Occurrence and Behavior of X-ray Contrast Media in Sewage Facilities and the Aquatic Environment THOMAS A. TERNES* AND ROMAN HIRSCH ESWE-Institute for Water Research and Water Technology, So ¨hnleinstrasse 158, D-65201 Wiesbaden, Germ any The occurrence of iodinated X-ray contrast media derived from radiological examinations was investigated in German municipal sewage, sewage treatment plant (STP) effluents, rivers, and groundwater using LC-electrospray tandem MS detection. The four X-ray contrast media, diatrizoate, iopamidol, iopromide, and iomeprol are ubiquitously distributed in the sewage and in the aquatic environment. The X-ray contrast media were not significantly eliminated during the sewage treatment processes close to Frankfurt/Main. On weekdays the loading of the X-ray contrast media was significantly increased, because X-ray examinations are performed in hospitals and radiological practices predominately from Monday to Friday. The maximum concentration measured in STP effluents was 15 µg/L for iopamidol. Due to the high contamination of STP effluents with X-ray contrast media, the respective receiving waters (rivers and creeks) were also highly polluted. Median values up to 0.49 µg/L for iopamidol and 0.23 µg/L for diatrizoate were determined. In groundwater these polar compounds were present up to concentrations as high as 2.4 µg/L for iopamidol. Since X-ray contrast media are predominantly applied in human medicine, the polluted municipal STP effluents are presumably the sole sources for the contamination of the aquatic environment. Introduction Many different pharmaceuticals and corresponding me- tabolites have been recently identified in the aquatic environment. First results of drug residues in STP effluents and the environment were mainly focused on clofibric acid, the active metabolite of three lipid regulators. In the United States,Garrison et al.(1)and Hignite and Azarnoff(2)detected clofibric acid in the lower µg/L-range in treated wastewater. Furtherinvestigationsare reported from the United Kingdom, where pharmaceuticals were present in the aquatic environ- ment at concentrations up to approximately 1 µg/ L (3-5). In Germany, clofibric acid has been identified in river and groundwater and even in drinkingwater with concentrations ranging up to 165 ng/L by Stan and Linkerha ¨ger (6) and Heberer and Stan (7). Our institute identified a range oflipid regulators,antiinflammatoryagents,analgesics,betablockers, 2-sympathomimetics, antiepileptic drugs (i.e. carbam- azepine), antibiotics, and several metabolites in sewage treatment plant (STP) effluents and river water (8-12). However,environmentaldata foriodinated X-raycontrast media are still missing, although those compounds are currently applied in Germany in high annual amounts. In Germanyin totalapproximately500t/a ofallapproved X-ray contrast media are applied, whereas iopromide alone ac- countsfor130t/a(13).Iodinated X-raycontrast media exhibit a high biochemical stability and, hence, are excreted mainly nonmetabolized (14, 15). Moreau et al. (14) outlined that radiographic diagnostics represent the major proportion of all pharmaceuticals used in hospitals. Gartiser et al. (17) showed that X-ray contrast media are the main contributors to the burden oftotal adsorbable organic halogens (AOX) in clinical wastewater. The behavior and even the occurrence ofiodinated X-ray contrast media in rivers, groundwater, and drinking water is mostly unknown. Wischnack et al. (18) used adsorbable organic iodine (AOI) detection and showed that organic compounds containing iodine atoms are present in the aquatic environment and in drinking water up to 7 µg/ L. They assumed that AOI contamination was due primarily to the presence of iodinated X-ray contrast media. However, this has not yet been confirmed by individual component identification. Most ofthose radiographic contrast media are derivatives of2,4,6-triiodobenzoic acid possessing polar carboxylic and hydroxy moieties in their side chains (Tables 1 and 2). The iodinated X-ray contrast media can roughly be divided into the ionic agents containing a free carboxylic moiety and the nonionic agents in which all carboxylic moieties are amide derivatives. Due to their relatively high molecular weight (600-800 u) and their high polarity, methods allowing detection limits in the ng/L-range (presumed environmental concentrations) were not described. The methods reported in the literature focused mainly on biological samples such as blood serum and urine.Recently,we developed a method enabling the analysis of individual X-ray media in aqueous environmental samples down to lower ng/L-range (19). The objective of this paper was to determine the con- tamination ofsewage,STPeffluents,rivers,and groundwater with individual X-ray-contrast media, in order to compare their environmental concentrations with other pharmaceu- ticals already reported in the literature. Experimental Section Analytical Method. For the determination ofiodinated X-ray contrast media in aqueous matrices a sensitive method was developed using solid-phase extraction (Isolute ENV + mate- rial) and detection by liquid chromatography-electrospray tandem mass spectrometer (LC-electrospray tandem MS) (19). The sample (1 L) was glass fiber filtered (<1 µm) and spiked with the surrogate standard Desmethoxy Iopromide (DMI) and the pH was adjusted with H2SO4 (c ) 3 m o l/ L) to 2.8. Then, the sample was sucked with approximately 10 mL/min through a glass cartridge filled with Isolute ENV+/ IST material. The cartridges were dried for 1 h with nitrogen and eluted four times with 1 mL of methanol. The extracts were reduced to approximately 20 µL in a gentle nitrogen stream and made up to 200 µLwith ammonium acetate buffer (10 mmol/L ammonium acetate). Fifty microliters of the extract was injected onto the HPLC column. A125 × 3mm LiChrospher/MerckRP-18column,5 µm (alternatively a 150 × 2.1 mm Intertsil phenyl-3/GL Sciences Inc., 3 µm ), was used at room temperature with an isocratic flow of 0.4 mL/ min of a water/acetonitrile eluent (92/8 v/v) containing 10 mmol/Lofammonium acetate. The detection was achieved usingmultiple reaction monitoring(MRM)ofLC-electrospray tandem MS (API III plus and API 365; both from Perkin- Elmer) in the positive ion mode, allowing a sensitive *Corresponding author phone: ++6117804343; fax: 0611- 7804375; e-mail: Thomas.ternes@stadtwerke-wiesbaden.de. Environ. Sci. Technol. 2000, 34, 2741-2748 10.1021/es991118m CCC: $19.00  2000 American Chemical Society VOL. 34, NO. 13, 2000 / ENVIRONMENTAL SCIENCE & TECHNOLOGY 9 2741 Published on Web 06/06/2000