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Therapeutic Monitoring of Aripiprazole by HPLC with Column-Switching and Spectrophotometric Detection

¹ Department of Psychiatry, University of Mainz, Mainz, Germany;² Division of Neurochemistry, Department of Psychiatry, Medical University of Innsbruck, Innsbruck, Austria;³ Department of Psychiatry, Heinrich-Heine-University, Duesseldorf, Germany;

^aaddress correspondence to this author at: Department of Psychiatry, University of Mainz, Untere Zahlbacher Strasse 8, D-55131 Mainz, Germany; fax 49-6131-176789, e-mail hiemke@mail.uni-mainz.de

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Aripiprazole is a novel atypical antipsychotic drug for the treatment of schizophrenia and schizoaffective disorders (1)(2)(3). The drug is metabolized by the cytochrome P450 isoenzymes 3A4 and 2D6 (4). Because of high interindividual variability in the expression of these enzymes, the aripiprazole concentration varies among healthy individuals after administration of the drug (5). In patients, insufficient response or side effects, such as somnolence, akathisia, or nausea, may result from too low or too high drug concentrations. Therapeutic drug monitoring (TDM), which is established practice for many antipsychotic drugs (6)(7), may be helpful for patients treated with aripiprazole. We measured aripiprazole by HPLC with column-switching and ultraviolet detection, based on a previously reported method for TDM of the antidepressant reboxetine (8).

Pure drug was not available; we therefore incubated tablets containing 15 mg of aripiprazole base (Abilify®; Bristol-Myers Squibb/Otsuka Pharmaceuticals) for several days in the dark at room temperature in 15 mL per tablet of methanol (LiChrosolve; Merck) or ultrapure water adjusted to pH 2 with 0.1 mol/L HCl. Before chromatographic analysis, suspensions were shaken and cleared by centrifugation (3000g for 5 min). Maximum solution was attained within the first 24 h. Because the mean drug concentrations in samples diluted to concentrations of 100, 200, or 500 µg/L differed little (2.7%; range, –7% to 10%) between methanol and water solutions, complete solution by methanol was assumed. Methanolic solutions were used for the preparation of calibrator samples with 6 concentrations between 50 and 500 µg/L and quality-control samples containing 50, 250, or 400 µg/L, prepared by supplementing drug-free plasma with aripiprazole. Perphenazine base from Sigma was used as internal standard in a final concentration of 0.0615 g/L.

Blood for serum preparation was collected from 27 . . . [Full Text of this Article]

The following articles in journals at HighWire Press have cited this article:

				G. Grunder, C. Fellows, H. Janouschek, T. Veselinovic, C. Boy, A. Brocheler, K. M. Kirschbaum, S. Hellmann, K. M. Spreckelmeyer, C. Hiemke, et al. Brain and Plasma Pharmacokinetics of Aripiprazole in Patients With Schizophrenia: An [18F]Fallypride PET Study Am J Psychiatry, August 1, 2008; 165(8): 988 - 995. [Abstract] [Full Text] [PDF]