Development of a simple and specific uhplc assay for the determination of aripiprazole and dehydroaripiprazole in rat plasma


Uʇur D. Y., Işil T., YILMAZ A., ŞENER E.

Journal of the Chilean Chemical Society, vol.60, no.3, pp.3049-3053, 2015 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 60 Issue: 3
  • Publication Date: 2015
  • Journal Name: Journal of the Chilean Chemical Society
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3049-3053
  • Keywords: Aripiprazole, dehydroaripiprazole, UHPLC, rat plasma, validation, protein precipitation, LC-MS/MS METHOD, PERFORMANCE LIQUID-CHROMATOGRAPHY, TANDEM MASS-SPECTROMETRY, SIMULTANEOUS QUANTIFICATION, QUANTITATIVE-DETERMINATION, CAPILLARY-ELECTROPHORESIS, ESI-MS, VALIDATION, METABOLITE, BRAIN
  • Anadolu University Affiliated: Yes

Abstract

A new, simple, specific, and rapid ultra high performance liquid chromatography method was developed and validated for the determination of aripiprazole and its active metabolite dehydroaripiprazole in rat plasma. The analysis was performed on a Zorbax Eclipse Plus C18 (50 mm × 2.1 mm, 1.8 μm particles) column using gradient elution with a mobile phase consisting of acetonitrile and acetate buffer (30 mM, pH 5). Plasma samples were analyzed after a simple, one-step protein precipitation with acetonitrile. The method was validated and the specificity, linearity, limit of detection, limit of quantitation, precision, accuracy, recoveries, matrix effect, stability and robustness were determined. The analytes and internal standard were separated in 3.5 min and the total analysis time including the clean-up step was 8 min. Limit of detection was 0.012 μg mL-1 and 0.009 μg mL-1 for aripiprazole and dehydroaripiprazole, respectively. Limit of quantitation was 0.039 μg mL-1 and 0.029 μg mL-1 for aripiprazole and dehydroaripiprazole, respectively. The intra- and inter-day assay variability was less than 2% for the analytes. The proposed method is rapid, reproducible and accurate to quantify both aripiprazole and dehydroaripiprazole. It involves a simple plasma deproteination technique using one step protein precipitation with acetonitrile. This validated method was successfully used to quantify plasma concentrations of the analytes in rat plasma.