As submitted by the proposer: Current technology does not meet the need for rapid, effective, and simple drug screening methodologies in forensic toxicology. This project proposes to develop a relatively new analytical technology called paper spray mass spectrometer into an effective tool for drug screening of postmortem blood samples and other forensically relevant specimens. In this method, drug detection by mass spectrometry is carried out directly from a blood sample deposited on paper. It requires no sample preparation and can detect drugs and drug metabolites at forensically relevant levels directly from biofluid matrices. Other distinguishing characteristics of this technique include its speed, simplicity, lower cost, and the low blood sample volume consumed (around 10 uL). This project will evaluate and improve the capabilities of this method for the rapid detection of 154 forensically important drug and drug metabolite targets for use as a drug screening method in toxicology. Validation will be done in collaboration with AIT Laboratories, a national toxicology laboratory specializing in forensic toxicology, compliance monitoring, and clinical testing. Archived postmortem blood samples obtained from AIT will be analyzed by both paper spray MS and the screening program in place at AIT Labs. The two approaches will be evaluated against GC- or LC-MS confirmatory tests. In addition to developing and validating a paper spray MS method for drug screening in blood, this study will also perform proof-of-concept studies in other forensically important matrices such as liver tissue, bile, and urine. The outcome of this project will be an optimized paper spray mass spectrometry method for the rapid screening of forensically relevant drugs in blood samples and other matrices. The validation data, the evaluation results against currently accepted screening methods, and protocols sufficient detail reproduce the data will be reported and archived.