title: In vitro metabolism of monensin A: microbial and human liver microsomes models.
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.
authors.affiliation: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo (FFCLRP-USP) , Ribeirão Preto , Brazil .
authors.forename: Bruno A
authors.initials: BA
authors.lastname: Rocha
authors.forename: Marilda D
authors.initials: MD
authors.lastname: Assis
authors.forename: Ana P F
authors.initials: AP
authors.lastname: Peti
authors.forename: Luiz A B
authors.initials: LA
authors.lastname: Moraes
authors.forename: Fernanda L
authors.initials: FL
authors.lastname: Moreira
authors.forename: Norberto P
authors.initials: NP
authors.lastname: Lopes
authors.forename: Stanislav
authors.initials: S
authors.lastname: Pospíšil
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Gates
authors.forename: Anderson R M
authors.initials: AR
authors.lastname: de Oliveira
mesh_terms: D002853:Chromatography, Liquid; D020093:Cunninghamella / Q000737:chemistry; D006801:Humans; D007476:Ionophores / Q000378:metabolism; D008099:Liver / Q000187:drug effects*; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000187:drug effects*; D008985:Monensin / Q000378:metabolism*; D009181:Mycoses / Q000188:drug therapy* / Q000382:microbiology; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D007476:Ionophores; D008985:Monensin