Gas chromatographic/mass spectrometric assays for oxcarbazepine and its main metabolites, 10-hydroxy-carbazepine and carbazepine-10,11-trans-diol

Abstract

Oxcarbazepine (OCB) cannot be measured undecomposed by gas chromatography, not even when injected into a cooled, inert fused-silica capillary column. The bis-trimethylsilyl derivatives of the enol of OCB and of its main metabolite, 10-hydroxy-carbazepine (10-OH-CB), and the tris-trimethylsilyl derivative of carbazepine-10,11-trans-diol (CB-trans-diol) can be obtained easily at room temperature and are well suited for gas chromatographic and gas chromatographic/mass spectrometric analysis. Thermal decomposition to the substituted iminostilbene derivatives occurs only to the extent of a few per cent under the conditions described. Two gas chromatographic/mass spectrometric assays have been developed: one for the simultaneous quantification of OCB and 10-OH-CB, the other for CB-trans-diol. Both assays use carbazepine-10,11-cis-diol as the internal standard. Using 0.5 ml of plasma, limits of detection of 0.1, 0.1 and 1 ng/ml were obtained for OCB, 10-OH-CB and CB-trans-diol, respectively. CB-trans-diol is also the main metabolite of carbamazepine in patients under maintenance therapy. The kinetics of 15N-labelled CB-trans-diol derived from a single dose of (15N)carbamazepine has been measured in plasma and urine of patients and volunteers receiving (15N)carbamazepine in several studies.