GC-MS determination of nicotine in heterogeneous tobacco-free products: ISO/IEC 17025 validation and adaptation of CORESTA RM No. 62.

The rapid diversification of tobacco-free nicotine products has introduced chemically heterogeneous carrier matrices, including cellulose-based materials, herbal systems, and polymer-bound formulations such as nicotine polacrilex, which can significantly affect nicotine extraction and quantification. In this study, a gas chromatography-mass spectrometry (GC-MS) method based on CORESTA Recommended Method No. 62 was adapted and validated for the determination of nicotine in tobacco-free products. Validation was performed using both matrix-matched samples (nicotine sticks) and procedural blank solutions (nicotine pouches), reflecting the analytical challenges associated with heterogeneous matrices. The method showed excellent linearity (r > 0.999), recoveries of 87-94% and 80-111% for sticks and pouches, respectively, precision below 10% RSD, and limits of quantification of 0.035-0.038 mg g-1. Expanded measurement uncertainty was estimated at approximately 9-10% (k = 2). The method was successfully applied to commercial nicotine pouches and nicotine sticks, revealing substantial discrepancies between declared and measured nicotine contents, largely attributable to product variability rather than analytical limitations. A nicotine polacrilex-containing formulation was evaluated under multiple extraction conditions, demonstrating that standard alkaline extraction enables efficient release of polymer-bound nicotine without the need for more aggressive treatments. The proposed approach provides a robust and transferable analytical framework for nicotine determination in chemically diverse tobacco-free matrices, supporting both product characterisation and regulatory assessment.