This study introduces the general method of differential scanning calorimetry (DSC) for the purity assessment of chemical reference substances (CRSs). Thirty high-purity chemical reference substances were calibrated by the DSC method and the uncertainty of the measurements was calculated. The DSC method provided comparable CRS purity and uncertainty results to the method based on principle of mass balance (mass balance method). Therefore, the DSC method can be used for the purity assessment of suitable CRS. Purity determination by DSC has the advantage of practicality, speed, reproducibility, no corresponding reference standard requirement and no sample preparation is required. The DSC method is complementary to the mass balance method for the assay of chemical reference substances. (C) 2011 Elsevier B.V. All rights reserved.