Rb. Burns et al., A GAS-CHROMATOGRAPHIC ASSAY-METHOD FOR BUSULFAN WITH SENSITIVITY FOR TEST DOSE THERAPEUTIC MONITORING, Journal of pharmaceutical and biomedical analysis, 13(9), 1995, pp. 1073-1078
A gas-chromatographic assay method was developed and validated for det
ermination of busulfan in human plasma for test dose therapeutic drug
monitoring. Busulfan and the internal standard (1,6-bis-(methanesulfon
yloxy)hexane) were extracted from plasma samples and derivatized with
2,3,5,6-tetrafluorothiophenol prior to gas chromatographic determinati
on. The Ni-63 electron-capture detector provided a limit of quantitati
on of 0.0100 mu g ml(-1) busulfan in plasma with a linear response ove
r the concentration range 0.0100-0.400 mu g ml(-1) Extraction and deri
vatization yields were 85.3%-91.0% and greater than 95%, respectively.
Assay specificity for busulfan in the presence of potential metabolit
es was demonstrated. Potentially co-administered drugs gave no respons
e under the sample preparation and chromatographic conditions describe
d for quantification of busulfan. The applicability;of this assay to t
he individualization of busulfan therapy based on a 2 mg test dose is
discussed.