In silico assessment of drug substances chemical stability

Evaluation of the influence of fluoroquinolone chemical structure on stability: forced degradation and in silico studies

“…Thus, in silico calculations are able to provide information about the behavior of molecules under specific circumstances, which may elucidate, theoretically, the stability of the quinolone class under certain conditions. These methodologies may be used to explain the degradation of quinolone chemical structures and also to identify some aspects which may influence their molecular reactivity (Kieffer et al, 2010;Kleinman et al, 2015).…”

Prediction of Drug Candidates' Sensitivity Toward Autoxidation: Computational Estimation of C-H Dissociation Energies of Carbon-Centered Radicals

“…Rule‐based methods like the ZENETH method have been developed to evaluate degradation risk and predict possible reaction pathways. Modeling of reaction pathways using first principal methods, for example, quantum mechanics (QM), has not been systematically investigated for pharmaceutical applications, although two short feasibility studies have been published …”

“…Modeling of reaction pathways using first principal methods, for example, quantum mechanics (QM), has not been systematically investigated for pharmaceutical applications, although two short feasibility studies have been published. 7,8 Here, we would like to present a systematic investigation on how well the quantum mechanical calculations can be used to predict the risk for autoxidation. The method outlined in this work is an extension to the previous work in which we presented a fully automated approach that has been optimized and simplified to allow a nonspecialist to perform the calculations and the following risk assessment.…”

4-[(4-acetylphenyl)amino]-2-methylidene-4-oxobutanoic acid, a newly synthesized amide with hydrophilic and hydrophobic segments: Spectroscopic characterization and investigation of its reactive properties

“…confirmation of the degradation path of some organic pharmaceutical molecules could be assessed by calculations of the BDE for hydrogen abstraction. [62][63][64][65][66][67][68][69][70][71][72][73][74][75] A molecule is considered suitable for an autoxidation mechanism when the BDE values are in the appropriate range. If the BDE values fall in the range between 75 to 85 kcal mol -1 , 76,77 the molecule could be considered as very sensitive to an autoxidation mechanism.…”