Molecular Structural Studies of Captopril Drug, Using Thermal Analysis, Mass Spectral Fragmentation and Semi-Empirical MO- Calculations

In this work captopril an antihypertensive (KPL) drug, was investigated using thermal analysis (TA) measurements (TG-DTA) in comparison with electron impact (EI) mass spectral (MS) fragmentation at 70 eV. Semi-empirical molecular (MO) calculations, using PM3 method in the neutral and positively charged forms of the drug. These include molecular geometry, bond order, charge distribution, heats of formation and ionization energy. The behavior of the drug under drug TA decomposition, reveal a moderate stability up to 160Co before a completely decomposition in the range 160-240 Co. The initial decomposition is due to COOH + CH3 loss, followed by SH loss. On the other hand, the molecular ion can easily fragmented by CO2 loss followed by SH loss. This is the best-selected pathway comparable with decomposition using TA. MO-Calculation is used to declare these observations. Key word: Captopril; thermal analysis; electron impact; MO calculation. Several methods are in use for captopril analysis. These include spectrophotometry2, chromatography3, electro 4, AAS5 . Ford and timmins6 , pointed out use of thermal analysis in the characterization of pharmaceutical solids and the use of thermal analysis in the development of solid dosage forms. The decomposition rate of KPL was studied using isothermal and rising temperature methods on a simultaneous thermal analysis TG-DTA unit7. The thermal behavior of KPL and its cabalt complex was studied8. Mass spectrometry is an 1696 ARAFA, Orient. J. Chem., Vol. 30(4), 1695-1701 (2014) indispensable tool in chemistry, biochemistry , pharmacy, and medicine9 . The technique is important for drug metabolism studies because it provides a large amount of structural information with little expenditure of sample10 . In electron impact (EI) mass spectrometry , the fragmentation consist of a series of competitive, and consecutive unimolecular fragmentation11 . Thermo gravimetric ( TG / DTG ) analysis is used to provide quantitative information on weight losses due to decomposition and evaporation of low molecular material as a function of time or temperature . In conjunction between mass spectral fragmentation , and thermal decomposition process, the nature of the interpretation of thermal degradation can provide additional data, which can be used successfully for interpretation of experimental results of fragmentation processes12. Although the literature is wealthy in information related to the biological activities of KPL, and its derivatives , it seems a lack of any correlation between chemical behavior, and its electronic structure of this drug. In the present work, we have investigated the behavior of KPL, upon electron impact mass spectrometry at 70 eV, and thermal analysis (TA) measurement (TG-DTA, and DSC). Also MO calculation are performed using PM3 procedure on the neutral molecular and charged species to investigate bond order, atomic charge distribution, and heat of formation . These calculation are correlated with that obtained from both TA and ms to know information about the stability of the drug, and prediction of the site primary fragmentation step, and subsequent ones