Abstract: Vape, as novel nicotine delivery systems, contain various food-grade or non-food-grade additives in their e-liquids and aerosols. Illicit addition of toxic/harmful substances further endangers consumer health. This review summarizes recent progress in identifying e-cigarette toxicants, sample pretreatment methods, and detection technologies, while outlining future research directions to strengthen regulatory oversight.

Table of Contents

• Introduction
• Classification of Toxic/Harmful Components in Vape
• Physicochemical Properties and Hazards
• Sample Pretreatment Techniques
• Analytical Detection Methods
• Conclusions and Future Perspectives

1. Introduction

Electronic cigarettes (Vape), also termed virtual cigarettes, utilize atomizers to aerosolize chemical constituents from e-liquids, simulating conventional cigarette smoking [1-2]. Recently, illicit actors have added psychoactive substances to e-liquids—marketed under deceptive claims like "enhanced," "more satisfying," or "legal high"—creating illegal production and distribution chains that threaten public health and social order.

This article comprehensively reviews the physicochemical properties, toxicology, and analytical methodologies for toxicants in Vape, aiming to support evidence-based regulation and combat narcotics-related e-cigarette crimes.

2. Classification of Toxic/Harmful Components

Vape are battery-powered devices that heat e-liquids into inhalable aerosols. Primary constituents include nicotine/nicotine salts, humectants (e.g., propylene glycol, glycerol), sweeteners (e.g., sucralose, acesulfame), and flavorants. Toxic components are categorized as:

• Nicotine and its salts
• Phthalate esters
• Phenolic compounds
• Carbonyl compounds
• Heavy metals
• Illicit drug additives

3. Physicochemical Properties and Hazards

3.1 Nicotine and Salts

Nicotine (C₁₀H₁₄N₂), a highly addictive alkaloid, rapidly enters circulation via inhalation, stimulating the central nervous system [6]. China's mandatory standard GB41700-2022 limits nicotine to ≤20 mg/g in e-liquids.

3.2 Phthalate Esters

These plasticizers migrate from packaging materials into e-liquids. As endocrine disruptors, they impair reproductive function.

3.3 Phenolic Compounds

Compounds like phenol, hydroquinone, and bisphenol A irritate respiratory/dermal systems and are carcinogenic. Bisphenol A is a recognized endocrine disruptor.

3.4 Carbonyl Compounds

Eight low-molecular-weight carbonyls (formaldehyde, acetaldehyde, acrolein, etc.) are priority toxicants. Formaldehyde, acetaldehyde, and acrolein are IARC-classified carcinogens. Studies detect formaldehyde and acetaldehyde in 100% of tested e-cigarette aerosols [Goniewicz et al.].

3.5 Heavy Metals

Pb, As, Cr, Hg, Ni, Cd, and Sb leach from metal components (coils, tanks, wiring). Bioaccumulation causes enzyme inhibition and chronic toxicity.

3.6 Illicit Drug Additives

Substances like etomidate, synthetic cannabinoids (SCs), and methamphetamine are covertly added to create "spiked Vape." SCs mimic Δ9-THC effects, while etomidate exploits sedative properties.

4. Sample Pretreatment

Complex matrices and trace analytes necessitate advanced pretreatment:

• High-abundance analytes (e.g., nicotine, phenolics): Direct sampling with liquid-liquid extraction (LLE) or solid-phase extraction (SPE).
• Trace analytes: Enrichment via solid-phase microextraction (SPME), single-drop microextraction (SDME), headspace sorptive extraction (HSSE), or accelerated solvent extraction (ASE). Example: SDME with [C₆MIM][PF₆] ionic liquid achieved 1 ng/L detection for chlorobenzene [Chisvert et al.].

5. Analytical Detection Methods

5.1 Spectroscopic Techniques

• Advantages: Rapid, non-destructive, minimal sample prep (e.g., SERS for nicotine [Chien et al.]).
• Limitations: Lower sensitivity, high purity requirements.

5.2 Chromatographic-Mass Spectrometric Techniques

Advantages: High sensitivity, resolution, and multi-analyte capability.

Limitations: Costly instrumentation, complex sample prep.

• GC-MS: Phthalates, SCs, etomidate [LOD: 0.04–0.28 mg/kg].
• LC-MS/MS: Phenolics, nicotine, SCs [LOD: 0.07 pg/mL for nicotine].
• ICP-MS: Heavy metals [LOD: 0.3–667 ng/m³].

Table 1: Nicotine Detection Methods

Table 2: Synthetic Cannabinoid (SC) Detection