Investigation of naproxen drug using mass spectrometry, thermal analyses and semi-empirical molecular orbital calculation

Naproxen (C14H14O3) is a non-steroidal anti-inflammatory drug (NSAID). It is important to investigate its structure to know the active groups and weak bonds responsible for medical activity. In the present study, naproxen was investigated by mass spectrometry (MS), thermal analysis (TA) measurements (TG/DTG and DTA) and confirmed by semi empirical molecular orbital (MO) calculation, using PM3 procedure. These calculations included, bond length, bond order, bond strain, partial charge distribution, ionization energy and heat of formation (ΔHf). The mass spectra and thermal analysis fragmentation pathways were proposed and compared to select the most suitable scheme representing the correct fragmentation pathway of the drug in both techniques. The PM3 procedure reveals that the primary cleavage site of the charged molecule is the rupture of the COOH group (lowest bond order and high strain) which followed by CH3 loss of the methoxy group. Thermal analysis of the neutral drug reveals a high response to the temperature variation with very fast rate. It decomposed in several sequential steps in the temperature range 80-400 °C. These mass losses appear as two endothermic and one exothermic peaks which required energy values of 255.42, 10.67 and 371.49 J g−1 respectively. The initial thermal ruptures are similar to that obtained by mass spectral fragmentation (COOH rupture). It was followed by the loss of the methyl group and finally by ethylene loss. Therefore, comparison between MS and TA helps in selection of the proper pathway representing its fragmentation. This comparison is successfully confirmed by MO-calculation.