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Quantification of human plasma-busulfan concentration by liquid chromatography-tandem mass spectrometry.

Abstract：

BACKGROUND:Busulfan, an alkylating agent administered prior to hematopoietic stem cell transplantation, has a narrow therapeutic range and wide variability in metabolism. We developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for rapid and accurate quantification of plasma busulfan. METHODS:Busulfan was separated and detected using an LC system containing a C18 column equipped with MS/MS. The sample was eluted with a mobile phase gradient for a total run time of 10 min. Plasma busulfan concentration was quantified against a 6-point standard curve in a multiple reaction monitoring mode at mass-to-charge (m/z) 264.1 > 151.1. Precision, recovery, matrix effect, linearity, detection capability, carryover, and stability were evaluated. The range of plasma busulfan concentration was obtained by analyzing samples from 9 children receiving busulfan. RESULTS:The coefficients of variation of within-run and within-laboratory precision were all below 5%. Recoveries were all within the range of 100-105%. Linearity was verified from 0 to 5,000 ng/mL. Limit of detection and limit of quantification were 1.56 and 25 ng/mL, respectively. Carryover rate was within allowable limits. Plasma busulfan concentration was stable for 2 weeks at -20℃ and -80℃, but decreased by 25% when the plasma was stored for 24 hr at room temperature, and by <5% in 24 hr at 4℃. The plasma busulfan concentrations were between 347 ng/mL and 5,076 ng/mL. CONCLUSIONS:Our method using LC-MS/MS enables highly accurate, reproducible, and rapid busulfan monitoring with minimal sample preparation. The method may also enable safe and proper dosage.

journal_name

Ann Lab Med

journal_title

Annals of laboratory medicine

authors

Moon SY,Lim MK,Hong S,Jeon Y,Han M,Song SH,Lim KS,Yu KS,Jang IJ,Lee JW,Kang HJ,Song J

doi

10.3343/alm.2014.34.1.7

keywords:

["Busulfan","Drug monitoring","Hematopoietic stem cell transplantation","Liquid chromatography","Tandem mass spectrometry"]

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

7-14

issue

1

eissn

2234-3806

issn

2234-3814

journal_volume

34

pub_type

杂志文章

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