Electronic Nicotine Delivery System (ENDS) e-liquids typically comprise the main components; nicotine, propylene glycol, glycerine, and flavouring compounds. US Pharmacopeia (USP) grade nicotine is commonly used during the formulation of these ENDS e-liquids, and USP-grade nicotine requires single impurities to be less than 0.5% and total impurities to be less than 1%. Known impurities of nicotine include the nicotine degradants, nornicotine, myosmine, cotinine, anatabine, anabasine, nicotine-n-oxide, and β-nicotyrine, and the tobacco specific nitrosamines (TSNAs) NNN and NNK. Together, these TSNA impurities and nicotine degradants include carcinogenic and respiratory irritants reportable to the FDA under Section 904(a)(3) of the Federal Food, Drug, and Cosmetic Act. Published methods used for quantitation of these sets of compounds include either GC/MS or LC/MS and separate the quantitation of TSNAs and nicotine degradants. Utilizing LC-MS/MS instrumentation in multiple reaction monitoring (MRM) mode with the Acquity UPLC trifunctionally bonded BEH C18 column, a combined analysis method was developed and utilized for the quantitation of TSNA impurities and nicotine degradants in e-liquids and trapped ENDS aerosol. Electrospray ionization (ESI) using a low fragmentation voltage of 50V, focusing all detection through the MRM mode, allowed for an instrument analysis range of ~30-3000 ng/mL for all nicotine degradants and ~0.2-100 ng/mL for TSNAs. Retention time of all compounds fall between 2.5-9 min in a total 14-minute single injection, creating an overall savings of analysis time. This combined analysis method for TSNAs and nicotine degradants shows a detection range equivalent to that of published methodologies with the added benefit of increased throughput, waste reduction, reduced sample collection time and direct data correlation of related nicotine constituents.