A sensitive high-performance liquid chromatographic method using electrochemical detection for the analysis of olanzapine and desmethylolanzapine in plasma of schizophrenic patients using a new solid-phase extraction procedure

A high-performance liquid chromatographic method with amperometric detection for the analysis of the novel antipsychotic drug olanzapine and its metabolite desmethylolanzapine in human plasma has been developed. The analysis was carried out on a reversed-phase column (C8, 150×4.6 mm I.D., 5 μm) using acetonitrile–phosphate buffer, pH 3.8, as the mobile phase. The detection voltage was +800 mV and the cell and column temperature was 30°C. The flow-rate was 1.2 ml min−1. Linear responses were obtained between 5 and 150 ng ml−1, with repeatability <3.3%. A careful pretreatment of the biological samples was implemented by means of solid-phase extraction (SPE) on C8 cartridges. The method requires 500 μl of plasma for one complete analysis. Absolute recovery exceeded 97% for both olanzapine and desmethylolanzapine, and the detection limit was 1 ng ml−1 for both analytes. Repeatability, intermediate precision and accuracy were satisfactory. This sensitive and selective method has been successfully applied to therapeutic drug monitoring in schizophrenic patients treated with Zyprexa® tablets.