LC/MS systems have made a significant impact on sample preparation requirements in forensic toxicology. In particular, highly sensitive LC/MS triple quadrupole instruments allow for low volumes of sample solutions, even when trying to achieve very low detection limits. In addition, the efficiency in HPLC separations minimizes the need for rigorous extraction processes to purify samples for analysis. In this presentation, we demonstrate an improved automated protein precipitation method1 that provides rapid and sensitive analyses of comprehensive drugs and metabolites in whole blood. The method uses an automated protein precipitation procedure with Tip-on-Tip (ToT) filtration to provide robust sample preparation while minimizing opportunity for human error. By using a very sensitive LC/MS system, we show a quick, low cost sample preparation procedure for accurately and reproducibly quantitating drugs and metabolites in whole blood.