A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method coupled with column-switching technique was developed for the determination of olanzapine in rat brain microdialysates. A C8 guard column was used to desalt the samples before analytical separation on a C18 column and detection with tandem mass spectrometry. The mobile phase consisted of methanol/acetonitrile/water (v/v/v, 22.5/22.2/55) was used for desalting and the mobile phase consisted of methanol/acetonitrile/water (v/v/v, 43/43/14) was for analytical separation, water in both mobile phases contained 0.1% ammonium acetate. The lower limit of quantification (LLOQ) for olanzapine was 0.085 ng/ml. The method was linear from LLOQ to 34 ng/ml with a coefficient of determination >0.998. Intra- and inter-day accuracy and precision were determined with variability less than 13.24% (R.S.D). This sensitive method was successfully applied to quantify the concentration of olanzapine in rat brain microdialysates. With this study, the effect of the alcohol extract of Schisandra sphenanthera Rehd. et Wils on the concentration of olanzapine in brain was investigated.
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