Method for Simultaneous Determination of Three Cooling Agents in Aerosols by GC–MS

Tinghao ChenQuanping Yan^*Fuwei Xie^*Chenfeng HuaChengjie MaBin PengPingping ShangGe Zhao

• China National Tobacco Corp Zhengzhou Tobacco Research Institute, Zhengzhou, China

A cooling sensation is primarily elicited by cooling agents through activation of cold-sensitive receptors such as TRPM8 and TRPA1. Coolants are widely used as functional additives in various industries including food, personal care, pharmaceuticals, and tobacco. In this study, a gas chromatography–mass spectrometry (GC-MS) method was developed to quantify three representative cooling agents—menthol, WS-3(N-ethyl-2-(isopropyl)-5-methylcyclohexanecarboxamide), and WS-23(2-Isopropyl-N,2,3-trimethylbutyramide)—in aerosol samples. The test aerosols were generated from laboratory-formulated e-liquids under optimized conditions. Aerosols were obtained from an electronic vaping device manufactured by RELX (China).The results demonstrated that: (1) the analytical method exhibited good linearity(R2≥ 0.9994), with limits of detection(LOD, from 0.137 ng/ml to 0.114μg/ml), limits of quantification(LOQ, from 0.456 ng/ml to 0.380 μg/ml), relative standard deviations(RSDs, 1.40% to 4.15%), and spiked recovery rates(from 91.32% to 113.25%) all meeting the requirements of analytical validation; (2) the cooling agents were detected in both gas and particle phases of the aerosol, with the concentrations in gas-phase being significantly lower than those in the particle phase due to aerosols condensation. Specifically, the gas-phase proportions of menthol, WS-23 and WS-3 ranged from 1.94–5.72%, 0.03–0.08%, and 0.10–0.18%, respectively. Therefore, the developed GC-MS method satisfies methodological validation criteria and is suitable for application to commercial aerosol samples. It provides a reliable analytical foundation for studying sensory perception of cooling agents under aerosol exposure and offers more precise guidance for their use.