Determination of the lipophilic antipsychotic drug ziprasidone in rat plasma and brain tissue using liquid chromatography-tandem mass spectrometry

A simple, sensitive and robust liquid chromatography/electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method with low matrix effects was developed and validated for the quantification of the lipophilic antipsychotic ziprasidone from rat plasma and brain tissue. Ziprasidone was extracted from rat plasma and brain homogenate using a single-step liquid-liquid extraction. Ziprasidone was separated on an Agilent Eclipse XDB C₈ column (150 × 2.1 mm i.d., 5 μm) column using a mobile phase of acetonitrile-0.02% ammonia in water (pH 7.20 adjusted with formic acid) using gradient elution. Ziprasidone was detected in the positive ion mode using multiple reaction monitoring. The method was validated and the specificity, linearity, lower limit of quantitation (LLOQ), precision, accuracy, recovery, matrix effects and stability were determined. The LLOQ was 0.2 ng/mL for plasma and 0.833 ng/g for brain tissue. The method was linear over the concentration range from 0.2 to 200.0 ng/mL for plasma and 0.833-833.3 ng/g for brain tissue. The correlation coefficient (R²) values were more than 0.996 for both plasma and brain homogenate. The precision and accuracy intra-day and inter-day were better than 8.13%. The relative and absolute recovery was above 81.0% and matrix effects were lower than 52%. This validated method has been successfully used to quantify the rat plasma and brain tissue concentration of ziprasidone after chronic treatment.