Development and validation of a high performance liquid chromatographic method for the determination of oxcarbazepine and its main metabolites in human plasma and cerebrospinal fluid and its application to pharmacokinetic study.
An isocratic reversed-phase HPLC-UV procedure for the determination of oxcarbazepine and its main metabolites 10-hydroxy-10,11-dihydrocarbamazepine and 10,11-dihydroxy-trans-10,11-dihydrocarbamazepine in human plasma and cerebrospinal fluid has been developed and validated. After addition of bromazepam as internal standard, the analytes were isolated from plasma and cerebrospinal fluid by liquid-liquid extraction. Separation was achieved on a X-TERRA C18 column using a mobile phase composed of 20 mM KH(2)PO(4), acetonitrile, and n-octylamine (76:24:0.05, v/v/v) at 40 degrees C and detected at 237 nm. The described assay was validated in terms of linearity, accuracy, precision, recovery and lower limit of quantification according to the FDA validation guidelines. Calibration curves were linear with a coefficient of variation (r) greater than 0.998. Accuracy ranged from 92.3% to 106.0% and precision was between 2.3% and 8.2%. The method has been applied to plasma and cerebrospinal fluid samples obtained from patients treated with oxcarbazepine, both in monotherapy and adjunctive therapy.
Kimiskidis
Vasilios
V
3rd Department of Neurology, George Papanicolaou Hospital, Aristotle University of Thessaloniki, Greece.
Spanakis
Marios
M
Niopas
Ioannis
I
Kazis
Dimitrios
D
Gabrieli
Chrysi
C
Kanaze
Feras Imad
FI
Divanoglou
Daniil
D
D000097:Acetonitriles / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D000927:Anticonvulsants / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000493:pharmacokinetics; D001711:Biotransformation; D002021:Buffers; D002138:Calibration; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000097:blood / Q000134:cerebrospinal fluid / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D016903:Drug Monitoring / Q000379:methods; D004827:Epilepsy / Q000097:blood / Q000134:cerebrospinal fluid; D017408:Guidelines as Topic; D006801:Humans; D016014:Linear Models; D000078330:Oxcarbazepine; D010710:Phosphates; D017680:Potassium Compounds; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet / Q000379:methods
D000097:Acetonitriles; D000588:Amines; D000927:Anticonvulsants; D002021:Buffers; D010710:Phosphates; D017680:Potassium Compounds; D012997:Solvents; D002220:Carbamazepine; C004822:10,11-dihydro-10,11-dihydroxy-5H-dibenzazepine-5-carboxamide; C013216:potassium phosphate; C008699:octylamine; D000078330:Oxcarbazepine; C032159:acetonitrile