Abstract The use of active pharmaceutical ingredients (APIs) is increasing continuously and thereby constitutes a potential source of surface water contamination. Environmental concentrations of APIs are usually at trace levels, generally in low ng/L concentrations, making them challenging to detect. However, these low concentrations can be sufficient to induce toxic effects on the aquatic environment. This project focuses on selected APIs, which are probably the most common in the aquatic environment. Several of the compounds selected are on The Norwegian Institute of Public Health’s (NIPH’s) list over the most prescribed APIs in Norway throughout 2014. A rapid, sensitive and selective method was developed and validated for screening of seven APIs (acetaminophen, atenolol, fluoxetine, sulfapyridine, sulfamethoxazole, trimethoprim and xylazine) in surface water. The method include an on-line automatic filter and filter back flush (AFFL) solid phase extraction (SPE) in combination with capillary liquid chromatography (capLC) coupled to a triple quadrupole mass analyser (MS). By combining large volume injection (100 μL) and the AFFL-SPE-system, a rugged and high throughput switching system was obtained. The analytes were loaded under non-eluting condition and further trapped on a reversed phase (RP) Kromasil (C18, 5 mm x 1 mm ID, 5 μm) SPE-column with a flow rate of 150 μL/min. A 10 minutes gradient was applied using an ACE C18 column (150 mm x 0.3 mm ID, 3 μm) as analytical column with a flow rate of 4 μL/min. The mobile phases (MP) for loading and MP A consisted of type 1 water with 0.1 % formic acid (FA) and the organic MP (MP B) consisted of 100 % methanol with 0.1 % FA (pH 2.7). The total analysis time was 15 minutes including 6 minutes reconditioning. This study demonstrates that the AFFL-SPE-capLC system combined with a triple quadrupole MS enables the detection of selected classes of APIs in surface water in a concentration range of 10-100 ng/L. The calculated concentration limit of detection (cLOD) for the selected APIs was in the 2– 18 ng/L range and calculated concentration limit of quantification (cLOQ) in the 5 – 54 ng/L range. Acceptable linearity (R2 = 0.9777-0.9998) and generally high apparent recovery values (from 69-288 %) with generally relative standard deviation (RSD %) lower than 20 % were found.