The results of an inter-laboratory comparison exercise to determine cytostatic anticancer drug residues in surface water, hospital wastewater and wastewater treatment plant effluent are reported. To obtain a critical number of participants, an invitation was sent out to potential laboratories identified to have the necessary knowledge and instrumentation. Nine laboratories worldwide confirmed their participation in the exercise. The compounds selected (based on the extent of use and laboratories capabilities) included cyclophosphamide, ifosfamide, 5-fluorouracil, gemcitabine, etoposide, methotrexate and cisplatinum. Samples of spiked waste (hospital and wastewater treatment plant effluent) and surface water, and additional non-spiked hospital wastewater, were prepared by the organising laboratory (Jožef Stefan Institute) and sent out to each participant partner for analysis. All analytical methods included solid phase extraction (SPE) and the use of surrogate/internal standards for quantification. Chemical analysis was performed using either liquid or gas chromatography mass (MS) or tandem mass (MS/MS) spectrometry. Cisplatinum was determined using inductively coupled plasma mass spectrometry (ICP-MS). A required minimum contribution of five laboratories meant that only cyclophosphamide, ifosfamide, methotrexate and etoposide could be included in the statistical evaluation. z-score and Q test revealed 3 and 4 outliers using classical and robust approach, respectively. The smallest absolute differences between the spiked values and the measured values were observed in the surface water matrix. The highest within-laboratory repeatability was observed for methotrexate in all three matrices (CV ≤ 12 %). Overall, inter-laboratory reproducibility was poor for all compounds and matrices (CV 27-143 %) with the only exception being methotrexate measured in the spiked hospital wastewater (CV = 8 %). Random and total errors were identified by means of Youden plots.

Catalan Institute for Water Research Emili Grahit 101 Edifici H2O Parc Científic i Tecnològic 17003 Girona Spain

CEH Lancaster Lancaster Environment Centre Library Avenue Bailrigg Lancaster UK

Central Wastewater Treatment Plant Ljubljana VO KA Cesta v prod 100 1000 Ljubljana Slovenia

Eurofins Omegam H J E Wenckebachweg 120 1114 AD Amsterdam Duivendrecht The Netherlands

Faculty of Science RECETOX Masaryk University Kamenice 5 Brno Czech Republic

Institute of Oncology Zaloška cesta 2 1000 Ljubljana Slovenia

International Postgraduate School Jožef Stefan Jamova 39 Ljubljana Slovenia

IWW Water Centre Moritzstrasse 26 45476 Muelheim Germany

Jožef Stefan Institute Jamova 39 1000 Ljubljana Slovenia

National University of Singapore 21 Lower Kent Ridge Rd Singapore Singapore

Wastewater Treatment Plant Domžale Kamnik Študljanska cesta 91 1230 Domžale Slovenia

Water and Soil Quality Research Group Institute of Environmental Assessment and Water Research Jordi Girona 18 08034 Barcelona Spain

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