A validated, accurate and sensitive LC-MS/MS method for determination of olanzapine and its metabolite N-desmethylolanzapine has been developed. The analytes were quantified by tandem mass spectrometry operating in positive electrospray ionization mode with multiple reaction monitoring. Olanzapine and desmethylolanzapine were extracted from serum or cerebral spinal fluid samples, 200 microl, with tert-butyl methyl ether using olanzapine-D3 as internal standard. Calibrations for olanzapine and desmethylolanzapine were linear within the selected range of 0.2-30 ng/ml (6-96 nM) in cerebral spinal fluid and for olanzapine in plasma, in the range of 5-100 ng/ml (16-320 nM). The method was successfully used for the analysis of samples from patients treated with olanzapine in the dose range of 2.5-25mg/day.
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