Structure investigation of sertraline drug and its iodine product using mass spectrometry, thermal analyses and MO-calculations

Sertraline (C17H17Cl2N) as an antidepressant drug was investigated using thermal analysis (TA) measurements (TG/DTG and DTA) in comparison with electron impact (EI) mass spectral (MS) fragmentation at 70 eV. Semi-empirical MO-calculations, using PM3 procedure, has been carried out on neutral molecule and positively charged species. These calculations included bond length, bond order, bond strain, partial charge distribution and heats of formation (ΔHf). Also, in the present work sertraline-iodine product was prepared and its structure was investigated using elemental analyses, IR, 1H NMR, 13C NMR, MS and TA. It was also subjected to molecular orbital calculations (MOC) in order to confirm its fragmentation behavior by both MS and TA in comparison with the sertraline parent drug. In MS of sertraline the initial rupture occurred was CH3NH2+ fragment ion via H-rearrangement while in sertraline-iodine product the initial rupture was due to the loss of I+ and/or HI+ fragment ions followed by CH2NH+ fragment ion loss. In thermal analyses (TA) the initial rupture in sertraline is due to the loss of C6H3Cl2 followed by the loss of CH3–NH forming tetraline molecule which thermally decomposed to give C4H8, C6H6 or the loss of H2 forming naphthalene molecule which thermally sublimated. In sertraline-iodine product as a daughter the initial thermal rupture is due to successive loss of HI and CH3NH followed by the loss of C6H5HI and HCl. Sertraline biological activity increases with the introduction of iodine into its skeleton. The activities of the drug and its daughter are mainly depend upon their fragmentation to give their metabolites in vivo systems, which are very similar to the identified fragments in both MS and TA. The importance of the present work is also due to the decision of the possible mechanism of fragmentation of the drug and its daughter and its confirmation by MOC.