Plant-Derived and Synthetic Nicotine in E-Cigarettes: Is Differentiation with NMR Spectroscopy Possible?

Area of Science:

• Analytical Chemistry
• Spectroscopy
• Forensic Science

Background:

• Producers increasingly use synthetic nicotine (tobacco-free nicotine, TFN) in e-cigarettes to bypass regulations, necessitating methods to differentiate it from plant-derived nicotine (tobacco-derived nicotine, TDN).
• Distinguishing between TDN and TFN is challenging due to the cost of synthetic nicotine enantiomeric purification and the need for precise analytical tools.

Purpose of the Study:

• To develop and validate analytical methods capable of distinguishing the origin of nicotine (TDN vs. TFN) in e-cigarette products.
• To establish cost-effective spectroscopic techniques for identifying enantiomeric purity and source of nicotine in e-liquids.

Main Methods:

• Optimization of low-field (LF) ¹H NMR spectroscopy using (R)-(-)-1,1'-binaphthyl-2,2'-diyl hydrogen phosphate (BNPPA) as a chiral complexing agent to assess enantiomeric purity.
• Validation of a direct ¹³C NMR method at natural abundance for differentiating (S)-TDN and (S)-TFN based on relative carbon content.
• Application of Principal Component Analysis (PCA) to analyze spectroscopic data from 12 commercial e-cigarette products.

Main Results:

• The LF ¹H NMR method successfully determined enantiomeric purity, with a limit of quantification of 8 mg/mL nicotine, indicating most products contained a single isomer (likely (S)-(-)-nicotine).
• The validated ¹³C NMR method demonstrated high precision (<0.2% intraday and interday) for distinguishing (S)-TDN from (S)-TFN.
• PCA effectively visualized differences between e-cigarette products based on their nicotine source, confirming the utility of the developed methods.

Conclusions:

• LF ¹H NMR is a viable, cost-effective alternative to high-field NMR for differentiating racemic mixtures from single optical isomers.
• High-precision ¹³C NMR is essential for accurately distinguishing between (S)-TDN and (S)-TFN in e-cigarette samples post-extraction.
• The developed analytical strategies provide crucial tools for verifying nicotine sourcing in e-cigarettes, supporting regulatory oversight and consumer safety.