title: Liquid chromatography-tandem mass spectrometric assays for salinomycin in mouse plasma, liver, brain and small intestinal contents and in OptiMEM cell culture medium.
abstract: Fast and sensitive liquid chromatography-tandem mass spectrometric assays for the determination of salinomycin in mouse plasma, liver, brain and small intestinal contents and in OptiMEM cell culture medium, were developed and validated using simple sample pre-treatment procedures. Tissue samples were homogenized with phosphate buffered saline or, for high levels in liver, with human plasma. After addition of monensin as the internal standard to plasma, homogenate or culture medium and acetonitrile extraction for tissue and plasma, the diluted medium or the supernatant was directly injected into the isocratic chromatographic system using a polar embedded reversed-phase column and formic acid in water-acetonitrile as the eluent. The eluate was completely led into an electrospray interface with positive ionization and the analytes were quantified using triple quadrupole mass spectrometry. The assays were successfully validated in the ranges 10-2000 ng/ml for OptiMEM cell culture medium, 1-2000 ng/ml for plasma and 3-2000 ng/g in liver brain and small intestinal contents. At the lowest levels, the intra-day precisions were < or =9%, inter-day precisions were < or =14% and accuracies were between 91 and 112%. The analytes were chemically stable under all relevant conditions and the assays were applied in different in vitro transport studies and in pharmacokinetic and tissue distribution studies with salinomycin in mice.
authors.affiliation: Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Sorbonnelaan 16, Utrecht, The Netherlands. r.w.sparidans@pharm.uu.nl
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Sparidans
authors.forename: Jurjen S
authors.initials: JS
authors.lastname: Lagas
authors.forename: Afred H
authors.initials: AH
authors.lastname: Schinkel
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D003470:Culture Media; D007421:Intestine, Small / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011714:Pyrans / Q000097:blood / Q000302:isolation & purification / Q000378:metabolism*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000095662:Polyether Polyketides
chemical_list: D000900:Anti-Bacterial Agents; D003470:Culture Media; D011714:Pyrans; C010327:salinomycin; D000095662:Polyether Polyketides