Thermal desorption gas chromatograph mass spectrometry (TD GC/MS) was used to study weight loss in thermogravimetric analysis (TGA). The technique of thermal desorption utilizes the same temperature heating rate as the TGA to thermally desorb volatiles from solid sample matrices. Volatiles were cryo-trapped at -60 degrees C. After thermal desorption is complete, the trapped volatiles are separated by a GC capillary column and identified by mass spectrometry. In this study, the TD GUMS was applied in pharmaceutical development to understand the chemical reactions attributed to the weight loss in the thermal decomposition of two dicarboxylic acid salts of a drug substance. These two salts exhibited different thermal stabilities. The thermally induced chemical reactions obtained from these two salts included dehydration and decarboxylation. Thermal degradation compounds were identified and reaction pathways for decomposition were proposed. The stability of the salts is dependent on the identity of the dicarboxylic acids from which they were generated. The information obtained from TD GUMS helps better understand the weight loss process in thermogravimetric analysis. (C) 2005 Elsevier B.V. All rights reserved.