Amphetamine, methamphetamine, MDMA, pseudoephedrine, and ephedrine are measured in blood, serum, and plasma using gas chromatography coupled to mass spectrometry (GC/MS). Following a simple liquid–liquid extraction, analytes are derivatized with heptafluorobutyric anhydride (HFBA) and 1 �L injected onto a HP-5MS 15-meter capillary column. Quantitation of each analyte is accomplished using a multi-point calibration curve and deuterated internal standards. The method provides a simple, robust, and reliable means to identify and measure these analytes.