In this study, the use of co-occurring discriminators of sewage and manure was assessed as a potential way to disentangle sewage and manure sources. A suite of human and veterinary derived chemical markers, which includes pharmaceuticals and compound such as food additives, has been identified for this purpose. The suite was selected in such a manner as to provide additional source characterisation, e.g. differentiating raw versus treated sewage inputs. An SPE-LC-MS/MS method was developed and validated for the determined suite of chemical markers with a detection limit of up to 50 pg . This represents one of the lowest limits of detection for pharmaceuticals reported in literature. To illustrate the suitability of the proposed method to differentiate sewage and manure inputs to surface water bodies, results from surface water samples collected at monitoring sites corresponding to specific land use types within Ireland are discussed.