Detection of carbon-14 eluting from a capillary gas chromatograph using chemical reaction interface-mass spectrometry

We have applied a chemical reaction interface-mass spectrometric (CRIMS) technique to the detection of 14C-labeled phenytoin and its metabolites in urine following separation by capillary gas chromatography. The presence of 14C was followed by monitoring 14CH4 which is produced by the chemical reaction interface from carbon when hydrogen is used as the reactant gas. Chromatograms showing 14C are obtained by measuring 14CH4 at m/z 18.034 with a resolution of 1800. The chemical reaction interface permits symmetrical, narrow chromatographic peaks to be obtained. Detection limits of 6.3 Bq/ml (1.26 Bq on-column which is equivalent to detection of 187 pg) of a diethylated 14C-labeled metabolite was detected at a signal-to-noise ratio of 3. The analysis was determined to be linear and similar detection limits were obtained following analysis of phenytoin-spiked urine or a phenytoin solution. Radiocarbon detection is not completely selective because nitrogen-containing compounds present at greater than 250 ng on-column are detected as NH4+. However, such interferences are infrequently of analytical importance because the capacity limits of CRIMS are 500-1000 ng. Furthermore, these interferences are readily discovered in a NH3 chromatogram which is the precursor of NH4+. After a 3.3-MBq dose, the major metabolites of phenytoin were detected by CRIMS.