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A novel method for quantification of sulfolane (a metabolite of busulfan) in plasma by gas chromatography–tandem mass spectrometry

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Abstract

The role of busulfan (Bu) metabolites in the adverse events seen during hematopoietic stem cell transplantation and in drug interactions is not explored. Lack of availability of established analytical methods limits our understanding in this area. The present work describes a novel gas chromatography–tandem mass spectrometric assay for the analysis of sulfolane (Su) in plasma of patients receiving high-dose Bu. Su and Bu were extracted from a single 100 μL plasma sample by liquid–liquid extraction. Bu was separately derivatized with 2,3,5,6-tetrafluorothiophenolfluorinated agent. Mass spectrometric detection of the analytes was performed in the selected reaction monitoring mode on a triple quadrupole instrument after electronic impact ionization. Bu and Su were analyzed with separate chromatographic programs, lasting 5 min each. The assay for Su was found to be linear in the concentration range of 20–400 ng/mL. The method has satisfactory sensitivity (lower limit of quantification, 20 ng/mL) and precision (relative standard deviation less than 15 %) for all the concentrations tested with a good trueness (100 ± 5 %). This method was applied to measure Su from pediatric patients with samples collected 4 h after dose 1 (n = 46), before dose 7 (n = 56), and after dose 9 (n = 54) infusions of Bu. Su (mean ± SD) was detectable in plasma of patients 4 h after dose 1, and higher levels were observed after dose 9 (249.9 ± 123.4 ng/mL). This method may be used in clinical studies investigating the role of Su on adverse events and drug interactions associated with Bu therapy.

Overall sample preparation procedure for quantification of sulfolane and busulfan in plasma from patients receiving higher doses of busulfan

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Acknowledgments

We are thankful to the patients and their parents who consented to participate to this study. This study was supported by the grants of the CANSEARCH Foundation, The Hans Wilsdorf, the Télémaque Foundations, and the Geneva Cancer League.

Conflicts of interest

The authors declare no competing financial interests.

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Authors and Affiliations

  1. Unit of Toxicology, University Center of Legal Medicine, 1211, Geneva, Switzerland

    François Versace, Patrice Mangin & Christian Staub

  2. Department of Pediatrics, Onco-hematology Unit, University Hospital of Geneva, 1211, Geneva, Switzerland

    Chakradhara Rao S. Uppugunduri, Fabienne Gumy-Pause & Marc Ansari

  3. Department of Pharmacology, CHU Sainte Justine, University of Montréal, H3C 3J7, Montréal, Canada

    Maja Krajinovic & Yves Théorêt

Authors
  1. François Versace
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  2. Chakradhara Rao S. Uppugunduri
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  3. Maja Krajinovic
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  4. Yves Théorêt
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  5. Fabienne Gumy-Pause
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  6. Patrice Mangin
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  7. Christian Staub
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  8. Marc Ansari
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Corresponding author

Correspondence to Marc Ansari.

Additional information

François Versace and Chakradhara Rao S Uppugunduri contributed equally to this work.

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Versace, F., Uppugunduri, C.R.S., Krajinovic, M. et al. A novel method for quantification of sulfolane (a metabolite of busulfan) in plasma by gas chromatography–tandem mass spectrometry. Anal Bioanal Chem 404, 1831–1838 (2012). https://doi.org/10.1007/s00216-012-6330-y

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  • DOI: https://doi.org/10.1007/s00216-012-6330-y

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