A gas-chromatographic assay method for busulfan with sensitivity for test dose therapeutic monitoring.
A gas-chromatographic assay method was developed and validated for determination of busulfan in human plasma for test dose therapeutic drug monitoring. Busulfan and the internal standard (1,6-bis-(methanesulfonyloxy)hexane) were extracted from plasma samples and derivatized with 2,3,5,6-tetrafluorothiophenol prior to gas chromatographic determination. The 63Ni electron-capture detector provided a limit of quantitation of 0.0100 micrograms ml-1 busulfan in plasma with a linear response over the concentration range 0.0100-0.400 micrograms ml-1. Extraction and derivatization yields were 85.3%-91.0% and greater than 95%, respectively. Assay specificity for busulfan in the presence of potential metabolites was demonstrated. Potentially co-administered drugs gave no response under the sample preparation and chromatographic conditions described for quantification of busulfan. The applicability of this assay to the individualization of busulfan therapy based on a 2 mg test dose is discussed.
Burns
R B
RB
Division of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada.
Heggie
J R
JR
Embree
L
L
D018906:Antineoplastic Agents, Alkylating / Q000032:analysis / Q000097:blood* / Q000302:isolation & purification; D002066:Busulfan / Q000032:analysis / Q000097:blood* / Q000302:isolation & purification; D002138:Calibration; D002849:Chromatography, Gas / Q000379:methods*; D016903:Drug Monitoring; D006801:Humans; D010636:Phenols / Q000737:chemistry; D012044:Regression Analysis; D015203:Reproducibility of Results; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013876:Thiophenes / Q000097:blood / Q000737:chemistry
D018906:Antineoplastic Agents, Alkylating; D010636:Phenols; D013438:Sulfhydryl Compounds; D013876:Thiophenes; C081141:2,3,5,6-tetrafluorobenzenethiol; D002066:Busulfan; C013693:sulfolane