In vitro metabolism of monensin A: microbial and human liver microsomes models

Bruno A. Rocha, Marilda D. Assis, Ana P. F. Peti, Luiz A. B. Moraes, Fernanda L. Moreira, Norberto P. Lopes, Paul J. Gates, Anderson R. M. de Oliveira*, Stanislav Pospíšil

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)

11 Citations (Scopus)

Abstract

1. Monensin A, an important antibiotic ionophore that is primarily employed to treat coccidiosis, selectively complexes and transports sodium cations across lipid membranes and displays a variety of biological properties.

2. In this study, we evaluated the fungi Cunninghamella echinulata var. elegans ATCC 8688A, Cunninghamella elegans NRRL 1393 ATCC 10028B and human hepatic microsomes as CYP-P450 models to investigate the in vitro metabolism of monensin A and compare the products with the metabolites produced in vivo.

3. Mass spectrometry analysis of the products from these model systems revealed the formation of three metabolites: 3-O-demethyl monensin A, 12-hydroxy monensin A and 12-hydroxy-3-O-demethyl monensin A. We identified these products by tandem mass spectrometry and through comparison with the in vivo metabolites.

4. This analysis demonstrated that the model systems produce the same metabolites found in in vivo studies, thus they could be used to predict the metabolism of monensin A. Furthermore, we verified that liquid chromatography coupled to mass spectrometry is a powerful tool to study the in vitro metabolism of drugs, because it allows the successful identifications of several derivatives from different metabolic models.

Original languageEnglish
Pages (from-to)326-335
Number of pages10
JournalXenobiotica
Volume44
Issue number4
DOIs
Publication statusPublished - Apr 2014

Keywords

  • Cytochrome P450
  • LC-ESI-MS/MS
  • mass spectrometry
  • microbial transformation
  • polyether ionophore
  • TANDEM MASS-SPECTROMETRY
  • STEREOSELECTIVE FUNGAL BIOTRANSFORMATION
  • STREPTOMYCES-CINNAMONENSIS
  • CAPILLARY-ELECTROPHORESIS
  • PHASE MICROEXTRACTION
  • ENDOPHYTIC FUNGUS
  • NATURAL-PRODUCTS
  • SODIUM MONENSIN
  • DRUG PROPERTIES
  • FRAGMENTATION

Cite this

Rocha, B. A., Assis, M. D., Peti, A. P. F., Moraes, L. A. B., Moreira, F. L., Lopes, N. P., Gates, P. J., de Oliveira, A. R. M., & Pospíšil, S. (2014). In vitro metabolism of monensin A: microbial and human liver microsomes models. Xenobiotica, 44(4), 326-335. https://doi.org/10.3109/00498254.2013.845707