Aripiprazole is an atypical antipsychotic that has serotonin 5-HT1A-receptor partial agonist and 5-HT2A-receptor antagonist properties as well as being a partial agonist at dopamine D2 receptors. It is used in the management of schizophrenia and in acute manic or mixed episodes associated with bipolar disorder in adults over 18 years of age [1].
A bioanalytical method was developed and validated according to Food and Drug Administration (FDA) [2] and European Medicines Agency (EMA) [3] guidelines with the OECD Principles of Good Laboratory Practice (GLP), to study pharmacokinetics of aripiprazole. The method was based on liquid-liquid extraction of aripiprazole with n hexane/izopropanol mixture, followed by reversed-phase liquid chromatography. Positive electrospray ionization mass spectrometry in single ion monitoring mode was applied as the detector. Isotope labelled aripiprazole was used as internal standard. No matrix effects and no back-conversion of dehydro-aripiprazole to aripiprazole were observed. Calibration curve, fitted to 1/x2 weighted linear regression model, was linear in the range of 1.0 – 80.0 ng/mL. Extraction recoveries for both aripiprazole and internal standard were approximately 75–80%. The method was successfully validated and applied in pharmacokinetic study in humans after a oral administration of aripiprazole.
[1] T. Swainston Harrison, C. M. Perry, Aripiprazole - A Review of its Use in Schizophrenia and Schizoaffective Disorder, Drugs, 64, 2004, 1715-1736
[2] Guidance for Industry. Bioanalytical Method Validation. U.S. Department of Health and Human Services. Food and Drug Administration. Center for Drug Evaluation and Research (CDER). Center for Veterinary Medicine (CVM). May 2001.
[3] Guideline on bioanalytical method validation. European Medicines Agency (EMEA/CHMP/EWP/192217/2009). London, 21 July 2011.
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