# Method for simultaneous determination of three cooling agents in aerosols by GC–MS

**Authors:** Tinghao Chen, Chenfeng Hua, Chengjie Ma, Bin Peng, Pingping Shang, Ge Zhao, Quanping Yan, Fuwei Xie

PMC · DOI: 10.3389/fchem.2025.1699107 · 2025-10-31

## TL;DR

This paper introduces a reliable GC-MS method to measure three cooling agents in aerosols, showing their distribution in gas and particle phases.

## Contribution

A validated GC-MS method for simultaneous quantification of three cooling agents in aerosols is developed and tested.

## Key findings

- The method showed excellent linearity, low detection limits, and high accuracy for quantifying cooling agents.
- Cooling agents were predominantly found in the particle phase due to aerosol condensation.
- Gas-phase proportions of menthol, WS-23, and WS-3 were significantly lower than in the particle phase.

## Abstract

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 (R
2 ≥ 0.9994), with limits of detection (LOD, from 0.137 ng/mL to 0.114 μg/mL), limits of quantification (LOQ, from 0.456 ng/mL to 0.380 μg/mL), relative standard deviations (RSDs, 1.40%–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% to 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.

## Linked entities

- **Proteins:** TRPM8 (transient receptor potential cation channel subfamily M member 8), TRPA1 (transient receptor potential cation channel subfamily A member 1)
- **Chemicals:** menthol (PubChem CID 1254), WS-3 (PubChem CID 62907), WS-23 (PubChem CID 65300), N-ethyl-2-(isopropyl)-5-methylcyclohexanecarboxamide (PubChem CID 62907), 2-Isopropyl-N,2,3-trimethylbutyramide (PubChem CID 65300)

## Full-text entities

- **Chemicals:** 2-Isopropyl-N,2,3-trimethylbutyramide (-), menthol (MESH:D008610)
- **Species:** Nicotiana tabacum (American tobacco, species) [taxon 4097]

## Figures

9 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12616255/full.md

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Source: https://tomesphere.com/paper/PMC12616255