Automated sample preparation enables highly reproducible quantitative analyses while meeting the increased efficiency needs often required for sample processing in laboratories. This application note describes results obtained using a liquid handling-based automation system for the sample preparation of compounds to be analyzed by LC-MS/MS and applied to the monitoring of multiple classes of pharmaceutical and illicit drugs. This screen panel contains 56 compounds that could be identified and quantified over a wide range of concentrations from 0.5X to 10X the cut-off value. In addition, the large majority of the compounds could be analyzed with accuracy over 80% and CV under 15%. This method provides automated capabilities for analytical laboratories that currently routinely process samples manually for the monitoring of these drugs in biological fluids.