Please cite this article in press as: I. Tarcomnicu, et al., Talanta (2010), doi:10.1016/j.talanta.2010.10.045 ARTICLE IN PRESS G Model TAL-11666; No. of Pages 9 Talanta xxx (2010) xxx–xxx Contents lists available at ScienceDirect Talanta journal homepage: www.elsevier.com/locate/talanta Simultaneous determination of 15 top-prescribed pharmaceuticals and their metabolites in influent wastewater by reversed-phase liquid chromatography coupled to tandem mass spectrometry Isabela Tarcomnicu a , Alexander L.N. van Nuijs a,∗ , Ward Simons a , Lieven Bervoets b , Ronny Blust b , Philippe G. Jorens c , Hugo Neels a , Adrian Covaci a,b a Toxicological Centre, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium b Laboratory for Ecophysiology, Biochemistry and Toxicology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium c Department of Clinical Pharmacology/Clinical Toxicology, University of Antwerp, Antwerp University Hospital, Universiteitsplein 1, 2610 Antwerp, Belgium article info Article history: Received 15 July 2010 Received in revised form 18 October 2010 Accepted 26 October 2010 Available online xxx Keywords: Pharmaceuticals Metabolites Influent wastewater Reversed-phase liquid chromatography–tandem mass spectrometry Solid-phase extraction Validation abstract A fast and sensitive high performance reversed-phase liquid chromatography–tandem mass spectrom- etry method was developed and validated for the analysis of 15 prescription pharmaceuticals and four of their metabolites in influent wastewater. The selected pharmaceuticals belonged to various classes, such as angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, calcium antagonists, -blockers, antidepressants, analgetics, anticonvulsants, platelet antiaggregants, and cholesterol lower- ing agents. They were selected from the list of top-sold prescription pharmaceuticals in Belgium. The chromatographic separation was optimized in order to achieve suitable retention times, good resolu- tion for analytes susceptible of mass spectrometric cross-talk and high sensitivity in one single run. All compounds eluted within 9 min on a Phenomenex Kinetex C18 column, based on a newly developed technology that allows a very narrow distribution of the core–shell particles, providing high separation efficiency. Sample preparation was executed with solid-phase extraction on Oasis MCX cartridges. The method was validated by assessing specificity, selectivity, lower limit of quantification (LLOQ), linearity, accuracy, precision, extraction recovery, and matrix effects following Food and Drug Administration guidelines. The method LLOQs ranged from 0.5 to 25 ng/L. Calibration curves and LLOQs were designed to provide a good analytical performance at concentrations expected in real influent wastewater samples for each target compound. Eight deuterated analogues were used as internal standards for quantifica- tion. The method was applied to influent wastewater samples collected from 17 different wastewater treatment plants throughout Belgium. Most of the analytes were measured in the samples at concen- trations above LLOQ. Seven of the compounds were for the first time reported in influent wastewater. The newly developed analytical method is currently used to assess relationships between sales figures of pharmaceuticals and their corresponding concentrations in influent wastewater. © 2010 Elsevier B.V. All rights reserved. 1. Introduction The widespread occurrence of pharmaceutical compounds in the environment is nowadays well established and as a result they are classified as emerging environmental contaminants [1]. The environmental impact of pharmaceuticals is believed to be primarily the consequence of their presence in the aquatic envi- ronment. Because of their immense worldwide consumption, ∗ Corresponding author at: Toxicological Centre, University of Antwerp, Univer- siteitsplein 1, 2610 Wilrijk-Antwerpen, Belgium. Tel.: +32 3 265 2743; fax: +32 3 265 2722. E-mail address: alexander.vannuijs@ua.ac.be (A.L.N. van Nuijs). pharmaceutically active compounds are continuously released in wastewater due to excretion via urine and/or faeces or due to direct disposal of leftovers. An incomplete removal of these phar- maceutical compounds in wastewater treatment plants (WWTPs) and drinking water treatment plants (DWTPs) is often observed, and as a result they can be detected in surface water and drinking water [2]. Because the acute and long-term effects of these com- pounds on the environment need to be studied more intensively, it is absolutely necessary that sensitive and specific analytical meth- ods are developed, validated and applied to monitor the presence of pharmaceuticals in wastewater, surface water and drinking water. Analytical methods to measure low concentrations (in the ng/L range or even lower) of pharmaceuticals in water samples of differ- ent sources should allow the simultaneous determination of a wide 0039-9140/$ – see front matter © 2010 Elsevier B.V. All rights reserved. doi:10.1016/j.talanta.2010.10.045