Forced degradation studies of norepinephrine and epinephrine from dental anesthetics: Development of stability‐indicating HPLC method and in silico toxicity evaluation

Injectable solutions containing epinephrine (EPI) and norepinephrine (NE) are not stable, and their degradation is favored mainly by the oxidation of catechol moiety. As studies of these drugs under forced degradation conditions are scarce, herein, we report the identification of their degradation p...

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Bibliographic Details
Published in:Biomedical chromatography 2020-07, Vol.34 (7), p.e4832-n/a
Main Authors: Coli Louvisse de Abreu, Letícia, Abrahim‐Vieira, Bárbara de Azevedo, Mendonça Teles de Souza, Alessandra, Pinto, Eduardo Costa, Gonçalves, Mariana da Silva, Simon, Alice, Viana, Gil Mendes, Rodrigues, Carlos Rangel, Pereira de Sousa, Valeria, Cabral, Lucio Mendes
Format: Article
Language:English
Subjects:
Anesthesia, Dental
Anesthetics - analysis
Anesthetics - chemistry
Anesthetics - toxicity
Animals
catecholamines, degradation products, risk assessment, stability‐indicating HPLC method
Chromatography, High Pressure Liquid - methods
Computer Simulation
Drug Stability
Epinephrine - analysis
Epinephrine - chemistry
Epinephrine - toxicity
Limit of Detection
Linear Models
Mice
Norepinephrine - analysis
Norepinephrine - chemistry
Norepinephrine - toxicity
Rats
Reproducibility of Results
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Summary:Injectable solutions containing epinephrine (EPI) and norepinephrine (NE) are not stable, and their degradation is favored mainly by the oxidation of catechol moiety. As studies of these drugs under forced degradation conditions are scarce, herein, we report the identification of their degradation products (DP) in anesthetic formulations by the development of stability‐indicating HPLC method. Finally, the risk assessment of the major degradation products was evaluated using in silico toxicity approach. HPLC method was developed to obtain a higher selectivity allowing adequate elution for both drugs and their DPs. The optimized conditions were developed using a C18 HPLC column, sodium 1‐octanesulfonate, and methanol (80:20, v/v) as mobile phase, with a flow rate of 1.5 mL/min, UV detection at 199 nm. The analysis of standard solutions with these modifications resulted in greater retention time for EPI and NE, which allow the separation of these drugs from their respective DPs. Then, five DPs were identified and analyzed by in silico studies. Most of the DPs showed important alerts as hepatotoxicity and mutagenicity. To the best of our acknowledgment, this is the first report of a stability‐indicating HPLC method that can be used with formulations containing catecholamines.
ISSN:0269-3879
1099-0801
DOI:10.1002/bmc.4832