Abstract: A rapid and simple gas chromatography–mass spectrometry (GC–MS) method was developed and validated for the simultaneous detection and quantification of five psychotropic phenylalkylamines (amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, and norketamine) in toenails. After external decontamination, nail clippings were mechanically pulverized with a bead mill and then incubated in methanol under ultrasonication at 50°C for 1 h. The resulting solutions were evaporated to dryness, derivatized, and analyzed by GC–MS. The intra- and inter-day precisions were within 10.7% and 13.9%, respectively. The intra- and inter-day accuracies were −4.2% to 5.0% and −2.4% to 8.4%, respectively. Limits of detection and quantification for each analyte were lower than 0.024 and 0.08 ng/mg, respectively. The recoveries were in the range of 80.6–87.5%. The results indicated that the proposed method is a simple, rapid, accurate, and precise for quantification of five phenylalkylamines in nails. The method was successfully applied to the simultaneous detection and quantification of phenylalkylamines in nail samples of possible drug abusers.