A RAPID NOVEL DERIVATIZATION OF AMPHETAMINE AND METHAMPHETAMINE USING2,2,2-TRICHLOROETHYL CHLOROFORMATE FOR GAS-CHROMATOGRAPHY ELECTRON IONIZATION AND CHEMICAL-IONIZATION MASS-SPECTROMETRIC ANALYSIS

Amphetamine and methamphetamine are commonly abused central nervous sy stem stimulants. We describe a rapid new derivatization of amphetamine and methamphetamine using 2,2,2-trichloroethyl chloroformate for gas chromatography-mass spectrometric analysis. Amphetamine and methamphet amine, along with N-propyl amphetamine (internal standard), were extra cted from urine using 1-chlorobutane. The derivatization with 2,2,2-tr ichloroethyl chloroformate can be achieved at room temperature in 10 m inutes. The electron ionization mass spectrum of amphetamine 2,2,2-tri chloroethyl carbamate showed two weak molecular ions at m/z 309 and 31 1, but showed diagnostic strong peaks at m/z 218, 220, and 222. In con trast, chemical ionization of the mass spectrum of amphetamine 2,2,2-t richloroethyl carbamate showed strong (M + 1) ions at m/z 310 and 312 and other strong diagnostic peaks at m/z 274 and 276. The major advant ages of this derivative are the presence of a diagnostic cluster of pe aks due to the isotopic effect of three chlorine atoms (isotopes 35 an d 37) in the derivatized molecule and the relative ease of its prepara tion. We also observed strong molecular ions for derivatized methamphe tamine in the chemical ionization mass spectrum, but the molecular ion s were very weak in the electron ionization mass spectrum. We used the scan mode of mass spectrometry in all analyses. When using a urine st andard containing 1,000 ng/ml of amphetamine (a 7.4-mu mol/L concentra tion) and methamphetamine (a 6.7-mu mol/L concentration), the within-r un precisions were 4.8% for amphetamine and 3.6% for methamphetamine. The corresponding between-run precisions were 5.3% for amphetamine and 6.7% for methamphetamine. The assay was linear for amphetamine and me thamphetamine concentrations of 250 to 5,000 ng/mL (amphetamine, 1.9-3 7.0 mu mol/L; methamphetamine, 1.7-33.6 mu mol/L). The detection limit was 100 ng/mL (amphetamine, 0.74 mu mol/L; methamphetamine, 0.67 mu m ol/L) using the scan mode of electron ionization mass spectrometry. We observed good a correlation between the concentrations of amphetamine and methamphetamine in five urine specimens positive for amphetamines using the more conventional pentafluoropropionyl derivative and our n ew derivative using 2,2,2-trichloroethyl chloroformate.