There is significant regulatory and economic need to distinguish between tobacco-derived (TDN) and synthetic (SynNic) in commercial products. While products that contain TDN are regulated by FDA, those with SynNic are currently exempt from regulatory authority, a grey area that provides a loophole for SynNic commercialization without the quality and safety checks that go along with a PMTA. Furthermore, SynNic is frequently racemic, containing 50% of the poorly characterized (R) enantiomer of nicotine, creating the possibility of unpredictable nicotine responses in users. There is little to no toxicological or physiological data for the (R) enantiomer and there are no published studies which differentiate between TDN and SynNic in commercial e-liquids or nicotine pouches.

TDN is typically comprised of ~99.3% (S)-nicotine enantiomer; while SynNic from traditional syntheses is racemic (i.e., 50/50 (R)-nicotine and (S)-nicotine enantiomers). SynNic can be purified through chiral resolution or separation to obtain >99% S nicotine, but at a yield loss of at least fifty percent. Technical challenges of SynNic purification can be prohibitively expensive resulting in shortcuts and variable quality.

Here we provide data on the enantiomeric purity, levels of nicotine degradants, metals, and TSNAs from several synthetic and tobacco derived sources of nicotine used in the manufacturer of nicotine containing e-liquids and discuss technical limitations.