title: Development and validation of an HPLC-UV method for the simultaneous quantification of carbamazepine, oxcarbazepine, eslicarbazepine acetate and their main metabolites in human plasma.
abstract: For the first time, a simple, selective and accurate high-performance liquid chromatography method with ultraviolet detection was developed and validated to quantify simultaneously three structurally related antiepileptic drugs; carbamazepine, oxcarbazepine, and the recently launched eslicarbazepine acetate and their main metabolites, carbamazepine-10,11-epoxide, 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine, and licarbazepine. The method involves a solid-phase extraction and a reverse-phase C18 column with 5 cm length. The mobile phase consisting of water, methanol, and acetonitrile in the ratio 64:30:6 was selected as the best one and pumped at 1 mL/min at 40 degrees C. The use of this recent column and an aqueous mobile phase instead of buffers gives several advantages over the method herein developed; namely the fact that the chromatographic analysis takes only 9 min. The method was validated according to the guidelines of the Food and Drug Administration, showing to be accurate (bias within +/-12%), precise (coefficient variation <9%), selective and linear (r(2) > 0.997) over the concentration range of 0.05-30 microg/mL for carbamazepine; 0.05-20 microg/mL for oxcarbazepine; 0.15-4 microg/mL for eslicarbazepine acetate; 0.1-30 microg/mL for carbamazepine-10,11-epoxide; 0.1-10 microg/mL for 10,11-trans-dihydroxy-10,11-dihydro-carbamazepine, and 0.1-60 microg/mL for licarbazepine. It was also shown that this method can adequately be used for the therapeutic drug monitoring of the considered antiepileptic drugs, carbamazepine, oxcarbazepine, eslicarazepine acetate, and their metabolites.
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: Joana
authors.initials: J
authors.lastname: Sousa
authors.forename: Gilberto
authors.initials: G
authors.lastname: Alves
authors.forename: Amílcar
authors.initials: A
authors.lastname: Falcão
authors.forename: Patrício
authors.initials: P
authors.lastname: Soares-da-Silva
mesh_terms: D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003984:Dibenzazepines / Q000097:blood*; D006801:Humans; D015394:Molecular Structure; D000078330:Oxcarbazepine; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D003984:Dibenzazepines; D002220:Carbamazepine; C416835:eslicarbazepine acetate; C012227:carbamazepine epoxide; D000078330:Oxcarbazepine; C428744:10,11-dihydro-10-hydroxy-5H-dibenz(b,f)azepine-5-carboxamide