Thermal degradation of clozapine-N-oxide to clozapine during gas chromatographic analysis.

Studies were undertaken to determine if clozapine-N-oxide, the principal urinary metabolite of the antipsychotic agent clozapine, may interfere with the gas chromatographic-mass spectrometric bioanalysis of clozapine. Following injection of clozapine-N-oxide onto a (5% phenyl)methylpolysiloxane capillary column operated at 250 degrees C, significant on-column reduction of clozapine-N-oxide to the parent drug occurred. Accordingly, preparation of biological samples for clozapine determination by gas chromatography should avoid conditions which reportedly co-extract the N-oxide to assure no artifactual contribution of this metabolite in the detection of clozapine.