Low-level analysis of radioiodine performed by TIMS requires an initial chemical separation from interfering higher electron-affinity halogens. Experiments using I-125 and Cl-36 tracers have shown that iodide can be selectively oxidized and purged from solution while the chloride remains in the solution. A systematic investigation of the experimental factors that affect the oxidation and transfer of iodine along with the separation of iodide from chloride has been completed. Experimental design was used to determine the optimum experimental conditions by obtaining a better understanding of factor affects and interactions. Factors such as gas purge rate, experiment run time, and oxidant concentration were simultaneously studied in a central composite design of experiments and response surfaces were generated from results. Optimizing experimental factors resulted in improved iodide oxidation and transfer efficiencies, halogen separation, and shorter analysis times.