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

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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

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References

  1. Buggia I, Locatelli F, Regazzi MB, Zecca M (1994) Busulfan. Ann Pharmacother 28:1055–1062

    CAS  PubMed  Google Scholar 

  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 56:5533–5546

    CAS  PubMed  Google Scholar 

  3. Brookes P, Lawley PD (1960) The reaction of mustard gas with nucleic acids in vitro and in vivo. Biochem J 77:478–484

    PubMed Central  CrossRef  CAS  PubMed  Google Scholar 

  4. Kohn KW, Hartley JA, Mattes WB (1987) Mechanisms of DNA sequence selective alkylation of guanine-N7 positions by nitrogen mustards. Nucleic Acids Res 15:10531–10549

    PubMed Central  CrossRef  CAS  PubMed  Google Scholar 

  5. Hurley LH (2002) DNA and its associated processes as targets for cancer therapy. Nat Rev Cancer 2:188–200

    CrossRef  CAS  PubMed  Google Scholar 

  6. Newbold RF, Warren W, Medcalf AS, Amos J (1980) Mutagenicity of carcinogenic methylating agents is associated with a specific DNA modification. Nature 283:596–599

    CrossRef  CAS  PubMed  Google Scholar 

  7. Slattery JT, Risler LJ (1998) Therapeutic monitoring of busulfan in hematopoietic stem cell transplantation. Ther Drug Monit 20:543–549

    CrossRef  CAS  PubMed  Google Scholar 

  8. GlaxoSmithKline, Research Triangle Park, NC 27709. 2003

    Google Scholar 

  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. 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 16:31–42

    CAS  PubMed  Google Scholar 

  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 34:7–14

    PubMed Central  CrossRef  CAS  PubMed  Google Scholar 

  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 37:319–324

    CrossRef  CAS  PubMed  Google Scholar 

  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 428:357–361

    CrossRef  CAS  PubMed  Google Scholar 

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Correspondence to Loralie J. Langman Ph.D. .

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Langman, L.J., Danso, D., Robert, E., Jannetto, P.J. (2016). High-Throughput Quantitation of Busulfan in Plasma Using Ultrafast Solid-Phase Extraction Tandem Mass Spectrometry (SPE-MS/MS). In: Garg, U. (eds) Clinical Applications of Mass Spectrometry in Drug Analysis. Methods in Molecular Biology, vol 1383. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3252-8_10

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  • DOI: https://doi.org/10.1007/978-1-4939-3252-8_10

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3251-1

  • Online ISBN: 978-1-4939-3252-8

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