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 Ni-63 electron-capture detector provided a limit of quantitation of 0.0100 mu g ml(-1) busulfan in plasma with a linear response over the concentration range 0.0100-0.400 mu g 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.