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Forced degradation studies of norepinephrine and epinephrine from dental anesthetics: Development of stability‐indicating HPLC method and in silico toxicity evaluation
Author(s) -
Coli Louvisse de Abreu Letícia,
AbrahimVieira 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
Publication year - 2020
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.4832
Subject(s) - chemistry , forced degradation , high performance liquid chromatography , chromatography , degradation (telecommunications) , in silico , methanol , catechol , methylparaben , reversed phase chromatography , preservative , biochemistry , organic chemistry , telecommunications , computer science , gene
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.