Quantitative measurement of amphetamine in human plasma by gas chromatography/negative ion chemical ionization mass...

A selected ion monitoring stable isotope dilution gas chromatographic/negative ion chemical ionization mass spectrometric assay for amphetamine in human plasma is described. The preparation of (2H5)amphetamine from the intact target molecule and its use as an internal standard for quantitative gas chromatography/mass spectrometry are demonstrated. Derivatization to the highly electrophoric pentafluorobenzoate with pentafluorobenzoyl chloride in hexane resulted in high yield of prominent negative ions with methane as a moderating gas. The pentafluorobenzoate was also found to be superior to fluoroacyl derivatives with respect to sample handling due to its lower volatility. The method presented permits detection of amphetamine in the low picogram per millilitre range and should thus be highly useful for its trace level determination in forensic, toxicological and pharmaceutical applications.