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Type: Journal article
Title: Sensitive and rapid quantification of busulfan in small plasma volumes by liquid chromatography-electrospray mass spectrometry
Author: Murdter, T.
Coller, J.
Claviez, A.
Schonberger, F.
Hofmann, U.
Dreger, P.
Schwab, M.
Citation: Clinical Chemistry (Washington, DC): international journal of molecular diagnostics and laboratory medicine, 2001; 47(8):1437-1442
Publisher: Amer Assoc Clinical Chemistry
Issue Date: 2001
ISSN: 0009-9147
Statement of
Thomas E. Mürdter, Janet Coller, Alexander Claviez, Frank Schönberger, Ute Hofmann, Peter Dreger and Matthias Schwab
Abstract: BACKGROUND: High-dose busulfan is widely used in conditioning regimens before hematopoietic stem cell transplantation in both adults and children. Large interindividual variability in pharmacokinetics after oral administration has been reported; therefore, therapeutic drug monitoring of busulfan may decrease the incidence of drug-related toxicity (for example, hepatic venoocclusive disease) and may also improve therapeutic efficacy. METHODS: Busulfan concentrations were quantified using 200 µL of plasma and liquid–liquid extraction with diethyl ether after the addition of [2H8]busulfan as the internal standard. Separation and detection of busulfan and [2H8]busulfan were achieved with a LUNA C8 column (5 µm; 150 x 2 mm i.d.) at 30 °C, a HP 1100 liquid chromatography system, and a HP 1100 single-quadrupole mass spectrometer. Busulfan and [2H8]busulfan were detected as ammonium adducts in selected-ion monitoring mode at m/z 264.2 and 272.2, respectively. RESULTS: The calibration curve was linear at 5–2000 µg/L busulfan. Intra- and interassay imprecision (CV) and bias were both <11%. The limits of detection and quantification were 2 and 5 µg/L, respectively. Extraction recovery of busulfan was >87%. Analysis of pharmacokinetics in four patients receiving high-dose busulfan indicated that minimum busulfan concentrations before the next dose were 405–603 µg/L, with no interference observed. CONCLUSIONS: The new rapid and sensitive liquid chromatographic–mass spectrometric assay is an appropriate method for quantification of busulfan in human plasma, making therapeutic drug monitoring of busulfan faster and easier in clinical practice
Keywords: Humans
Antineoplastic Agents, Alkylating
Drug Monitoring
Chromatography, Liquid
Spectrometry, Mass, Electrospray Ionization
Reproducibility of Results
Middle Aged
Description: © 2001 American Association for Clinical Chemistry, Inc.
DOI: 10.1093/clinchem/47.8.1437
Published version:
Appears in Collections:Aurora harvest 2
Pharmacology publications

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