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Compound-specific stable-isotope analysis (CSIA) has greatly facilitated assessment of sources and transformation processes of organic pollutants. Multielement isotope analysis is one of the most promising applications of CSIA because it even enables distinction of different transformation pathways. This review introduces the essential features of continuous-flow isotope-ratio mass spectrometry (IRMS) and highlights current challenges in environmental analysis as exemplified for the isotopes of nitrogen, hydrogen, chlorine, and oxygen. Strategies and recent advances to enable isotopic measurements of polar contaminants, for example pesticides or pharmaceuticals, are discussed with special emphasis on possible solutions for analysis of low concentrations of contaminants in environmental matrices. Finally, we discuss different levels of calibration and referencing and point out the urgent need for …