Determination of eight drugs of abuse in blood has been performed using paper spray or extraction spray mass spectrometry in under 2 min with minimal sample preparation. A method has been optimized for quantification of amphetamine, methamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), morphine, cocaine, and Δ9-tetrahydrocannabinol (THC) from a single blood spot. Sample to sample variations of 1-5% relative standard deviation were achieved using stable isotope-labeled internal standards and tandem mass spectrometry. Limits of detection for all drugs were below typical physiological and toxicological levels. Paper spray and extraction spray each used less than 10 μL of whole blood. These methods exhibit the potential for performing rapid and high-throughput assays for selective on-site multicompound quantitative screening of illicit drugs.