Gas chromatographic assay for oxcarbazepine and its main metabolites in plasma

Abstract

The new anti-epileptic drug oxcarbazepine is temperature-labile and decomposes under the conditions of gas chromatography, even when injected into a cooled, inert, fused-silica capillary column. In contrast, the trimethylsilyl derivative of oxcarbazepine is stable. The bis-trimethylsilyl derivatives of the enol of oxcarbazepine and of its active metabolite, 10-hydroxycarbazepine, and the tris-trimethylsilyl derivative of carbazepine-10,11-trans-diol can be synthesized easily at room temperature. Using the readily available carbamazepine as internal standard, a simple gas chromatographic assay was developed for the simultaneous routine measurement of these three compounds at therapeutic levels. This assay is ten times more sensitive to oxcarbazepine than the previously described high-performance liquid chromatographic assays. It involves a single-step solvent extraction, uses a fused-silica capillary column and a flame ionization detector. On processing 0.5 ml of plasma, limits of detection of 10 ng/ml were obtained for oxcarbazepine and 10-hydroxycarbazepine and a limit of detection of 25 ng/ml for carbazepine-10,11-trans-diol.