title: Simultaneous and enantioselective liquid chromatographic determination of eslicarbazepine acetate, S-licarbazepine, R-licarbazepine and oxcarbazepine in mouse tissue samples using ultraviolet detection.
abstract: Herein is reported, for the first time, a simple and reliable chiral reversed-phase liquid chromatographic method coupled to ultraviolet (UV) detection for simultaneous determination of eslicarbazepine acetate (ESL) and its metabolites, S-licarbazepine (S-LC), R-licarbazepine (R-LC) and oxcarbazepine (OXC), in mouse plasma and brain, liver and kidney tissue homogenates. All analytes and the internal standard were extracted from plasma and tissue homogenates by a solid-phase extraction procedure using Waters Oasis hydrophilic-lipophilic balance cartridges. The chromatographic separation was performed by isocratic elution with water/methanol (88:12, v/v), pumped at a flow rate of 0.7 mL min(-1), on a LichroCART 250-4 ChiraDex (beta-cyclodextrin, 5 microm) column at 30 degrees C. The UV detector was set at 225 nm. Calibration curves were linear (r2 > or = 0.996) in the ranges 0.4-8 microg mL(-1), 0.1-1.5 microg mL(-1) and 0.1-2 microg mL(-1) for ESL and OXC and in the ranges 0.4-80 microg mL(-1), 0.1-15 microg mL(-1) and 0.1-20 microg mL(-1) for R-LC and S-LC in plasma, brain and liver/kidney homogenates, respectively. The overall precision not exceeded 11.6% (%CV) and the accuracy ranged from -3.79 to 3.84% (%bias), considering all analytes in all matrices. Hence, this method will be a useful tool to characterize the pharmacokinetic disposition of ESL in mice.
authors.affiliation: Laboratory of Pharmacology, Faculty of Pharmacy, Coimbra University, 3000-141 Coimbra, Portugal.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Alves
authors.forename: Isabel
authors.initials: I
authors.lastname: Figueiredo
authors.forename: Margarida
authors.initials: M
authors.lastname: Castel-Branco
authors.forename: Ana
authors.initials: A
authors.lastname: Loureiro
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
authors.forename: Margarida
authors.initials: M
authors.lastname: Caramona
mesh_terms: D000818:Animals; D002138:Calibration; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000032:analysis / Q000097:blood; D002853:Chromatography, Liquid / Q000379:methods* / Q000592:standards; D003984:Dibenzazepines / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D000078330:Oxcarbazepine; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D014018:Tissue Distribution
chemical_list: D003984:Dibenzazepines; D002220:Carbamazepine; C416835:eslicarbazepine acetate; D000078330:Oxcarbazepine; C428744:10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide