title: Use of microbore LC-MS/MS for the quantification of oxcarbazepine and its active metabolite in rat brain microdialysis samples.
abstract: A microbore LC-MS/MS method is developed and validated for the quantification of the anti-epileptic drug oxcarbazepine (OXC) and its active metabolite 10,11-dihydro-10-hydroxycarbamazepine (MHD) in rat brain microdialysates, together with the internal standard for microdialysis probe calibration, 2-methyl-5H-dibenz(b,f)azepine-5-carboxamide (m-CBZ). The benefits of gradient versus isocratic separation are shown, next to the improved sensitivity resulting from the addition of 0.1% formic acid to the mobile phase. The coupling of microdialysis with ESI-MS requires sample desalting for which column switching was applied. Using weighed regression to calculate the calibration curves (1-1000 ng/mL), the assay was validated in terms of linearity, accuracy and precision, yielding a sensitive (limit of quantification is 1 ng/mL) and selective method for quantification of OXC, MHD and m-CBZ. By applying this method, we were able to determine the extracellular concentrations of OXC and MHD during at least 4h after intraperitoneal (i.p.) administration of 10 mg/kg OXC.
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Lanckmans
authors.forename: Ralph
authors.initials: R
authors.lastname: Clinckers
authors.forename: Ann
authors.initials: A
authors.lastname: Van Eeckhaut
authors.forename: Sophie
authors.initials: S
authors.lastname: Sarre
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Yvette
authors.initials: Y
authors.lastname: Michotte
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D002853:Chromatography, Liquid / Q000295:instrumentation / Q000379:methods*; D006624:Hippocampus / Q000737:chemistry; D008297:Male; D013058:Mass Spectrometry; D017551:Microdialysis; D000078330:Oxcarbazepine; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results
chemical_list: C039775:10,11-dihydro-10-hydroxycarbamazepine; D002220:Carbamazepine; D000078330:Oxcarbazepine