title: A chiral liquid chromatography method for the simultaneous determination of oxcarbazepine, eslicarbazepine, R-licarbazepine and other new chemical derivatives BIA 2-024, BIA 2-059 and BIA 2-265, in mouse plasma and brain.
abstract: Recently, in silico models have been developed to predict drug pharmacokinetics. However, before application, they must be validated and, for that, information about structurally similar reference compounds is required. A chiral liquid chromatography method with ultraviolet detection (LC-UV) was developed and validated for the simultaneous quantification of BIA 2-024, BIA 2-059, BIA 2-265, oxcarbazepine, eslicarbazepine (S-licarbazepine) and R-licarbazepine in mouse plasma and brain. Compounds were extracted by a selective solid-phase extraction procedure and their chromatographic separation was achieved on a LiChroCART 250-4 ChiraDex column using a mobile phase of water-methanol (92:8, v/v) pumped at 0.7 mL/min. The UV detector was set at 235 nm. Calibration curves were linear (r(2)  ≥ 0.996) over the concentration ranges of 0.2-30 µg/mL for oxcarbazepine, eslicarbazepine and R-licarbazepine; 0.2-60 µg/mL for the remaining compounds in plasma; and 0.06-15 µg/mL for all the analytes in brain homogenate. Taking into account all analytes at these concentration ranges in both matrices, the overall precision did not exceed 9.09%, and the accuracy was within ±14.3%. This LC-UV method is suitable for carrying out pharmacokinetic studies with these compounds in mouse in order to obtain a better picture of their metabolic pathways and biodistribution.
authors.affiliation: Pharmacology Department, Faculty of Pharmacy, University of Coimbra, 3000-548, Coimbra, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Fortuna
authors.forename: Gilberto
authors.initials: G
authors.lastname: Alves
authors.forename: Anabela
authors.initials: A
authors.lastname: Almeida
authors.forename: Bruno
authors.initials: B
authors.lastname: Lopes
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002138:Calibration; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D003984:Dibenzazepines / Q000097:blood / Q000378:metabolism*; D051379:Mice; D000078330:Oxcarbazepine; D011786:Quality Control; D012015:Reference Standards; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D000927:Anticonvulsants; D003984:Dibenzazepines; D002220:Carbamazepine; C571001:eslicarbazepine; D000078330:Oxcarbazepine; C428744:10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide