Methods for the determination of drug residues in water have been developed based on the combination of liquid chromatography (LC) or capillary electrophoresis (CE) with mass spectrometry (MS). For HPLC-MS two types of interfaces (pneumatically assisted electrospray ionization interface or an atmospheric pressure chemical ionization interface, respectively) were employed and compared in terms of detection limits. 2 mM Ammonium acetate at pH 5.5 and a methanol gradient was used for the HPLC-MS allowing the separation of a number of drugs such as paracetamol, clofibric acid, penicillin V, naproxen, bezafibrate, carbamazepine, diclofenac, ibuprofen and mefenamic acid. A 20 mM ammonium acetate solution, pH 5.1 was employed for the separation of clofibric acid, naproxen, bezafibrate, diclofenac, ibuprofen and mefenamic acid by CE-MS. Sample pretreatment was performed by solid-phase extraction (SPE) for HPLC-MS or by a combination of liquid-liquid extraction and SPE for CE-MS. The applicability of both the HPLC-MS and CE-MS method was demonstrated for several river water samples. (C) 2001 Elsevier Science B.V. All rights reserved.