Determination of plasma dexamethasone by chemical oxidation and electron capture negative ionization mass spectrometry.

A quantitative assay for dexamethasone in human plasma is described as based on methodology employing electron capture negative ionization mass spectrometry (ECNI/MS). The unique feature of this assay is the sample preparation involving chemical oxidation which transforms dexamethasone to a highly electrophilic species while not significantly affecting the electrophilic character of the biochemical matrix, thereby permitting selective and sensitive detection of the analyte. Optimized chemical procedures and instrumental parameters are described for the detection of oxidized dexamethasone. Finally, the newly developed methodology, based on gas chromatography/mass spectrometry (GC/MS) with ECNI, is evaluated by comparison with a conventional GC/MS assay using electron impact of an 11,17,21-tris-trimethylsilyl ether 20-enol-trimethylsilyl ether derivative of dexamethasone and with a radioimmunoassay in the analysis of pooled samples of human plasma containing widely varying concentrations of the drug as obtained from patients at different stages of the dexamethasone suppression test.