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

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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.

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