In 2015, an estimated 11,134.97 tonnes of antibiotics were consumed by humans in 59 countries. This figure is projected to increase to 128 billion doses by 2030. Antibiotics that are not fully metabolised by the organism end up in wastewater treatment plants. Conventional wastewater treatment plants cannot completely remove antibiotics, which remain in anaerobic treated effluents (ATEs). ATEs themselves lead to the occurrence of antibiotic resistance genes due to their interaction with microbes in treatment facilities. This establishes a clear link between antibiotic use and antibiotic resistance, which causes over 700,000 deaths per year. Thus, it is necessary to accurately measure antibiotic levels in the environment, but the precision of existing methods is limited by the occurrence of matrix effects. Matrix effects are an increase (ion enhancement) or decrease (ion suppression) in the response of the target analyte. Due to this, matrix effects can dramatically alter the performance of an analytical method. The aim of this work was to determine and measure the presence and concentration of antibiotics in water using Solid Phase Liquid Extraction (SPE) and Liquid Chromatography-Mass Spectrometry (LC-MS). SPE was performed using Oasis HLB 200 µg cartridges, and the retained analyte was eluted with acetonitrile and reconstituted in a 10:10:80 methanol:acetonitrile:water solution. LC-MS/MS analysis was completed using an Agilent HPLC instrument with a 1290 Infinity II LC multi-sampler and temperature-regulated sample tray and column compartment. The columns used were a Zorbax eclipse plus C18 2.1 x 50 mm 1.8 μm LC column and a Zorbax eclipse plus C18, 2.1 x 5 mm, 1.8 μm UHPLC guard column at 30 ̊C. A 6470A triple-quadrupole mass spectrometer with electrospray ionisation (Agilent Technologies) was used for detection. Helium was used as a collision gas and N2 as a nebulising and desolvation gas. Data was collected using MassHunter software. The antibiotic sulfamethoxazole (SMX) was detected in each of the investigated surface water bodies in Ireland. The highest detected concentration was 3.2 ng/L showing a matrix effect of 321% (6.33% matrix effect SD). At present, there is no method developed for the detection of antibiotics that is not subjected to inaccuracies due to matrix effects. The developed optimised method allows for the precise and accurate detection of antibiotics in water samples, by decreasing the occurrence of matrix effects to improve sensitivity.