title: 1H NMR monitoring of the canine metabolic profile after oral administration of xenobiotics using multivariate statistics.
abstract: This study describes a chemometric analysis of 1H NMR spectra of canine plasma following oral single dose administrations of two food components (lycopene and oleuropein) and of two drug products, Fungoral (ketoconazole) and Adalat (nifedipine). Due to the high interday physiological variation, 1H NMR plasma data were first filtered (by applying orthogonal signal correction) and then subjected to principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA). A distinct discrimination was achieved between samples obtained with and without administration of xenobiotics using both techniques. According to distance to model criterion and as shown by the Cooman's plots there was no overlap between the four models which proved to be specific for each xenobiotic. Moreover, it was shown that this approach has the potential to recognize subtle variations in the metabolic profile even if the administered xenobiotic itself could not be detected in the canine plasma by conventional HPLC methods.
authors.affiliation: Department of Pharmaceutical Chemistry and Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, National & Kapodistrian University of Athens, Panepistimiopolis, Zografou, Athens, Greece.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Constantinou
authors.forename: Maria
authors.initials: M
authors.lastname: Vertzoni
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
authors.forename: Anna
authors.initials: A
authors.lastname: Tsantili-Kakoulidou
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Mikros
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002338:Carotenoids / Q000097:blood; D003198:Computer Simulation; D004285:Dogs; D005260:Female; D005544:Forecasting; D057888:Iridoid Glucosides; D039823:Iridoids; D000077276:Lycopene; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008660:Metabolism; D015999:Multivariate Analysis; D009543:Nifedipine / Q000097:blood; D010949:Plasma / Q000378:metabolism*; D011522:Protons; D011714:Pyrans / Q000097:blood; D015262:Xenobiotics / Q000494:pharmacology*
chemical_list: D057888:Iridoid Glucosides; D039823:Iridoids; D011522:Protons; D011714:Pyrans; D015262:Xenobiotics; C002769:oleuropein; D002338:Carotenoids; D009543:Nifedipine; D000077276:Lycopene