Analysis and Toxicological Evaluation of Nicotine Degradants and Impurities in Oral Tobacco Products: A Case Study of Nicotine Pouches

Overview

Journal ACS Omega

Publisher American Chemical Society

Specialty Chemistry

Date 2025 Feb 24

PMID 39989796

Authors

Fadi Aldeek

Karl Wagner

Vanessa Haase

Erica Sublette

Vanessa Lopez

Affiliations

Soon will be listed here.

Abstract

This study provides a comprehensive toxicological evaluation of seven nicotine degradants and impurities (e.g., myosmine, nornicotine, anatabine, anabasine, β-nicotyrine, cotinine, and nicotine-'-oxide) in oral nicotine pouches. United States Pharmacopeia (USP) and European Pharmacopeia (EP) limits, International Conference on Harmonization (ICH) guidance, and available toxicity data were considered during the evaluation. The toxicological weight of evidence supports that the levels of nornicotine, anabasine, β-nicotyrine, cotinine, and nicotine-'-oxide do not pose health risks greater than nicotine and therefore do not increase the health risks of oral tobacco products such as nicotine pouches. However, myosmine and anatabine should be closely monitored against appropriate qualification thresholds due to their potential toxicological concerns. A robust UPLC-MS/MS analytical method was developed and validated for the accurate determination of the seven nicotine degradants and impurities in nicotine pouches. The method was utilized to assess the shelf life stability of nicotine in nicotine pouches over a 12-month period under ICH long-term storage conditions. Anabasine, β-nicotyrine, anatabine, and nornicotine were either not detected or found below the limit of quantitation over the course of the stability study. Myosmine, cotinine, and nicotine-'-oxide were found to be 0.055, 0.015, and 1.32% of the target nicotine level, respectively.

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