Synthetic Nicotine

Synthetic nicotine, which is man-made and not extracted from the tobacco plant, has gained popularity in the past few years.


Tobacco-derived nicotine contains predominantly (S)-Nicotine (~99.3%) and less than 1% (R)-Nicotine, with a small amount of (R)-Nicotine formed during combustion. Tobacco-derived nicotine is regulated under the FDA Center for Tobacco Products and has the CAS# 54-11-5.

Chiral Chromatography
Synthetic nicotine on the other hand does not come from the tobacco plant. It is synthesized using either a chemical or an enzymatic process. This is then often followed by a chemical or enantiomeric purification. There are multiple forms of synthetic nicotine. Synthetic nicotine can be identical to tobacco derived nicotine and be >99% (S)-nicotine, or can be a racemic mix of (R)- and (S)- (50/50 with the CAS # 22083-74-5) or vary in the ratios of (R)- and (S)-nicotine.

Enthalpy has developed its own method to detect the ratios of S and R nicotine in synthetic nicotine products using chiral chromatography. This method uses a chiral stationary phase to separate and measure the relative amounts of the two nicotine stereoisomers (R)- and (S)-nicotine. While this method can be used to identify racemic synthetic nicotine, it cannot differentiate synthetic that is >99% (S)-nicotine since tobacco-derived nicotine contains >99% (S)-nicotine.

Radiocarbon Analysis
Enthalpy also offers radiocarbon analysis for clients who want to test to see if their nicotine is synthetic or tobacco derived. The radiocarbon method ASTM D6866 involves measuring the percentage of carbon from natural (plant or biobased) sources versus synthetic (petrochemical or fossil) sources. The percentage of Carbon-14 (C14), a naturally occurring isotope of carbon, can be used to distinguish synthetic nicotine from tobacco-derived nicotine (TDN contains 100% of the natural ambient C14 and Synthetic nicotine contains 36-38% C14).

Testing Details

In addition to synthetic determination testing Enthalpy also offers HPHC testing on synthetic nicotine products. In March of 2022 synthetic nicotine became the subject of new regulations from the FDA. The FDA now requires a PMTA submission for any nicotine products using synthetic nicotine in place of tobacco derived nicotine. Enthalpy has the ability to test synthetic nicotine products in the very same way we test tobacco derived nicotine products for all FDA recommended HPHCs.