Thermal and degradation study of candesartan under pyrolysis and oxidizing conditions

Author(s)

Ferreira, Laura Teofilo ; Mannochio-Russo, Helena ; Isquibola, Guilherme ; Fernandes, Richard Perosa ; de Mourac, Aniele ; Bolzani, Vanderlan da Silva ; Caires, Flavio Junior

• Document type: Journal article
• Source: JOURNAL OF ANALYTICAL AND APPLIED PYROLYSIS; v. 173, p. 9-pg., 2023-06-17.

Abstract

Candesartan is a widely used active pharmaceutical ingredient in the treatment of systemic arterial hypertension. This work presents the investigation of the thermal behavior of candesartan, such as its thermal stability, melting temperature, and thermal decomposition, both in pyrolysis (N2) or oxidizing (air) conditions by evolved gas analysis (EGA). The thermal study showed that the drug melts at 189 degrees C (onset at 184 degrees C) followed by decomposition in six mass loss steps. The drug presents a similar thermal behavior under pyrolytic and oxidizing conditions up to 360 degrees C. The main gaseous products released are N2O, NH3, CO, CO2, HCN, and CH3CH2NCO (ethyl isocyanate). Pyrolysis degradation products have been analyzed, and a thermal degradation pathway has been proposed with fifteen different structures based on the HRMS and MS/MS analysis. Furthermore, the characterization of the pyrolytic degradation products of candesartan by UHPLC-HRMS is reported for the first time, showing that the initial degradation pathway occurs through a dimerization reaction. (AU)

• FAPESP's process: 18/24378-6 - Synthesis, characterization and thermoanalytical study of Valsartan, Candesartan Cilexetil and Olmesartan medoxomil co-crystals
• Grantee: Flávio Junior Caires
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
• Grantee: Glaucius Oliva
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/50926-0 - INCT 2014: biodiversity and natural products
• Grantee: Vanderlan da Silva Bolzani
• Support Opportunities: BIOTA-FAPESP Program - Thematic Grants