When humans breathe, air enters the lungs leading to an interchange of gases between the blood circulation and the air in the lungs. Thus, it has been questioned whether it could be possible to detect chemicals/drugs present in a person’s blood circulation from this interchange process. This has already been demonstrated for volatile substances such as alcohol and even some other less volatile substances (THC, opioid metabolites, etc. (6)(10)), but has not been confirmed for the listed substances (Table 1) yet. In this study, several common over-the counter (OTC) drugs were administered to a group of volunteer subjects and several exhaled breath fractions were analyzed for these drugs. Exhaled breath condensate (EBC) and exhaled breath aerosols (EBA), together with the saliva fraction were collected over a period of 3-time intervals to determine if the drugs (acetaminophen, naproxen, and ibuprofen) or their potential known metabolites can be detected. The sampling intervals were chosen for each drug based on the average expected detection window from their pharmacokinetic profile (i.e. Drugbank, HMDB, and etc.) in the blood stream following administration. Exhaled breath samples were collected by several different methods: 1) a cooled glass tube that retained condensate volatiles and semi-volatile compounds, and 2) filters, such as N95 mask and C18 filters, that capture aerosols and larger molecules. Processed samples were then analyzed by liquid chromatography mass spectrometry, Quadrupole-Time of Flight (LC-MS/MS, qTOF ). The data obtained was analyzed to identify the drugs detected, their metabolites and determine their concentrations. This study has been done using a selected group of common OTC drugs that would most likely be found in the breath of everyday individuals due to their widespread use. Individual volunteers used a custom-made breath condenser (K-tube) and commercial filters (C18 disks and N95 masks) to collect several breath samples following the OTC drug ingestion. These samples included collections at an initial time 0 (T0) before any dose intake along with two or three time-points at specific time intervals after a dose intake. While filters collected aerosol fractions (EBA) from the direct breath exhalations, the K-tube collected lighter breath fractions, EBC, together with an additional ethanolic rinse fraction of the glass tube to get less polar molecules adhered on the surface walls. All fractions, after a proper sample treatment, were then injected into an LCMS/MS system, where the triple quadrupole – Time of Flight (qTOF) analyzer detects presence of the analytes along with their metabolites through exact mass determination and fragmentation. When no targeted compounds were detected, we evaluated the potential impact of possible interference factors such as dose ingested, individual metabolism, sample collection/preparation technique or limited partitioning of the drugs from blood to breath. The final multi-drug experiment yielded a few promising results. Out of the six compounds tested, two (Phenylephrine HCL and Oxymetazoline HCL) were successfully detected based on mass and retention time. These results indicate a potential for more extensive tests in the future to focus in on the low detection range of these drugs.