title: Identification and quantification of the antipsychotics risperidone, aripiprazole, pipamperone and their major metabolites in plasma using ultra-high performance liquid chromatography-mass spectrometry.
abstract: The antipsychotics risperidone, aripiprazole and pipamperone are frequently prescribed for the treatment in children with autism. The aim of this study was to validate an ultra-high performance liquid chromatography-mass spectrometry method for the quantification of these antipsychotics in plasma. An ultra-high performance liquid chromatography-mass spectrometry assay was developed for the determination of the drugs and metabolites. Gradient elution was performed on a reversed-phase column with a mobile phase consisting of ammonium acetate, formic acid in methanol or in Milli-Q ultrapure water at a flow rate of 0.5 mL/min. The method was validated according to the US Food and Drug Administration guidelines. The analytes were found to be stable enough after reconstitution and injection of only 5 μL improved the accuracy and precision in combination with the internal standard. Calibration curves of all five analytes were linear. All analytes were stable for at least 72 h in the autosampler and the high quality control of 9-OH-risperidone was stable for 48 h. The method allows quantification of all analytes. The advantage of this method is the combination of a minimal injection volume, a short run-time, an easy sample preparation method and the ability to quantify all analytes in one run. Copyright © 2015 John Wiley & Sons, Ltd.
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, Postal Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Rixt A
authors.initials: RA
authors.lastname: Wijma
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, Postal Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Bart C H
authors.initials: BC
authors.lastname: van der Nagel
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, Postal box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Bram
authors.initials: B
authors.lastname: Dierckx
authors.affiliation: Department of Child and Adolescent Psychiatry, Erasmus MC, Postal box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Gwen C
authors.initials: GC
authors.lastname: Dieleman
authors.affiliation: Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen, Postal Box 30.001, 9700 RB, Groningen, The Netherlands.
authors.forename: Daan J
authors.initials: DJ
authors.lastname: Touw
authors.affiliation: Department of Hospital Pharmacy and Internal Medicine, Erasmus MC, Postal Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.affiliation: Department of Hospital Pharmacy, Erasmus MC, Postal Box 2040, 3000 CA, Rotterdam, The Netherlands.
authors.forename: Birgit C P
authors.initials: BC
authors.lastname: Koch
mesh_terms: D014150:Antipsychotic Agents / Q000097:blood*; D000068180:Aripiprazole / Q000097:blood; D002090:Butyrophenones / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D012015:Reference Standards; D015203:Reproducibility of Results; D018967:Risperidone / Q000097:blood; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D014150:Antipsychotic Agents; D002090:Butyrophenones; C005569:pipamperone; D000068180:Aripiprazole; D018967:Risperidone
keywords: UPLC-MS/MS; antipsychotic drugs; pharmacokinetics; children; therapeutic drug monitoring