LC determination of oxcarbazepine and its active metabolite in human serum

Twenty-five percent of epileptic patients present refractory seizures to current frontline antiepileptic drugs, needing new treatments and leading to the introduction of several new AEDs, among which is oxcarbazepine (Trileptal). This 10-ketoanalogue of carbamazepine seems to be a weaker inducer of cytochrome P450 3A4. However, pharmacokinetic interactions with clinical significance have already been reported, before the marketing of Trileptal in France. The aim of this study was to develop and validate a HPLC method allowing simultaneous dosage of oxcarbazepine, 10-hydroxycarbamazepine, epoxycarbamazepine, carbamazepine, phenobarbital and phenyto?n. After plasma defecation by acetonitrile, dosage was obtained by analysis of the supernatants on a C(18) reversed-phase column coupled with UV detection (240 nm). The statistical validation was performed according to the recommendations of a European technical commission. This method seems to provide a quite good selectivity from the psychotropic therapeutics, which is commonly coprescribed with AEDs. Linearity was established for the whole concentration range, whatever the compound. Quantization limits of oxcarbazepine, 10-hydroxycarbamazepine, epoxycarbamazepine, carbamazepine, phenobarbital and phenyto?n are 0.58, 3.5, 2.35, 0.66, 1.02 and 3.13 microg/ml, respectively, and absolute recoveries are 105.15, 84.76, 94.45, 96.52, 98.62 and 95.08%, respectively.