Determination of treosulfan and fludarabine in plasma by turbulent flow liquid chromatography-tandem mass spectrometry (TFLC-MS/MS) Journal Article


Authors: Hutcherson, S. M.; Schofield, R. C.; Carlow, D. C.
Article Title: Determination of treosulfan and fludarabine in plasma by turbulent flow liquid chromatography-tandem mass spectrometry (TFLC-MS/MS)
Abstract: Treosulfan is a structural analog of the alkylating agent busulfan which has been shown in clinical trials to exhibit comparable myeloablative activity while causing fewer serious side effects. Treosulfan is currently being considered for FDA approval in combination with fludarabine, one of the most commonly used myeloablative agents, as a conditioning regimen prior to hematopoietic stem cell transplantation (HSCT). Because plasma concentrations of both treosulfan and fludarabine exhibit significant interindividual variability, therapeutic drug monitoring (TDM) is indicated to ensure dosages are administered that maximize efficacy while minimizing toxicity. In this chapter, we describe a rapid, accurate assay to detect treosulfan and fludarabine simultaneously in human plasma using turbulent flow liquid chromatography coupled to electrospray ionization tandem mass spectrometry (TFLC-ESI-MS/MS). Treosulfan and fludarabine are extracted from only 100 μL of acidified plasma via protein precipitation with methanol containing isotope-labeled internal standards. The extract is injected into the TFLC-ESI-MS/MS system, and the analytes are quantified using multiple reaction monitoring and a six-point calibration curve. © 2024, The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.
Keywords: controlled study; busulfan; fludarabine; multiple reaction monitoring; mass spectrometry; tandem mass spectrometry; drug blood level; high performance liquid chromatography; chromatography, liquid; liquid chromatography; drug determination; plasma; drug degradation; linear regression analysis; electrospray mass spectrometry; procedures; treosulfan; humans; human; therapeutic drug monitoring; turbulent flow liquid chromatography; retention time; method validation; turbulent flow liquid chromatography-mass spectrometry
Journal Title: Methods in Molecular Biology
Volume: 2737
ISSN: 1064-3745
Publisher: Humana Press Inc  
Date Published: 2024-01-01
Start Page: 453
End Page: 463
Language: English
DOI: 10.1007/978-1-0716-3541-4_42
PROVIDER: scopus
PUBMED: 38036846
DOI/URL:
Notes: Chapter 42 in "Clinical Applications of Mass Spectrometry in Drug Analysis. 2nd Ed" (ISBN: 978-1-0716-3540-7) -- The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Doesn't list a corresponding author -- Source: Scopus
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  1. Dean Christian Carlow
    42 Carlow