Investigation of diazepam drug using thermal analyses, mass spectrometry and semi-empirical MO calculation

In the present work diazepam (Dz) drug was investigated using thermal analyses (TA) measurements (TG/DTG) in comparison with EI mass spectral (MS) fragmentation at 70 and 20 eV. Semi-empirical MO calculations, MNDO procedure, have been carried out on diazepam both as neutral molecule and the corresponding positively charged molecular ion. These include molecular geometry, bond order, charge distribution, heats of formation and ionization energy. Thermogravimetric and kinetic analysis, reveal a high response of the drug to the temperature variation with very fast rate. It is completely decomposed in the temperature range between 204 and 340 degrees C with average kinetic energy (KE) at 164.69 kJ mol(-1). On the other hand, diazepam can easily fragmented at low energy after ionization by electron energy at 9.56 eV. The losses of CO gas molecules followed by chlorine gas from the entity of diazepam (both neutral and charged molecular ion) as the best selected pathway were observed in both mass spectra (MS) and thermal analyses (TA). MNDO calculation was applied to declare both TA and MS observations.     

Study of some phenolic-iodine redox polymeric products by thermal analyses and mass spectrometry

Summary This paper describes the use of the mass spectrometry (MS), thermal analyses (TA) and other physico-chemical methods to investigate the structure of two newly synthesized phenolic-iodine derivative polymeric products. These two products are formed as a result of redox-interaction of adrenaline hydrogen tartrate (AHT, I) with iodate (IO^-₃) and periodate (IO^-₄). The characterization of the two products were achieved satisfactorily by using the above tools and their proposed general formulae, were found to be C₅₂H₆₇O₃₆N₄I (AHT- IO^-₃, II) and C₂₆H₃₄O₁₈N₂I₂(AHT- IO^-₄, III). The fragmentation behavior of the main compound (AHT) in MS and TA (TG and DTA) techniques was investigated and compared. The results obtained were used to explain the fragmentation of the products AHT- IO^-₃and AHT- IO^-₄in mass spectrometry and thermal analyses techniques. The stabilities of different fragments were discussed. The results indicate that the two techniques are supporting each other in which the mass spectrometry provides the structural information in gas phase while the thermal analyses provides the quantitative fragmentation in the solid-state.     

Structure characterization and spectroscopic investigation of ciprofloxacin drug

Ciprofloxacin (CPF, C₁₇H₁₈FN₃O₃) drug is used in the treatment of some bacterial infectious diseases. The drug was investigated using thermal analysis (TA) measurements (TG/DTG) and electron impact mass spectral (EI-MS) fragmentation at 70 eV techniques. Furthermore, the drug was characterized and investigated by other spectroscopic tools as IR, UV–Vis, ¹H-, and ¹³C-NMR. Semi-empirical MO calculation using PM3 procedure has been carried out on neutral molecule and positively charged species. The calculations included, bond length, bond order, bond strain, partial charge distribution, ionization energy, and heat of formation (ΔH _f). The PM3 procedure provides a basis for fine distinction among sites of initial bond cleavage, which is crucial to the rationalization of subsequent fragmentation of the molecule. The mass spectra and thermal analysis fragmentation pathways were proposed and compared to each other to select the most suitable scheme representing the correct fragmentation of this drug. From EI-MS, the main primary cleavage site of the charged molecule is that due to C–COOH bond cleavage with H-rearrangement to skeleton and CO₂ loss which can further decompose by piperazine loss. Thermal analysis of the neutral form of the drug reveals the high response of the drug to the temperature variation with very fast rate. Thermal decomposition has carried out in several sequential steps in the temperature range 40–650 °C. The initial thermal decomposition is similar to that obtained by mass spectrometric fragmentation (C–COOH fragment) but differ in that a rearrangement occurs by OH and CO loss. Therefore, comparison between MS and TA helps in selection the proper pathway representing the fragmentation of this drug. This comparison successfully confirmed by MO calculation. Finally, the effect of fluorine atom on the stability of the drug was discussed.     

Mass spectra of gliclazide drug at various ion sources temperature

Gliclazide (GL, C₁₅H₂₁N₃O₃S) drug is used as non-insulin-dependant diabetes mellitus. The drug was investigated using thermal analysis (TA) measurements (TG/DTG) and electron impact mass spectral (EI–MS) fragmentation at 70 eV techniques. The mass spectra of GL at different values of ion source temperatures (400, 416, 425, and 440 K) are recorded and investigated. Semiempirical MO calculation, 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, ionization energy, and heats of formation (ΔH _f). PM3 procedure provides a basis for fine distinction among sites of initial bond cleavage, which is crucial to the rationalization of subsequent fragmentation of the molecule. The primary fragmentation pathway in both TA and MS (at different values of ion source temperature) is initiated by S–N bond rupture. TA and DTG show one main weight loss at 250.38 °C and four peaks at 271.6, 360.99, 427.93 and 479.17 °C in DTA, which may be attributed to various fragments. Also, the rate constant (K′) of thermal degradation has been tested isothermally at 210 and 600 °C. The calculated rate values are 9.6 × 10⁻³ and 0.33 × 10⁻³ s⁻¹, respectively, and discussed. In MS, the effect of ion source temperature on mass spectral fragmentation processes is discussed on the basis of energy considerations using quasi equilibrium theory.     

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

Sertraline (C(17)H(17)Cl(2)N) 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 70eV. 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 (DeltaH(f)). Also, in the present work sertraline-iodine product was prepared and its structure was investigated using elemental analyses, IR, (1)H NMR, (13)C 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 CH(3)NH(2)(+) 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 CH(2)NH(+) fragment ion loss. In thermal analyses (TA) the initial rupture in sertraline is due to the loss of C(6)H(3)Cl(2) followed by the loss of CH(3)-NH forming tetraline molecule which thermally decomposed to give C(4)H(8), C(6)H(6) or the loss of H(2) 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 CH(3)NH followed by the loss of C(6)H(5)HI 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.     

[C7H7]+ and [C6H5]+ fragment ions produced from methylphenol isomers by electron impact

Appearance energies for [C₇H₇]⁺ and [C₆H₅]⁺ fragment ions obtained from methylphenol isomers were measured at the threshold using the electron impact technique. Different processes for the formation of the ions are suggested and discussed. Metastable peaks were detected and the kinetic energies released were determined. The results indicate that [C₇H₇]⁺ ions are formed from metbylpbenois with both benzyl and tropylium structures, whereas [C₆H₅]⁺ ions are formed with the phenyl structure at the detected thresholds. Kinetic energies released on fragmentation of reactive [ C₇H₇]⁺ and [C₆H₅]⁺ ions were used as a probe for the structure of the ions at 70 eV.     

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

Ibuprofen (C₁₅H₁₈O₂) is an anti-inflammatory drug. It is important to investigate its structure to know the active groups and weak bond responsible for its medical activity. Consequently in the present study, ibuprofen was investigated by mass spectrometry (MS) and thermal analyses (TAs) (TG/DTG and DTA), and confirmed by semi-empirical molecular orbital (MO) calculation using PM3 procedure, on the neutral and positively charged forms of the drug. These calculations included bond order, bond length, and bond strain, and charge distribution, heat of formation, and ionization energy. The mass spectra and thermal analysis fragmentation pathways were proposed and compared to each other to select the most suitable scheme representing the correct fragmentation pathway of the drug in both techniques. From the electron ionization (EI) mass spectra, the primary cleavage site of the charged molecule is because of the rupture of COOH group (the lowest bond order) followed by propyl group loss. The TAs of the drug revealed high response of the drug to the temperature variation with very fast rate. It decomposed in several sequential steps in the temperature range 25–360 °C. The initial thermal decomposition is similar to that obtained by MS fragmentation of the first rupture (COOH), then subsequent one of propyl loss, and finally of ethylene loss. These mass losses appear as endothermic peaks required energy values of −214.83, −895.95, and −211.10 J g⁻¹, respectively. The order of these losses is also related to the values of the MO calculation parameters. Therefore, the comparison between MS and TA helps in the selection of the proper pathway representing the decomposition of this drug to give its metabolites in in vivo system. This comparison is also successfully confirmed by MO calculations.