Enantioselective HPLC-UV method for determination of eslicarbazepine acetate (BIA 2-093) and its metabolites in human plasma.
Eslicarbazepine acetate (BIA 2-093) is a novel central nervous system drug undergoing clinical phase III trials for epilepsy and phase II trials for bipolar disorder. A simple and reliable chiral reversed-phase HPLC-UV method was developed and validated for the simultaneous determination of eslicarbazepine acetate, oxcarbazepine, S-licarbazepine and R-licarbazepine in human plasma. The analytes and internal standard were extracted from plasma by a solid-phase extraction using Waters Oasis HLB cartridges. Chromatographic separation was achieved by isocratic elution with water-methanol (88:12, v/v), at a flow rate of 0.7 mL/min, on a LichroCART 250-4 ChiraDex (beta-cyclodextrin, 5 microm) column at 30 degrees C. All compounds were detected at 225 nm. Calibration curves were linear over the range 0.4-8 microg/mL for eslicarbazepine acetate and oxcarbazepine, and 0.4-80 microg/mL for each licarbazepine enantiomer. The overall intra- and interday precision and accuracy did not exceed 15%. Mean relative recoveries varied from 94.00 to 102.23% and the limit of quantification of the assay was 0.4 microg/mL for all compounds. This method seems to be a useful tool for clinical research and therapeutic drug monitoring of eslicarbazepine acetate and its metabolites S-licarbazepine, R-licarbazepine and oxcarbazepine.
Alves
Gilberto
G
Laboratory of Pharmacology, Faculty of Pharmacy, Coimbra University, Coimbra, Portugal.
Figueiredo
Isabel
I
Castel-Branco
Margarida
M
Loureiro
Ana
A
Fortuna
Ana
A
Falcão
Amílcar
A
Caramona
Margarida
M
D002138:Calibration / Q000592:standards; D002220:Carbamazepine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D003984:Dibenzazepines / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods; D004355:Drug Stability; D006801:Humans; D015394:Molecular Structure; D000078330:Oxcarbazepine; D010949:Plasma / Q000737:chemistry; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
D003984:Dibenzazepines; D002220:Carbamazepine; C416835:eslicarbazepine acetate; D000078330:Oxcarbazepine