This is a M. Eng. degree project at Uppsala University carried out at Vattenfall NuclearFuel AB. The goal of it is to present a best estimate method based on the code package CASMO/SIMULATE for the purpose of calculating the isotopic concentrations of a specified number of isotopes in a fuel sample. The calculations done with the method shall produce small deviations from reliable measured values, which characterize the accuracy of CASMO/SIMULATE, but also simplicity based onthe computing time and handling of the amount of data is an important factor in the development of the method. The development of the method has been based on a sensitivity calculation with CASMO/SIMULATE on a number of relevant parameters affecting the isotope concentrations. The proposed method has then been applied on three samples irradiated in Ringhals 4 and Ringhals 3. At last the calculated isotopic concentrations have been benchmarked against measured data from Studsvik Laboratory. The sensitivity analyzes has shown that the parameters affecting the neutron moderation are very important for calculating the isotopic concentrations. The core axial resolution is also an important factor for the samples taken from top of the rod,where the power gradient is large. The comparison of the calculated and measured values has shown that SIMULATE, in the analysed cases, simulates a lower finalburnup. This has created a need to correct the final burnup in order to get better results in terms of lower relative deviations between the measured and calculated data.