Sample composition is a very important but easily ignored factor affecting the measurement of radionuclides in biological samples. In this paper, we study the effect of the chemical composition of the standard calibration source on determining radionuclides using Laboratory Sourceless Object Calibration Software. Results show that the accuracy of determining radionuclides emitting low-energy photons (<100 keV) strongly depends on the differences between the average atomic numbers of the test samples and selected standard reference material (SRM). We also find that high moisture content reduces detection efficiency, especially for low-energy gamma rays.