Leachables are substances that have the potential to transfer to a product from its container closure system. For Electronic Nicotine Delivery Systems (ENDS), leachables may transfer from all materials that contact the e-liquid. Leachable substances from materials in contact with e-liquid may subsequently transfer to the aerosol and be inhaled by the user. There is no specific guidance for conducting leachable studies on ENDS, there is general guidance for inhaled drug products (United States Pharmacopeia, Chapters 1663 & 1664; ISO-10993-18, Product Quality Research Institute - Best Practices for Extractables and Leachables in Orally Inhaled and Nasal Drug Products, etc.). Herein, we present a workflow for the analysis of leachable compounds in ENDS. To illustrate the workflow’s applicability, we present a case study using the JUUL2 pod-based ENDS system. First, leachable compounds were assessed for closed JUUL2 pods filled with non-commercial base e-liquid formulation (propylene glycol/glycerin/nicotine/benzoic acid). Results for the initial analyses performed using GC-MS and LC-MS (+/- mode) provided a list of 29 organic compounds including potential leachables and nicotine related compounds. After long-term 12-month ambient storage of JUUL2 pods, e-liquid formulation was re-analyzed to investigate the migration of substances over time which provided a list of 12 previously and 24 newly identified compounds. Finally, to better understand potential exposure to leachable compounds, aerosol was collected from the aged pods using non-intense and intense puffing. Results indicated 11/18 of the organic compounds identified in the GC-MS analysis of the e-liquid transferred to aerosol while only 5/30 of the organic compounds identified in the LC-MS analysis transferred. Under GC/MS evaluation, non-nicotine related compounds transferred to aerosol, whereas LC/MS aerosol transfer was exclusively nicotine related compounds. This work supports the observation that larger compounds have limited transfer efficiencies into the aerosol.