Chemical ionization mass spectrometry for rapid assay of drugs in serum.

A rapid procedure has been devised for analyzing anti-epileptic drugs in serum by chemical ionization mass spectrometry. An internal standard, 5-(p-methylphenyl)-5-phenylhydantoin (MPPH), is added to serum diluted in buffer at pH 12. The mixture is washed with diethyl ether to remove neutral lipids, acidified, extracted with chloroform and the chloroform extract evaporated to dryness. The residue is then dissolved in methanol and an aliquot, corresponding to approximately 2% of the original mixture, is deposited in the glass capillary sample cup of the solid probe inlet of the mass spectrometer. The sample is then volatilized by heat into the ion source of the mass spectrometer, where it reacts with ionized methane reagent gas. As the temperature of the probe is increased, quasimolecular ion peaks of the protonated anticonvulsants appear, rise and fall on the oscilloscope tracing, indicating similar but not identical rates of volatilization. We recorded these peaks photographically by opening the shutter of the oscilloscope camera for the entire heating cycle. The concentrations of the anticonvulsants were estimated from the ratio of the height of the peaks of the drug to that of the internal standard on the photograph. The peak-height ratios were proportional to concentration within, above and below the therapeutic range. Other drugs, including barbiturates, carbamazepine, nicotine and caffeine, were readily identified when present. With one solid probe inlet, an assay could be performed every 2 min.