Thermal decomposition mechanism of tenofovir disoproxil fumarate

Tenofovir disoproxil fumarate (TDF) is an antiretroviral medication widely used to prevent and treat HIV/AIDS and to treat chronic hepatitis B. In this paper, thermal decomposition processes of TDF were measured with thermogravimetry, differential scanning calorimetry and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy. The IR spectra, high-performance liquid chromatography and liquid chromatography mass spectrometry of TDF and the residues of its thermal decomposition at various temperatures were determined. The molecular bond orders were calculated using an ab initio method from the GAMESS program of quantum chemistry. The mechanism of thermal decomposition was discussed. The results indicated that the thermal decomposition of TDF is a three-step process, the initial step of thermal decomposition of TDF is the decomposition of carboxylic ester, the first stage mainly is the decomposition of the phosphoric disoproxil section, and the second stage mainly is the decomposition of the tenofovir section and partially goes through adenine stage. The initial decomposition temperature in either nitrogen or air is 138 °C, and the thermal stability of TDF is not very good under routine temperature.