Quantitative determination of olanzapine in rat brain tissue by high-performance liquid chromatography with electrochemical detection |
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| Institution: | 1. Faculty of Life Sciences and Medicine, Institute of Pharmaceutical Science, King''s College London, UK;2. Centre for Ultrastructural Imaging, King''s College London, Guy''s Campus, London, UK;3. Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK;4. Department of Infectious Diseases, Centre for Clinical Infection and Diagnostics Research (CIDR), King''s College London & Guy''s and St. Thomas'' NHS Foundation Trust (GSTT), London, UK |
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| Abstract: | A sensitive assay was developed for the measurement of olanzapine in rat brain tissue using HPLC with electrochemical detection. The assay has a lower limit of quantitation of 0.5 ng/ml in tissue homogenate and utilizes a liquid–liquid extraction followed by reversed-phase HPLC for the quantitative analysis of olanzapine. The method provided a linear response for olanzapine over a concentration range of 0.5–100 ng/ml with a coefficient of determination (r2) greater than 0.9995. The extraction efficiencies of olanzapine and internal standard (LY170158) were greater than 82% in brain tissue. The intra-assay and inter-assay relative errors ranged from −5.38 to 17.60% and −3.25 to 10.53%, respectively. The intra-assay and inter-assay RSD values were in the range of 1.12 to 6.96% and 3.78 to 6.68%. Long-term stability studies showed that brain tissue homogenate samples spiked with olanzapine and internal standard are stable at −70°C for at least 110 days. However, a room temperature stability study showed that olanazapine was not stable in brain homogenate if the sample was exposed at 25°C longer than 2 h. This method has been used for the study of the disposition and pharmacokinetics of olanzapine in male Sprague–Dawley rats. |
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