A fast and simple assay for busulfan in serum or plasma by liquid chromatography–tandem mass spectrometry using turbulent flow online extraction technology

Busulfan is used in myeloablative preparation regimens for hematopoietic bone marrow transplantation. Due to its narrow therapeutic range therapeutic drug monitoring of busulfan is recommended. In this study a fast and simple method for measuring busulfan in serum or plasma by liquid chromatography–...

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Veröffentlicht in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2010-12, Vol.878 (31), p.3255-3258
Hauptverfasser: Bunch, Dustin R., Heideloff, Courtney, Ritchie, James C., Wang, Sihe
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container_issue 31
container_start_page 3255
container_title Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
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creator Bunch, Dustin R.
Heideloff, Courtney
Ritchie, James C.
Wang, Sihe
description Busulfan is used in myeloablative preparation regimens for hematopoietic bone marrow transplantation. Due to its narrow therapeutic range therapeutic drug monitoring of busulfan is recommended. In this study a fast and simple method for measuring busulfan in serum or plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS) has been developed utilizing turbulent flow online extraction technology. Serum or plasma was mixed with acetonitrile containing d 8-busulfan. After centrifugation the supernatant was injected onto a turbulent flow preparatory column then transferred to a C18 analytical column monitored by a tandem mass spectrometer set at positive electrospray ionization. The analytical cycle time was 4.0 min. The method was linear from 0.15 to 41.90 μmol/L with an accuracy of 87.9–103.0%. Inter- and intra-assay CVs across four concentration levels were 2.1–7.8%. No significant carryover or ion suppression was observed. No interference was observed from commercial control materials containing more than 100 compounds. Comparison with a well established LC–MS/MS method using patient specimens ( n = 45) showed a mean bias 1.3% with Deming regression of slope 1.02, intercept −0.02 μmol/L, and a linear correlation coefficient 0.9883. The LC–MS/MS method coupled with turbulent flow online sample cleaning technology described here offers reliable busulfan quantitation in serum or plasma with minimum manual sample preparation and was fully validated for clinical use.
doi_str_mv 10.1016/j.jchromb.2010.10.003
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Due to its narrow therapeutic range therapeutic drug monitoring of busulfan is recommended. In this study a fast and simple method for measuring busulfan in serum or plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS) has been developed utilizing turbulent flow online extraction technology. Serum or plasma was mixed with acetonitrile containing d 8-busulfan. After centrifugation the supernatant was injected onto a turbulent flow preparatory column then transferred to a C18 analytical column monitored by a tandem mass spectrometer set at positive electrospray ionization. The analytical cycle time was 4.0 min. The method was linear from 0.15 to 41.90 μmol/L with an accuracy of 87.9–103.0%. Inter- and intra-assay CVs across four concentration levels were 2.1–7.8%. No significant carryover or ion suppression was observed. No interference was observed from commercial control materials containing more than 100 compounds. Comparison with a well established LC–MS/MS method using patient specimens ( n = 45) showed a mean bias 1.3% with Deming regression of slope 1.02, intercept −0.02 μmol/L, and a linear correlation coefficient 0.9883. 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B, Analytical technologies in the biomedical and life sciences</title><addtitle>J Chromatogr B Analyt Technol Biomed Life Sci</addtitle><description>Busulfan is used in myeloablative preparation regimens for hematopoietic bone marrow transplantation. Due to its narrow therapeutic range therapeutic drug monitoring of busulfan is recommended. In this study a fast and simple method for measuring busulfan in serum or plasma by liquid chromatography–tandem mass spectrometry (LC–MS/MS) has been developed utilizing turbulent flow online extraction technology. Serum or plasma was mixed with acetonitrile containing d 8-busulfan. After centrifugation the supernatant was injected onto a turbulent flow preparatory column then transferred to a C18 analytical column monitored by a tandem mass spectrometer set at positive electrospray ionization. The analytical cycle time was 4.0 min. The method was linear from 0.15 to 41.90 μmol/L with an accuracy of 87.9–103.0%. Inter- and intra-assay CVs across four concentration levels were 2.1–7.8%. No significant carryover or ion suppression was observed. No interference was observed from commercial control materials containing more than 100 compounds. Comparison with a well established LC–MS/MS method using patient specimens ( n = 45) showed a mean bias 1.3% with Deming regression of slope 1.02, intercept −0.02 μmol/L, and a linear correlation coefficient 0.9883. The LC–MS/MS method coupled with turbulent flow online sample cleaning technology described here offers reliable busulfan quantitation in serum or plasma with minimum manual sample preparation and was fully validated for clinical use.</description><subject>Acetonitriles - chemistry</subject><subject>Analysis</subject><subject>Analytical, structural and metabolic biochemistry</subject><subject>Biological and medical sciences</subject><subject>Busulfan</subject><subject>Busulfan - blood</subject><subject>Chemical Fractionation - methods</subject><subject>Chromatography</subject><subject>Chromatography, Liquid - methods</subject><subject>Drug Monitoring</subject><subject>Fluid dynamics</subject><subject>Fluid flow</subject><subject>Fundamental and applied biological sciences. 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subjects Acetonitriles - chemistry
Analysis
Analytical, structural and metabolic biochemistry
Biological and medical sciences
Busulfan
Busulfan - blood
Chemical Fractionation - methods
Chromatography
Chromatography, Liquid - methods
Drug Monitoring
Fluid dynamics
Fluid flow
Fundamental and applied biological sciences. Psychology
General pharmacology
Humans
Least-Squares Analysis
Liquid chromatography
Medical sciences
On-line systems
Online
Pharmacology. Drug treatments
Reproducibility of Results
Serums
Spectrometry, Mass, Electrospray Ionization
Tandem mass spectrometry
Tandem Mass Spectrometry - methods
Turbulence
Turbulent flow
title A fast and simple assay for busulfan in serum or plasma by liquid chromatography–tandem mass spectrometry using turbulent flow online extraction technology
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