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Quantitative determination of methylphenidate in plasma by gas chromatography negative ion chemical ionisation mass spectrometry using o-(pentafluorobenzyloxycarbonyl)-benzoyl derivatives

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Abstract

The use of a novel electrophoric derivatisation reagent, o-(pentafluorobenzyloxycarbonyl)-benzoyl chloride, for the quantitative determination of methylphenidate in plasma is described. The drug can be quantitatively measured down to 72 pg/mL plasma using only 250 μL of sample due to the extraordinary sensitivity of the derivatives under negative ion chemical ionisation mass spectrometry. Plasma samples were made alkaline with carbonate buffer and treated with extraction solvent n-hexane and reagent solution for 30 min, which, after concentration, was measured by GC-NICI-MS. The method is rapid as extraction and derivatisation occur in one single step. A stable isotope-labelled internal standard was used and its synthesis described. Full validation data are given to demonstrate the usefulness of the assay, including specificity, linearity, accuracy and precision, long-term stability, short-term stability, freeze–thaw stability, stock solution stability, autosampler stability, aliquot analysis, robustness, matrix effect, and prospective analytical batch size accuracy. The method has been successfully applied to pharmacokinetic profiling of the drug after oral application.

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Authors and Affiliations

  1. Division of Analytical Biochemistry and Mass Spectrometry, University Children’s Hospital, Auenbruggerplatz 34/2, 8036, Graz, Austria

    Hans J. Leis & Werner Windischhofer

  2. Consultancy Services for Bioequivalence and Bioavailability Studies, BEBAC, Neubaugasse 36/11, 1070, Vienna, Austria

    Helmut Schütz

  3. Research Unit of Osteology and Analytical Mass Spectrometry, University Children’s Hospital, Auenbruggerplatz 34/2, 8036, Graz, Austria

    Hans J. Leis

Authors
  1. Hans J. Leis
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  2. Helmut Schütz
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  3. Werner Windischhofer
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Correspondence to Hans J. Leis.

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Published in the special issue on Analytical Sciences in Austria with Guest Editors G. Allmaier, W. Buchberger and K. Francesconi.

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Leis, H.J., Schütz, H. & Windischhofer, W. Quantitative determination of methylphenidate in plasma by gas chromatography negative ion chemical ionisation mass spectrometry using o-(pentafluorobenzyloxycarbonyl)-benzoyl derivatives. Anal Bioanal Chem 400, 2663–2670 (2011). https://doi.org/10.1007/s00216-011-5048-6

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  • DOI: https://doi.org/10.1007/s00216-011-5048-6

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