A simple, yet robust analytical method was developed to detect and quantify three sulfonamides (SA), namely sulfamethoxazole (SMO), sulfachloropyridazine (SCP), and sulfamethazine (SM), and a macrolide tylosin (TT) in aqueous (calcium chloride and leachate solutions) and solid (agricultural soils) matrices using high performance liquid chromatography and ultra violet detection at 290 nm (TT) and 275 nm (SA) respectively. Chromatography was performed using a Phenomenex Onyx Monolithic C(18) column for TT and a C(18) Luna column for sulfonamides as single analytes eluted isocratically with a mobile phase consisting of acetonitrile: trifluoroacetic acid: tetrahydrofuran in the ratio 22.5:68:9.5 for TT, 40:55:5 for SMO, 32:63:5 for SCP and 31:64:5 for SM (v/v) at 1.0 mL min(-1) and an injection volume of 20 μL. A gradient method to detect all three sulfonamides in a single run was also developed. The soil residue analysis consisted of extraction with dichloromethane and pre-concentration steps as the aqueous phase was measured directly. The limits of detection at an S/N (signal: noise) ratio of 3 were 20.0 μg L(-1) and 50 μg L(-1) for all sulfonamides and tylosin respectively. The average recoveries for all sulfonamides and tylosin in aqueous matrices ranged from 95 to 105% across the six concentrations investigated. Recoveries from the soils were slightly lower for sulfonamides and tylosin. The isocratic method was used to determine the sorption and degradation of sulfonamides in soils, while the gradient method was used to determine degradation kinetics and leachate concentrations in soils and aqueous systems.