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High-Throughput Quantitation of Busulfan in Plasma Using Ultrafast Solid-Phase Extraction Tandem Mass Spectrometry (SPE-MS/MS)

  • Loralie J. LangmanEmail author
  • Darlington Danso
  • Enger Robert
  • Paul J. Jannetto
Part of the Methods in Molecular Biology book series (MIMB, volume 1383)

Abstract

Busulfan is a commonly used antineoplastic agent to condition/ablate bone marrow cells before hematopoietic stem cell transplant. While intravenous (IV) formulations of busulfan are now available and have lower incidences of toxicity and treatment related mortality compared to oral dosing, it still displays large pharmacokinetic variability. As a result, studies have shown that therapeutic drug monitoring is clinically useful to minimize graft failure, disease reoccurrence, and toxicities like veno-occlusive disease and neurologic toxicity. Current methods for assaying busulfan include the use of GC/MS, HPLC, and LC-MS/MS. The clinical need for faster turnaround times and increased testing volumes has required laboratories to develop faster methods of analysis for higher throughput of samples. Therefore, we present a method for the quantification of busulfan in plasma using an ultrafast SPE-MS/MS which has much faster sample cycle times (<20 s per sample) and comparable analytical results to GC/MS.

Key words

Busulfan SPE-MS/MS AUC Pharmacokinetic monitoring 

References

  1. 1.
    Buggia I, Locatelli F, Regazzi MB, Zecca M (1994) Busulfan. Ann Pharmacother 28:1055–1062PubMedGoogle Scholar
  2. 2.
    Kohn KW (1996) Beyond DNA cross-linking: history and prospects of DNA-targeted cancer treatment--fifteenth Bruce F. Cain Memorial Award Lecture. Cancer Res 56:5533–5546PubMedGoogle Scholar
  3. 3.
    Brookes P, Lawley PD (1960) The reaction of mustard gas with nucleic acids in vitro and in vivo. Biochem J 77:478–484PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Kohn KW, Hartley JA, Mattes WB (1987) Mechanisms of DNA sequence selective alkylation of guanine-N7 positions by nitrogen mustards. Nucleic Acids Res 15:10531–10549PubMedCentralCrossRefPubMedGoogle Scholar
  5. 5.
    Hurley LH (2002) DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer 2:188–200CrossRefPubMedGoogle Scholar
  6. 6.
    Newbold RF, Warren W, Medcalf AS, Amos J (1980) Mutagenicity of carcinogenic methylating agents is associated with a specific DNA modification. Nature 283:596–599CrossRefPubMedGoogle Scholar
  7. 7.
    Slattery JT, Risler LJ (1998) Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit 20:543–549CrossRefPubMedGoogle Scholar
  8. 8.
    GlaxoSmithKline, Research Triangle Park, NC 27709. 2003Google Scholar
  9. 9.
    Baselt RC. Busulfan. In: Baselt RC, Ed. Disposition of toxic drugs and chemical in man. 9th ed. Foster, City, CA: Biomedical Publications; 2011. p. 218–220.Google Scholar
  10. 10.
    Slattery JT, Sanders JE, Buckner CD, Schaffer RL, Lambert KW, Langer FP, Anasetti C, Bensinger WI, Fisher LD, Appelbaum FR et al (1995) Graft-rejection and toxicity following bone marrow transplantation in relation to busulfan pharmacokinetics. Bone Marrow Transplant 16:31–42PubMedGoogle Scholar
  11. 11.
    Moon SY, Lim MK, Hong S, Jeon Y, Han M, Song SH, Lim KS, Yu KS, Jang IJ, Lee JW et al (2014) Quantification of human plasma-busulfan concentration by liquid chromatography-tandem mass spectrometry. Ann Lab Med 34:7–14PubMedCentralCrossRefPubMedGoogle Scholar
  12. 12.
    Danso D, Jannetto PJ, Enger R, Langman LJ (2015) High-throughput validated method for the quantitation of busulfan in plasma using ultrafast SPE-MS/MS. Ther Drug Monit 37:319–324CrossRefPubMedGoogle Scholar
  13. 13.
    Vassal G, Re M, Gouyette A (1988) Gas chromatographic-mass spectrometric assay for busulfan in biological fluids using a deuterated internal standard. J Chromatogr 428:357–361CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Loralie J. Langman
    • 1
    Email author
  • Darlington Danso
    • 1
  • Enger Robert
    • 1
  • Paul J. Jannetto
    • 1
  1. 1.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA

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