A mechanism proposal for fluoxetine thermal decomposition

Thermal behavior of fluoxetine hydrochloride ((±)- N -methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine), an antidepressant of the selective serotonin reuptake inhibitor family, has been investigated using thermoanalytical techniques and evolved gas analysis performed with thermogravimetry coupled to Fourier transform infrared spectroscopy (TG-FTIR) and intermediate residue analysis by GC–MS. In inert atmosphere, the decomposition took place as two mass loss events with residue of 0.13% at the end of the run. In air atmosphere, decomposition occurred in three steps, the last one as a result of the oxidative burning of the carbonaceous matter. DTA and DSC curves demonstrated that sample melts at 159.6 °C (∆ H fus = 37.4 kJ mol −1 ) without recrystallization on cooling. Hot-stage microscopy data corroborate these observations. TG-FTIR studies revealed that fluoxetine decomposes after melting, releasing 4-trifluoromethylphenol, methylamine. GC–MS analysis of the solid resulting from heating the fluoxetine hydrochloride up to 230 °C revealed the presence of the original sample and 4-trifluoromethylphenol as the main residue. Based on these results, a mechanism for fluoxetine thermal decomposition was proposed.