A calibration method for isotope dilution mass spectrometry is presented that fully accounts for non-linearity of calibration functions, caused by the interference of the analyte on the m/z used for measurement of the internal standard and vice versa. In this way, it is also possible to use incompletely labelled molecules or analogues with a mass increment of only 1 u for isotope dilution, on condition that certain restrictions are respected. In addition, the proposed method is less time consuming than bracketing. The method works with the computer-stored full Calibration curve and a single calibration point that is measured daily. The calibration curve is constructed from the experimentally determined mass spectral overlap between the unlabelled analyte and the labelled internal standard at the m/z values chosen for measurement. Measurement results for samples with unknown analyte concentration are calculated on the basis of a linear relationship between their ion abundance ratio and that of the daily single calibration point, but corrected by a factor derived from the theoretical calibration function. All calculations are performed with commonly available spreadsheet software, An application is presented for determining serum uric acid with a candidate gas chromatographic/ isotope dilution mass spectrometric reference method.