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Clinical Chemistry 44: 2506-2510, 1998;
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(Clinical Chemistry. 1998;44:2506-2510.)
© 1998 American Association for Clinical Chemistry, Inc.

Drug Monitoring and Toxicology

Routine analysis of plasma busulfan by gas chromatography–mass fragmentography

Wai-Kai Lai1, Chi-Pui Pang1,a, Lap-Kay Law1, Raymond Wong2, Chi-Kong Li2 and Patrick Man-Pan Yuen2

Departments of
1 Chemical Pathology and
2 Paediatrics, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong.
a Address correspondence to this author at: Department of Opthalmology and Visual Sciences, the Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. Fax: 852-26482943; e-mail cppang{at}cuhk.edu.hk.

Busulfan (BU) is a widely used alkylating agent for antineoplastic therapy and marrow ablation in preparation for bone marrow transplantation (BMT). High-dose BU often leads to successful preparation and low relapse but is associated with veno-occlusive disease of liver. We established a protocol to determine postdosage plasma BU concentrations by gas chromatography–mass fragmentography in an attempt to relate clinical outcome to plasma BU concentrations. We used nonisotopic pusulfan as the internal standard. After extraction into ethyl acetate, BU and pusulfan were iodinated into 1,4-diiodobutane and 1,5-diiodopentane, respectively. Gas chromatography–mass spectrometry (GC–MS) analysis was carried out on an Hewlett–Packard (HP) 5890II gas chromatograph with a 30-m 100% methyl silicon narrow bore, fused-silica capillary column interfaced with an HP 5970A mass spectrometer. Helium was the carrier gas. The sample molecules were identified by total ion monitoring and quantified by selective ion monitoring of m/z 183 and 197. The calibration curve was linear to 4 mg/L. The limit of quantification was 0.04 mg/L, and the analytical recovery was ~97%. The within-day and between-day imprecision (CV) was <6% and 9%, respectively. In a preliminary study of 12 children, the BU areas under the BU-time curve were 616–949 µmol · min/L after the first dose and 793-1143 µmol · min/L after the fifth dose. We conclude that the GC–MS procedure is suitable for routine analysis of plasma BU.




The following articles in journals at HighWire Press have cited this article:


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 Clin. Chem.Home page
T. E. Murdter, J. Coller, A. Claviez, F. Schonberger, U. Hofmann, P. Dreger, and M. Schwab
Sensitive and Rapid Quantification of Busulfan in Small Plasma Volumes by Liquid Chromatography-Electrospray Mass Spectrometry
Clin. Chem., August 1, 2001; 47(8): 1437 - 1442.
[Abstract] [Full Text] [PDF]


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