A dilute and shoot method for simultaneous determination of nicotine and related impurities in e-liquid formulations by UPLC-UV-MS has been developed for routine QC testing of e-cigarette formulations. Due to the differences in the concentration of nicotine (mg level) and related impurities (µg level) in e-liquids, two separate analyses are typically performed for nicotine using GC-FID or LC-UV and for impurities using GC-MS or LC-MS/MS.

E-liquid manufacturing and nicotine purity standards are currently being established worldwide. As nicotine used in e-liquids is extracted from tobacco, the extracted nicotine contains varying amounts of related alkaloid impurities. The concentration of nicotine and related impurities in e-liquids and e-cigarettes is known to change during the product shelf-life as nicotine degrades or gets oxidized to nicotine-n-oxide. The American E-liquid Manufacturing Standards Association (AEMSA) recommends using USP or certified nicotine with purity greater than or equal to 99%, with nicotine-n-oxide less than or equal to 1% and total contaminants less than or equal to 1%.

Simultaneous determination of nicotine and related impurities in e-liquids was achieved using a seven minute UPLC method and two detectors (UV and MS). A wide linear dynamic range for nicotine (2.5-500 µg/mL) using PDA detector and for related impurities (0.005-0.5 µg/mL) using MS detector was used. Six different commercially available e-liquids and e-cigarette cartridges were analyzed. E-liquid samples were diluted 100-fold before analysis, eliminating the need for multiple methods.

The measured nicotine levels in e-liquids were observed to be within 15% of labeled claims. The levels of impurities in e-liquids ranged from not detected to 2.79% of nicotine concentration. Single quadrupole MS detection can be incorporated into existing LC workflows to provide orthogonal detection to UV detectors for simultaneous analysis of nicotine and related impurities on a single instrument platform in a single injection.