Quantification of busulfan in plasma by gas chromatography-mass spectrometry following derivatization with tetrafluorothiophenol

Marie Helene Quernin, Balasubramanian Poonkuzhali, Christine Montes, Rajagopal Krishnamoorthy, David Dennison, Alok Srivastava, Etienne Vilmer, Mammen Chandy, Evelyne Jacqz-Aigrain

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Abstract

A specific and highly sensitive method has been developed for the determination of busulfan in plasma by gas chromatography-mass spectrometry using a deuterium-labeled busulfan (busulfan-d8) as internal standard. Plasma containing busulfan and busulfan-d8 were extracted with ethyl acetate and derivatized with 2,3,5,6-tetrafluorothiophenol prior to the monitoring of specific ions. The limit of quantification of the assay was 20 ng/ml and the calibration curve was linear over the range of 10 to 2000 ng/ml of derivatized busulfan. This method was in good agreement with the GC-MS assay using derivatization with sodium iodide and measuring diiodobutane. In addition, a pharmacokinetic study of busulfan was conducted in six children. The apparent oral clearance was 5.7 ± 1.9 ml/kg/min and the volume of distribution was 1.0 ± 0.4 l/kg and were similar to those previously reported in pediatric patients.

Original languageEnglish
Pages (from-to)47-56
Number of pages10
JournalJournal of Chromatography B: Biomedical Applications
Volume709
Issue number1
DOIs
Publication statusPublished - May 8 1998

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Keywords

  • Busulfan
  • Tetrafluorothiophenol

ASJC Scopus subject areas

  • Chemistry(all)

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