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 0.5mL/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 5μL 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 72h in the autosampler and the high quality control of 9-OH-risperidone was stable for 48h. 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.

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Keywords Antipsychotic drugs, Pharmacokinetics, children, Therapeutic drug monitoring, UPLC-MS/MS
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Journal Biomedical Chromatography
Wijma, R.A, van der Nagel, B.C, Dierckx, B, Dieleman, G.C, Touw, D.J, van Gelder, T, & Koch, B.C.P. (2016). Identification and quantification of the antipsychotics risperidone, aripiprazole, pipamperone and their major metabolites in plasma using ultra-high performance liquid chromatography-mass spectrometry. Biomedical Chromatography, 30(6), 794–801. doi:10.1002/bmc.3610