Methods in this group measure total impurity levels in absolute terms.
Differential scanning calorimetry. This technique is used to check the presence of different polymorphic forms and to determine the total amount of solid impurities. Purity estimation is based on determination of the heat of fusion of the sample and of the change in its melting point caused by the presence of impurities. This analytical method can be performed rapidly and with high precision. However, it is not applicable if the substance decomposes on melting. This limits its value as a general procedure for purity estimation of chemical reference substances. It is also inapplicable if solid solutions are formed.
Phase solubility analysis. The method has occasionally been used, but its value is limited and the procedure is time consuming. It may be employed to detect contaminating substances, including isomeric species, and to estimate their concentration. Some factors that may make the method inapplicable are degradation of the substance during the course of analysis, formation of a solid solution, and polymorphism in the main component.