A multicolumn selectivity inversion generator separation method has been developed in which a desired daughter radionuclide is selectively extracted from a solution of the parent and daughter radionuclides by a primary separation column, stripped, and passed through a second guard column that retains any parent or other daughter impurities, while the desired daughter elutes. This separation method minimizes the effects of radiation damage to the separation material and permits the reliable production of radionuclides of high chemical and radionuclidic purity for use in diagnostic or therapeutic nuclear medicine.