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Simultaneous quantification of ten cytotoxic drugs by a validated LC–ESI–MS/MS method

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Abstract

A liquid chromatography separation with electrospray ionisation and tandem mass spectrometry detection method was developed for the simultaneous quantification of ten commonly handled cytotoxic drugs in a hospital pharmacy. These cytotoxic drugs are cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. The chromatographic separation was carried out by RPLC in less than 21 min, applying a gradient elution of water and acetonitrile in the presence of 0.1% formic acid. MS/MS was performed on a triple quadrupole in selected reaction monitoring mode. The analytical method was validated to determine the limit of quantification (LOQ) and quantitative performance: lowest LOQs were between 0.25 and 2 ng mL−1 for the ten investigated cytotoxic drugs; trueness values (i.e. recovery) were between 85% and 110%, and relative standard deviations for both repeatability and intermediate precision were always inferior to 15%. The multi-compound method was successfully applied for the quality control of pharmaceutical formulations and for analyses of spiked samples on potentially contaminated surfaces.

Preparation of cytotoxic formulations at the Pharmacy of Geneva University Hospitals

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Acknowledgements

We kindly thank the Proteomics Core Facility at the Faculty of Medicine, University of Geneva (Switzerland) for the loan of the LC–MS/MS instrument.

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Authors and Affiliations

  1. Pharmacy, Geneva University Hospitals (HUG), 1211, Geneva, Switzerland

    Susanne Nussbaumer, Sandrine Fleury-Souverain, Farshid Sadeghipour & Pascal Bonnabry

  2. School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211, Geneva 4, Switzerland

    Susanne Nussbaumer, Denis F. Hochstrasser, Pascal Bonnabry & Jean-Luc Veuthey

  3. Swiss Centre for Applied Human Toxicology (SCAHT), 1211, Geneva, Switzerland

    Susanne Nussbaumer, Paola Antinori, Denis F. Hochstrasser, Jean-Luc Veuthey & Laurent Geiser

Authors
  1. Susanne Nussbaumer
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  2. Sandrine Fleury-Souverain
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  3. Paola Antinori
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  4. Farshid Sadeghipour
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  5. Denis F. Hochstrasser
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  6. Pascal Bonnabry
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  7. Jean-Luc Veuthey
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  8. Laurent Geiser
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Correspondence to Laurent Geiser.

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Nussbaumer, S., Fleury-Souverain, S., Antinori, P. et al. Simultaneous quantification of ten cytotoxic drugs by a validated LC–ESI–MS/MS method. Anal Bioanal Chem 398, 3033–3042 (2010). https://doi.org/10.1007/s00216-010-4243-1

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  • DOI: https://doi.org/10.1007/s00216-010-4243-1

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