Analytical Method Development for the Simultaneous Determination of Five Human Pharmaceuticals in Water and Wastewater Samples by Gas Chromatography-Mass Spectrometry O. A. H. Jones / N. Voulvoulis*/ J. N. Lester Environmental Processes and Water Technology Unit, Department of Environmental Science and Technology, Imperial College, London, SW7 2BP, UK; E-Mail: n.voulvoulis@imperial.ac.uk Key Words Gas chromatography-mass spectrometry Solid phase extraction Pharmaceuticals Water and wastewater analysis Summary Effective analytical methods for the simultaneous determination of five pharmaceuticals from various therapeutic classes in a variety of aqueous samples have been developed and method performance data are presented. The method involves the simultaneous extraction of the se- lected pharmaceuticals from the aqueous phase by solid phase extraction using a hyper cross linked, polystyrene-divinylbenzene polymer based sorbent. Analytes were eluted with metha- nol, derivatised with N-methyl-N-trimethylsilyltrifloroacetamide and analysed by gas chroma- tography – electron ionisation mass spectrometry (GC-EI-MS). Recoveries of 50 to 98% were established for waters spiked with the studied compounds at the low ng L )1 level with the highest detection sensitivities being achieved in the selected ion monitoring (SIM) mode and the quantification limit of the procedure for sample sizes of 1000 ml was approximately 5 ng L )1 for all matrices except sewage which was only tested to 20 ng L )1 . Analysis of domestic sewage from a large treatment works demonstrate the presence of all five compounds in both influents and effluents. Introduction Reports of the occurrence of a wide variety of both human and veterinary medicines in the aquatic environment have been increasing steadily in recent years [1]. Despite their likely continuous discharge, little is known about the ulti- mate fate and transport of many drug substances after their intended applica- tion. This has lead to pharmaceuticals, attracting increasing attention as water pollutants due to their possible environ- mental effects [2]. While the production of pharmaceu- tical compounds is a potential route for drugs to the environment [3], human pharmaceuticals are thought to be more likely to come from point sources such as sewage treatment works (STW) [4]. This is because human excreta may contain incompletely metabolised medicines (up to 90% of an administered dose [5]) of medication, in addition unused medicines are frequently disposed of via the sewage system. Drugs have been shown to pass intact through conventional sewage treatment works, into waterways, lakes and aquifers [6–8] and discarded phar- maceuticals may end up at landfill sites, posing a threat to underlying groundwa- ter [9, 10]. Quantitative evaluation of the fate and behaviour of pharmaceutical compounds in the aquatic environment requires sen- sitive and reliable analytical methods with detection limits in the lower ng L )1 range [11]. In the past, the analytical determi- nation of pharmaceuticals has been mainly limited to biological samples such as blood, tissue and urine [12]. A simple adaptation of these methods to environ- mental studies is not generally appropri- ate because the therapeutic dose of pharmaceuticals is usually much higher than the levels found in the environment and elevated levels of potentially inter- fering compounds such as humic sub- stances often have to be separated out. This has meant that until relatively recently, few analytical methods to detect these compounds in environmental sam- ples at relevant concentrations had been developed [13]. Analytical procedures for the deter- mination of pharmaceuticals in aqueous samples utilise both gas and liquid chro- matography after extraction and clean up procedures [10, 14–16]. A detailed review of analytical methods has recently been undertaken [17]. However environmental studies frequently require data on the distribution of contaminants within DOI: 10.1365/s10337-003-0087-6 2003, 58, 471–477 0009-5893/03/10 $03.00/0 Ó 2003 Friedr. Vieweg & Sohn Verlagsgesellschaft mbH Original Chromatographia 2003, 58, October (No. 7/8) 471