Center of Excellence in Agriculture and Environmental Health, P.O. Box 12, Rehovot, 76100, Israel.
authors.forename: Galit
authors.initials: G
authors.lastname: Tadmor
authors.affiliation: The Hebrew University Center of Excellence in Agriculture and Environmental Health, P.O. Box 12, Rehovot, 76100, Israel; Braun School of Public Health and Community Medicine of the Faculty of Medicine, Hadassah/Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ora
authors.initials: O
authors.lastname: Paltiel
authors.affiliation: Department of Soil and Water Sciences, Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, 76100, Israel; The Hebrew University Center of Excellence in Agriculture and Environmental Health, P.O. Box 12, Rehovot, 76100, Israel. Electronic address: benny.chefetz@mail.huji.ac.il.
authors.forename: Benny
authors.initials: B
authors.lastname: Chefetz
mesh_terms: D002220:Carbamazepine / Q000652:urine*; D002853:Chromatography, Liquid; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D006801:Humans; D053719:Tandem Mass Spectrometry; D062065:Wastewater; D014874:Water Pollutants, Chemical / Q000652:urine*
chemical_list: D002220:Carbamazepine; D062065:Wastewater; D014874:Water Pollutants, Chemical
keywords: Exposure; LC/MS/MS; Recovery; Treated wastewater