A new method is presented for the determination of 12 acidic pharmaceuticals (non-steroidal anti-inflammatory drugs and bezafibrate), including two metabolites from aqueous samples, together with triclosan as a personal care product. Ion-pair liquid chromatography (IP-LC) with electrospray ionisation tandem mass spectrometry (ESI-MS) in the negative ion mode was employed. The ion-pairing agent (tri-n-butylamine) increased the signal intensity for all acidic analytes and detection limits of 6–200 ng/L were obtained by multiple reaction monitoring. This allows analysis of wastewater samples by direct injection into the LC/MS system without the need for a preceding enrichment step. When combined with a solid-phase extraction (SPE) step, limits of quantification between 0.15 and 11 ng/L were obtained from 100-mL sample volumes, which is adequate for most applications. The occurrence of matrix effects was studied and standard addition was required for reliable quantification after SPE from wastewater. The method was finally applied to surface and wastewaters, with analyte concentrations ranging from below the detection limit up to 5.5 μg/L. Copyright © 2004 John Wiley & Sons, Ltd.