Daniela Secci, Marcello Locatelli*, Abuzar Kabir, Erika Salvatorelli, Giorgia Macedonio, Adriano Mollica and Simone Carradori* Pages 313 - 320 ( 8 )
Background: New Chemical Entities (NCEs) could be generally exposed to several stress conditions of hydrolysis, oxidation, photolysis and thermal degradation in order to better characterize the compounds and to know if the degradation processes lead to generate undesired (or toxic) products.
Objective: This paper reports the development and validation of an HPLC-PDA method for the qualiquantitative profiles determination and chemical-physical stability evaluation after forced decomposition studies of thiosemicarbazone-derived compounds endowed with interesting pharmacological activities.
Methods: All compounds and two possible degradation products were resolved by using a Grace® C-18 (ODS) column (250 mm × 4.6 mm; 5 mm particle size) in gradient elution mode. The chromatographic analysis was run in 28 min. The analytical method was correctly validated using weighted-matrix matched standard curves in the following ranges: 1-100 µg mL-1 for the lead compounds, and 0.1-8 μg mL-1 for the two possible degradation products showing a good correlation coefficients (≥0.9756). Precision and trueness comply with International Guidelines on method validation.
Results: The obtained results demonstrated an excellent stability of the thiosemicarbazone-derived products following the treatment with UV set at 254 nm and heat (at 80°C). In solution, however, the compounds showed different stability profiles.
Conclusion: The results obtained through the forced degradation studies provided important information not only for handling, formulation and storage of the substances, but also for the possible chemical changes in order to increase the stability. Given the importance of the non-conventional dosage forms, the stability of the substances was also analyzed in the presence of widely used surfactants.
Forced decomposition studies, HPLC-PDA, method validation, new chemical entities, stability tests, thiosemicarbazone derivatives.
Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University of Rome, p.le A. Moro 5, 00185 Rome, Department of Pharmacy, , International Forensic Research Institute, Department of Chemistry and Biochemistry, Florida International University, Miami, FL, Department of Pharmacy, , Department of Pharmacy, , Department of Pharmacy, , Department of Pharmacy