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Ultratrace voltammetric determination of DNA-bound platinum in patients after administration of oxaliplatin

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Abstract

Oxaliplatin, a novel diaminocyclohexane-platinum complex, is used for the treatment of metastatic colorectal cancer. The amount of DNA-adduct formation of this drug in white blood cells of patients is determined after isolation of the DNA by density gradient centrifugation and a four-step solid phase extraction procedure. DNA is quantified by UV spectrometry, and platinum is determined after mineralization of the DNA sample by adsorptive stripping voltammetry (formazone method). It is possible to determine Pt-nucleotide ratios in clinical samples down to five Pt atoms in 108 nucleotides, and the dynamic range of the method covers three orders of magnitude. An absolute amount of 25 μg of DNA is sufficient for such measurements. With the method described, the time-dependent formation of oxaliplatin DNA adducts can be monitored in clinical studies, which may help us to understand inter-individual differences in the responses of patients to oxaliplatin-based therapy.

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Acknowledgement

We gratefully acknowledge the financial support of Sanofi-Synthelabo GmbH.

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Authors and Affiliations

  1. Institut für Spektrochemie und Angewandte Spektroskopie, Bunsen-Kirchhoff-Str. 11, 44139, Dortmund, Germany

    G. Weber & J. Messerschmidt

  2. Pharmazeutisches Institut, Klinische Pharmazie, Universität Bonn, An der Immenburg 4, 53121, Bonn, Germany

    A. C. Pieck & U. Jaehde

  3. Sana Klinikum Remscheid GmbH, Burger Str. 211, 42859, Remscheid, Germany

    A. M. Junker & A. Wehmeier

Authors
  1. G. Weber
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  2. J. Messerschmidt
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  3. A. C. Pieck
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  4. A. M. Junker
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  5. A. Wehmeier
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  6. U. Jaehde
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Corresponding author

Correspondence to G. Weber.

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Weber, G., Messerschmidt, J., Pieck, A.C. et al. Ultratrace voltammetric determination of DNA-bound platinum in patients after administration of oxaliplatin. Anal Bioanal Chem 380, 54–58 (2004). https://doi.org/10.1007/s00216-004-2723-x

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  • DOI: https://doi.org/10.1007/s00216-004-2723-x

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