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

Abstract

A simple, sensitive and robust liquid chromatography/electrospray ionization tandem mass spectrometry (LCESI-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 x 2.1 mm i.d., 5 microm) 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 5.2%. This validated method has been successfully used to quantify the rat plasma and brain tissue concentration of ziprasidone after chronic treatment.

Quantitative determination of icotinib in human plasma and urine using liquid chromatography coupled to tandem mass spectrometry

“…HPLC-MS/MS method has been extensively used to investigate pharmacokinetic profiles of new drugs owing to its high specificity, sensitivity and rapid analysis speed. This is especially for selected ion monitoring (SIM) and multiple reaction monitoring (MRM) scan mode [3][4][5][6][7][8]. Up to now, there has only been one reported determination method for icotinib in plasma of beagle dogs [9].…”

Determination of aripiprazole in rat plasma and brain using ultra‐performance liquid chromatography/electrospray ionization tandem mass spectrometry

“…Matrix effects can have significant influence on the sensitivity of compounds in LC‐MS/MS. Our laboratory has reported many HPLC‐MS/MS methods to analyze different antipsychotics simultaneously in rat plasma and brain tissue (Zhang et al ., ,,,, ). In these methods, liquid–liquid extraction was used successfully and there were no serious matrix effects.…”

Development and validation of stability indicating UPLC assay method for ziprasidone active pharma ingredient

“…[1,2] Ziprasidone is most effective in schizophrenia, a chronic illness that requires lifelong treatment spread over approximately 1% of the world's population. [3,4] Literature survey for ziprasidone revealed several analytical methods based on different techniques, viz, LC-MS [5][6][7] assay for their quantification in plasma and brain, high performance liquid chromatography (HPLC) [8][9][10] method for simultaneous determination of ziprasidone in capsule formulation, and HPLC-UV [11] methods for determination ziprasidone in human plasma and urine, LC [12] with fluorescence for determination of plasma ziprasidone, and capillary zone electrophoresis [13] for determination of ziprasidone in pharmaceutical formulations.…”