neurotoxicity and mechanisms of induced hyperexcitability

1 -The primary site fragmentation process and its majorfragmentation pathways in both techniques.2 -The stability of the drug as a neutral molecule in thesolid-state phase and molecular ion in the gas phase.3 -Selection of the most probable decomposition pathwayin both TA and MS.Thermal analysis (TA)The TG/DTA curves of DMP (Fig. 2) were displayed between25ºC and 600ºC. The drug has the general formulaC 18H 25NO.HBr.H 2O in solid-state phase with a molecularweight (MW) of 370.3 and melting point (m.p.) 125 ºC.It is clear from the thermal survey of the drug that thereare four mass losses in the TGA (Table 1). The first oneappeared at 100-150ºC with a mass loss % of 4.1, whichmay be attributed to the loss of water present in the drug(cal. mass loss % = 4.8). The second mass loss was approximately32.5% and occurred at 150-350ºC. The third onewas 54.57% and occurred at 350-450ºC. The final one was5.68% and occurred at 450-600ºC, which may be attributedto the loss of the remainder. These mass losses were observedat the three main peaks at values: 120.8ºC, 287.2ºCand 378.6ºC in DTG, respectively. These mass losses alsoappeared as two endothermic peaks in the DTA. The firstone appeared at 110.77ºC, requiring an energy E 1= +242.6J/g, and the second one appeared at 362ºC, requiring anenergy E 2= + 356.75 J/g. The fragmentation of this compoundand its chemical changes occurring after this thermaldegradation appeared at 555.56ºC as a very strong exothermicpeak requiring an energy E 3= 513.5 J/g.Fig.2a : TGA curve of Dextromethorphan HydrobromideFig.2b : Dr.TGA of Dextromethorphan HydrobromideMass spectral behaviour of dextromethorphan (MS)The electron impact (EI) mass spectrum for DMP drugat 70 eV was recorded and investigated. A typical massspectrum (barograph) of the drug is shown in Fig. 3.Scheme 1 shows the proposed principal fragmentationpathways of DMP following electron impact at 70 eV. Inaddition, prominent ions and their relative intensities withsome common ions formed from codeine [26] are listedFig 2 C: DTA of Dextromethorphan HydrobromideTable 1: Structure identification of Dextromethorphan HydrobromideTGADTAWt. loss% Temp.range o C Peak temp. o C Descripion E J/g4.10 100-150 118.77 Endothermic +242.632.50 150-350 367.6 endothermic +365.7554.57 350-450 555.56 St.exothermic peak -613.55.68450-600ΣWt.loss %=96.85*Dr. TGA gives three main peaks temperatures at 120.58, 287.23 and 378.62 oC.23