Quantification of Human Plasma-Busulfan Concentration by Liquid Chromatography-Tandem Mass Spectrometry.
- Author:
Soo Young MOON
1
;
Min Kyoo LIM
;
Susie HONG
;
Yongbum JEON
;
Minje HAN
;
Sang Hoon SONG
;
Kyoung Soo LIM
;
Kyung Sang YU
;
In Jin JANG
;
Ji Won LEE
;
Hyoung Jin KANG
;
Junghan SONG
Author Information
- Publication Type:Original Article ; Research Support, Non-U.S. Gov't
- Keywords: Busulfan; Drug monitoring; Tandem mass spectrometry; Liquid chromatography; Hematopoietic stem cell transplantation
- MeSH: Busulfan/*blood/standards; Child; Child, Preschool; *Chromatography, High Pressure Liquid/standards; Hematopoietic Stem Cell Transplantation; Humans; Infant; Quality Control; Reference Standards; *Tandem Mass Spectrometry/standards
- From:Annals of Laboratory Medicine 2014;34(1):7-14
- CountryRepublic of Korea
- Language:English
- 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 -20degrees C and -80degrees C, but decreased by 25% when the plasma was stored for 24 hr at room temperature, and by <5% in 24 hr at 4degrees C. 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.
