Quantification of fumarate and investigation of endogenous and exogenous fumarate stability in rat plasma by LC-MS/MS.
Bioanalysis
; 8(7): 661-75, 2016 Apr.
Article
em En
| MEDLINE
| ID: mdl-26978279
ABSTRACT
BACKGROUND:
Fumaric acid is a commonly used excipient in pharmaceutical products. It is not known if its presence may lead to fluctuation of endogenous fumarate levels. An LC-MS/MS method was developed and validated to quantify fumarate in support of a toxicokinetics study.RESULTS:
Stability evaluation showed that endogenous fumarate was stable for 6 h at room temperature, while exogenously added fumaric acid was converted to malate within 1 h due to the presence of fumarase. Citric acid, a fumarase inhibitor, prevented the conversion of added fumaric acid in rat plasma.CONCLUSION:
The method was validated in citric acid stabilized rat plasma using a surrogate matrix approach. A discrepancy in stability was observed between endogenous fumarate and exogenously added fumaric acid.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cromatografia Líquida de Alta Pressão
/
Espectrometria de Massas em Tandem
/
Fumaratos
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article