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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 sta- bility were evaluated. The range of plasma busulfan concentration was obtained by ana- lyzing 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°C and -80°C, but decreased by 25% when the plasma was stored for 24 hr at room temperature, and by <5% in 24 hr at 4°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.
