We have used inductively coupled plasma mass spectrometry (ICP-MS) as the primary tool for determining concentrations of a suite of nuclides in samples excised from high-burnup spent nuclear fuel rods taken from light water nuclear reactors. The complete analysis included the determination of 95Mo, 99Tc, 101Ru, 103Rh, 109Ag, 137Cs, 143Nd, 145Nd,148Nd,147Sm, 149Sm, 150Sm, 151Sm, 152Sm, 151Eu, 153Eu, 155Eu, 155Gd, 237Np, 234U, 235U, 236U, 238U, 238Pu, 239Pu, 240Pu, 241Pu, 242Pu, 241Am, 242mAm, and 243Am. The isotopic composition of fissiogenic lanthanide elements was determined using high-performance liquid chromatography (HPLC) with ICP-MS detection. These analytical results allow the determination of fuel burn-up based on 148Nd, Pu, and U content, as well as provide input for storage and disposal criticality calculations. Results show that ICP-MS along with HPLC-ICP-MS are suitable of performing routine determinations of most of these nuclides, with an uncertainty of ±10% at the 95% confidence level.