A method for screening key components of heated cigarette aerosol

Abstract

This invention relates to the field of heated cigarette aerosol technology, specifically to a method for screening key components of concern in heated cigarette aerosols. The method comprises the following steps: gas chromatography-mass spectrometry (GC-MS) analysis using polar and non-polar chromatographic columns; screening for compounds with high content and significant differences in the aerosol; and screening for carcinogenic and toxic compounds, high-level predicted toxicity risk substances, and precursors of these substances as key components of concern in cigarette aerosols. By employing both polar and non-polar chromatographic columns, the comprehensiveness of the analytical results for various types of cigarette smoke aerosols is ensured. This invention establishes a screening process for key toxic compounds of concern in heated cigarette aerosols, enabling comprehensive and accurate identification of harmful components in heated cigarette smoke aerosols.

Description

Technical Field

[0001] This invention relates to the field of heated cigarette aerosol detection technology, specifically to a method for screening key components of heated cigarette aerosol. Background Technology

[0002] With the rapid rise of global health awareness, the harms of traditional tobacco have become a public consensus, creating enormous development space and market momentum for new tobacco products. Currently, new tobacco products on the market are mainly divided into several categories, including heated tobacco products (HTPs), e-cigarettes, and oral tobacco products. Among them, HTPs are considered the most promising alternative to traditional cigarettes in terms of market share and future potential, due to their ability to provide a taste close to that of traditional cigarettes and their strong promotion by traditional tobacco giants. However, we must be clearly aware that because HTPs release smoke through heating (below 400℃) rather than combustion, and due to their unique chemical composition (HTP core materials contain large amounts of propylene glycol, glycerol, additives, etc.), the composition of HTP aerosols differs from traditional cigarette smoke in terms of the number and content of compounds. Therefore, their long-term health risks still require close attention.

[0003] Chinese patent application CN119165082A, published on December 20, 2024, discloses a method for detecting antioxidants in heated cigarette aerosols. The method involves using a filter to capture aerosols in heated cigarette smoke, then using an extractant to extract the captured aerosols by shaking, obtaining a test solution. The test solution is then analyzed by gas chromatography-mass spectrometry (GC-MS), and the antioxidant content in the aerosol is calculated based on a standard curve method. The GC uses a 35% phenylmethyl polysiloxane inert column. Accurate determination of the release of phenolic antioxidants in heated cigarette aerosols is of great significance for studying the atomization efficiency of heated cigarette additives and the impact of heated cigarettes on smokers' health.

[0004] However, other harmful components cannot be identified or monitored. Therefore, identifying and focusing on the harmful components and their precursors in these aerosols, and screening out components of key concern, has become a crucial and urgent task in the field of public health research and regulation. Summary of the Invention

[0005] The purpose of this invention is to provide a method for screening key components of concern in heated cigarette aerosols, thereby solving the problem that existing technologies cannot identify harmful components and their precursors in heated cigarette aerosols.

[0006] To solve the above-mentioned technical problems, the technical solution of the method for screening key components of heated cigarette aerosol of the present invention is as follows:

[0007] A method for screening key components of interest in heated cigarette aerosol includes the following steps:

[0008] 1) Gas chromatography-mass spectrometry (GC-MS) was used to detect and analyze the aerosols from heated and unheated cigarettes, with both polar and non-polar chromatographic columns employed in the GC-MS analysis.

[0009] 2) Compare the aerosol composition of heated and unheated cigarette smoke and screen out compounds with high content and significant differences in heated cigarette smoke aerosol;

[0010] 3) Among the compounds obtained in step 2), compounds that are permitted to be added to food or are contained in edible plants are excluded. Among the remaining compounds, carcinogenic and toxic compounds, non-carcinogenic and toxic compounds, high-level predicted toxicity risk substances obtained according to Cramer decision, and precursors of these two types of substances are identified as key components of concern in flue gas aerosols.

[0011] This invention provides a pioneering method for screening key components of concern in heated cigarette aerosols. By employing both polar and non-polar chromatographic columns, the comprehensiveness of analytical results for various types of cigarette smoke aerosols is ensured. Compounds with high content and significant differences in heated cigarette smoke aerosols are screened, enabling a comprehensive screening of components requiring key attention. By excluding permitted additives and inherent components from natural edible plants, carcinogenic and toxic compounds and their precursors are screened. Based on Cramer's decision method, high-level predicted toxicity risk substances are identified as key components of concern in smoke aerosols, thus establishing a screening process for key toxic compounds of concern in heated cigarette aerosols. The experimental conclusions obtained from the entire screening scheme and process are accurate and comprehensive.

[0012] Preferably, in step 1), the gas chromatography-mass spectrometry detection and analysis is GC-Orbitrap-MS detection and analysis; the chromatographic columns used in GC-Orbitrap-MS detection and analysis are DB-Wax polar chromatographic columns and DB-5MS non-polar chromatographic columns; the screening conditions when using DB-Wax columns are: TS≥90, HRF≥90, RHRF≥90, SI≥730, RSI≥750, ΔRI≤15; the screening conditions when using DB-5MS columns are: TS≥90, HRF≥90, RHRF≥90, SI≥710, RSI≥710, ΔRI≤15. By selecting thresholds, the probability of false positive results is reduced, and the screening efficiency of unknowns is improved.

[0013] Preferably, in step 2), compounds with high content and significant differences in heated cigarette smoke aerosol are screened according to log2 FC > 0.32 and t test; FC is the semi-quantitative ratio of smoke aerosol components of heated and non-heated cigarettes, and P < 0.05 in t test.

[0014] Preferably, in step 3), the carcinogenic and toxic compounds are carcinogenic, genotoxic, and target organ toxic compounds; target organ toxic compounds include cardiotoxic and pulmonary toxic compounds. Substances with definite carcinogenicity, genotoxicity, and target organ toxicity, including cardiotoxicity and pulmonary toxicity, can be screened and retrieved from the IARC and ECHA databases.

[0015] Preferably, in GC-Orbitrap-MS detection and analysis, when using a DB-Wax polar column, the injection port temperature is 230~240 ℃; the temperature program is: 40~50℃ held for 1 min, then increased to 220~230℃ at a rate of 3~4℃ / min and held for 20 min; the injection mode is splitless injection; the carrier gas is helium, in constant flow mode, with a flow rate of 1~2 mL / min; and the injection volume is 1~2 μL.

[0016] Preferably, the ionization mode for mass spectrometry analysis is: electron ionization; ionization energy: 70 eV; filament current: 50 μA; EI ion source temperature: 230 ℃; transfer line temperature: 230 ℃; collision gas: nitrogen; maximum target capacity: 1×10⁻⁶. 6 Maximum injection time: 200 ms; Quality accuracy: 5×10 -6 Solvent delay: 8.2 min; Acquisition mode: full scan; Quality scan range: 40~500; Quality resolution: 60,000 HW.

[0017] Preferably, in GC-Orbitrap-MS detection and analysis, when using a DB-5MS nonpolar column, the injection port temperature is 290~300 ℃; the temperature program is: 40~50℃ held for 1 min, then increased to 300~310℃ at a rate of 4~5℃ / min and held for 20 min; the injection mode is splitless injection; the carrier gas is helium, in constant flow mode, with a flow rate of 1~2 mL / min; and the injection volume is 1~2 μL.

[0018] Preferably, the ionization mode for mass spectrometry analysis is: electron ionization; ionization energy: 70 eV; filament current: 50 μA; EI ion source temperature: 290 ℃; transfer line temperature: 290 ℃; collision gas: nitrogen; maximum target capacity: 1×10⁻⁶. 6 Maximum injection time: 200 ms; Quality accuracy: 5×10 -6 Solvent delay: 7.2 min; Acquisition mode: full scan; Quality scan range: 40~500; Quality resolution: 60,000 half-width at half-maximum.

[0019] Preferably, in step 1), the method for preparing the test liquid of smoke aerosol from heated and non-heated cigarettes includes the following steps: after smoking heated and non-heated cigarettes, particulate matter and gaseous matter are captured using a capturing material, the capturing material is mixed with the extract and internal standard solution and then extracted, and the test liquid is obtained by filtration.

[0020] Preferably, the extraction is ultrasonic extraction, the ultrasonic extraction temperature is room temperature, the ultrasonic extraction power is 40~60W, and the time is 10~15min; for every three heated or unheated cigarettes smoked, 10~20mL of extract and 100μL of internal standard solution are added; the extract is dichloromethane; the internal standard solution includes 1.2~1.5μg / mL acetophenone-d8 and 1.2~1.5μg / mL diisobutyl phthalate-d4. Attached Figure Description

[0021] Figure 1 This is a flowchart of the screening method for key components of heated cigarette aerosol in Embodiment 1 of the present invention. Detailed Implementation

[0022] The technical concept of the method for screening key components of heated cigarette aerosol provided by this invention is as follows:

[0023] Existing technologies only use gas chromatography-mass spectrometry to detect and analyze antioxidants in heated cigarette smoke aerosols. However, the smoke release mechanism of heated tobacco products (HTPs) is due to heating rather than combustion, resulting in different compound quantities and contents in the aerosols compared to traditional cigarette smoke. It is necessary to identify and focus on the harmful components and their precursors in these aerosols.

[0024] This invention employs both polar and non-polar chromatographic columns for analysis, ensuring the comprehensiveness of analytical results for various types of cigarette smoke aerosols. It also screens carcinogenic and toxic compounds and their precursors, and identifies high-level predicted toxicity risk substances as key components of concern in smoke aerosols based on Cramer decision criteria. This invention establishes a screening process for key toxic compounds of concern in heated cigarette smoke aerosols, enabling comprehensive and accurate identification of harmful components in heated cigarette smoke aerosols.

[0025] The method for screening key components of heated cigarette aerosol provided by this invention includes the following steps:

[0026] 1) After smoking heated and unheated cigarettes, particulate matter and gaseous matter are captured using a capturing material. The capturing material, extract, and internal standard solution are mixed and extracted, and then filtered to obtain the test solution. The test solution is then analyzed by GC-Orbitrap-MS.

[0027] In step 1), the trapping materials include a filter and an XAD-7 adsorption tube; a Cambridge filter is used to trap particulate matter, and an XAD-7 adsorption tube is connected after the trap to trap gaseous matter.

[0028] In step 1), the extraction is ultrasonic extraction. The ultrasonic extraction temperature is room temperature, the ultrasonic extraction power is 40~60W, and the time is 10~15min. For every three heated or unheated cigarettes smoked, 10~20mL of extract and 100μL of internal standard solution are added. The extract is dichloromethane. The internal standard solution includes 1.2~1.5μg / mL acetophenone-d8 and 1.2~1.5μg / mL diisobutyl phthalate-d4.

[0029] In step 1), the aspiration is performed in HCl aspiration mode, with aspiration volume / frequency / duration of 55~60mL / 30~35s / 2~5s respectively.

[0030] In step 1), when using a DB-Wax polar column for chromatographic analysis, the injection port temperature is 230–240 °C; the temperature program is: 40–50 °C for 1 min, then increased to 220–230 °C at a rate of 3–4 °C / min and held for 20 min; the injection mode is splitless injection; the carrier gas is helium, in constant flow mode, with a flow rate of 1–2 mL / min; the injection volume is 1–2 μL. For mass spectrometry analysis, the ionization mode is electron ionization; the ionization energy is 70 eV; the filament current is 50 μA; the EI ion source temperature is 230 °C; the transfer line temperature is 230 °C; the collision gas is nitrogen; and the maximum target capacity is 1 × 10⁻⁶. 6 Maximum injection time: 200 ms; Quality accuracy: 5×10 -6 Solvent delay: 8.2 min; Acquisition mode: full scan; Quality scan range: 40~500; Quality resolution: 60,000 HW.

[0031] In step 1), when using a DB-5MS nonpolar column for chromatographic analysis, the injection port temperature is 290–300 °C; the temperature program is: 40–50 °C for 1 min, then increased to 300–310 °C at a rate of 4–5 °C / min and held for 20 min; the injection mode is splitless injection; the carrier gas is helium, in constant flow mode, with a flow rate of 1–2 mL / min; the injection volume is 1–2 μL. For mass spectrometry analysis, the ionization mode is electron ionization; the ionization energy is 70 eV; the filament current is 50 μA; the EI ion source temperature is 290 °C; the transfer line temperature is 290 °C; the collision gas is nitrogen; and the maximum target capacity is 1 × 10⁻⁶. 6 Maximum injection time: 200 ms; Quality accuracy: 5×10 -6Solvent delay: 7.2 min; Acquisition mode: full scan; Quality scan range: 40~500; Quality resolution: 60,000 half-width at half-maximum.

[0032] In step 1), the screening conditions for the DB-Wax column are: TS≥90, HRF≥90, RHRF≥90, SI≥730, RSI≥750, ΔRI≤15; the screening conditions for the DB-5MS column are: TS≥90, HRF≥90, RHRF≥90, SI≥710, RSI≥710, ΔRI≤15.

[0033] 2) By comparing the aerosol composition of heated and unheated cigarette smoke, compounds with high content and significant differences in heated cigarette smoke aerosol were screened according to log2 FC > 0.32 and t test; FC is the semi-quantitative ratio of aerosol composition of heated and unheated cigarette smoke, and P < 0.05 in t test.

[0034] 3) In the compounds obtained in step 2), exclude compounds that are permitted to be added to food or contained in edible plants by querying the database of permitted added compounds; the database of permitted added compounds includes the Joint FAO / WHO Expert Committee on Food Additives, the US FDA, substances permitted by EU regulations, and the FooDB database.

[0035] 4) Based on the toxic compound database, screen out carcinogenic, genotoxic, and target organ toxic compounds from the compounds excluded in step 3); target organ toxic compounds include cardiotoxic and pulmonary toxic compounds; the toxic compound database includes the IARC and ECHA databases.

[0036] 5) For substances that do not possess clear carcinogenicity, genotoxicity, or specific target organ toxicity (cardiotoxicity, pulmonary toxicity), a toxicity risk classification based on Cramer decision tree rules is performed to obtain substances with high-level predicted toxicity risk. Specifically, Toxtree software is used for the predicted toxicity risk classification. Cramer decision tree rules classify substances based on chemical structure: functional groups, molecular weight, solubility, etc. The chemical structure is input, and the predicted toxicity risk level is output.

[0037] 6) Literature review and analysis identified precursors of two categories of substances: compounds with definite carcinogenicity, genotoxicity, and target organ toxicity (cardiotoxicity, pulmonary toxicity), and substances with high predicted toxicity risk. In general, the key compounds of concern in heated cigarette aerosol include: A: Compounds with definite carcinogenicity, genotoxicity, and target organ toxicity (cardiotoxicity, pulmonary toxicity); B: Compounds with a high predicted toxicity risk based on structure-activity relationships; C: Precursors of Category A substances.

[0038] The embodiments of the present invention will be further described below with reference to specific examples. Unless otherwise specified, the chemical reagents involved in the following examples are all commercially available conventional products.

[0039] I. Specific Embodiments of the Method for Screening Key Components of the Heated Cigarette Aerosol of the Present Invention

[0040] Example 1

[0041] The flowchart of the screening method for key components of heated cigarette aerosol in this embodiment is as follows: Figure 1 As shown, the details are as follows:

[0042] (1) Sample pretreatment

[0043] Smoke collection: A linear smoking machine is used to smoke three cigarettes (heated cigarettes or traditional reference cigarettes (4r5f reference cigarettes developed and produced by the Tobacco Research and Health Center of the University of Kentucky) in HCI mode (smoke volume / frequency / duration: 55mL / 30s / 2s)). Particulate matter is collected using a Cambridge filter, and an XAD-7 adsorption tube is connected after the collector to collect gaseous matter.

[0044] Sample extraction: Place the aspirated filter and the adsorbent in the adsorption tube into an Erlenmeyer flask, add 10 mL of dichloromethane, add 100 μL of internal standard (the mass concentrations of acetophenone-d8 and diisobutyl phthalate-d4 are both 1.2 μg / mL), and sonicate at 40 W for 10 min at room temperature. Let stand for 2 min, and then filter the supernatant through a 0.2 µm filter membrane.

[0045] (2) Instrumental analysis: The samples were analyzed by GC-Obitrap-MS using two chromatographic columns, DB-Wax and DB-5MS.

[0046] Method 1:

[0047] Column: DB-Wax capillary column; Injector temperature: 230 ℃; Temperature program: Injection mode: splitless injection; carrier gas: high-purity helium (99.999%), constant flow mode, flow rate 1 mL / min; injection volume: 1 μL.

[0048] Ionization mode: Electron ionization (EI); Ionization energy: 70 eV; Filament current: 50 μA; EI ion source temperature: 230 ℃; Transmission line temperature: 230 ℃; Collision gas: Nitrogen (99.999%); Maximum target capacity: 1×10 6 Maximum injection time: 200 ms; Quality accuracy: 5×10 -6Solvent delay: 8.2 min; Acquisition mode: Full scan; Mass scan range (m / z): 40~500; Mass resolution: 60000 full width at half maximum (FWHM) (m / z 200).

[0049] Method 2:

[0050] Column: DB-5MS capillary column; Injector temperature: 290 ℃; Temperature program: Injection mode: splitless injection; carrier gas: high-purity helium (99.999%), constant flow mode, flow rate 1 mL / min; injection volume: 1 μL.

[0051] Ionization mode: EI; Ionization energy: 70 eV; Filament current: 50 μA; EI ion source temperature: 290 ℃; Transmission line temperature: 290 ℃; Collision gas: Nitrogen (99.999%); Maximum target capacity: 1×10 6 Maximum injection time: 200ms; Quality accuracy: 5×10 -6 Solvent delay: 7.2 min; Acquisition mode: full scan; Mass scan range (m / z): 40~500; Mass resolution: 60000 FWHM (m / z 200).

[0052] (3) According to the pretreatment conditions, the treated heated tobacco sample solution and the traditional reference cigarette sample solution were mixed at a ratio of 1:1, and 100 μL of mixed standard (containing 27 kinds of alcohols, aldehydes, acids, ketones, esters and heterocyclic compounds, with a concentration of 1 µg / mL, and the specific compound names are shown in Table 1-2) was added to prepare a mixed matrix solution. The mass spectrometry matching and retention index thresholds were obtained by GC-Obitrap-MS analysis.

[0053] Table 1. Types of mixed standard compounds used in DB-WAX threshold screening

[0054]

[0055]

[0056] Table 2. Types of mixed standard compounds for DB-5MS threshold screening

[0057]

[0058]

[0059]

[0060] When using a DB-Wax column, the screening criteria were TS≥90, HRF≥90, RHRF≥90, SI≥730, RSI≥750, and ΔRI≤15. When using a DB-5MS column, the screening criteria were TS≥90, HRF≥90, RHRF≥90, SI≥710, RSI≥710, and ΔRI≤15. By selecting these thresholds, the probability of false positives was reduced, and the screening efficiency for unknowns was improved.

[0061] (4) The data of heated cigarette smoke and conventional cigarette smoke were compared. Data acquisition was performed using TraceFinder™ 5.1 software, and data processing was performed using Compound Discoverer™ 3.3 software. Mass spectra of usable samples with impurities removed were obtained through deconvolution and blank subtraction. The ratio of the semi-quantitative release amounts of heated cigarette smoke and reference cigarette smoke samples was the fold of variation (FC) value. Compounds with high release amounts and significant differences in heated cigarette smoke aerosol were screened according to the conditions of log2 FC > 0.32 and t-test (P < 0.05). A total of 89 substances with release amounts greater than those of conventional reference cigarette smoke were screened. Among them, 57 were analyzed on a DB-5MS column, and 32 were analyzed on a DB-WAX column.

[0062] (5) For compounds with high release levels and significant differences in heated cigarette aerosols, a database search (Joint Expert Committee on Food Additives (JECFA), US FDA, EU regulations on permitted additives, or FooDB database) was conducted to screen for substances that are permitted for addition or are naturally present in edible plants. These substances do not require attention. 66 substances that do not require attention were excluded, as shown in Table 3. Among them, 46 were excluded from the DB-5MS column, and 20 were excluded from the DB-WAX column.

[0063] Table 3. Permitted additives and substances found in natural plants, retrieved from the database.

[0064]

[0065]

[0066]

[0067]

[0068] (6) Substances that are not permitted additives or are not naturally present in edible plants were searched using the IARC and ECHA databases to screen for substances with clear carcinogenicity, genotoxicity, and specific target organ toxicity (cardiotoxicity and pulmonary toxicity). Two components requiring special attention were identified, as shown in Table 4.

[0069] Table 4. Substances with proven carcinogenicity, genotoxicity, or specific target organ toxicity (cardiotoxicity, pulmonary toxicity).

[0070]

[0071] (7) Using Toxtree software, the toxicity risk was predicted and classified based on Cramer decision tree rules for substances that did not have clear carcinogenicity, genotoxicity, or specific target organ toxicity (cardiotoxicity, pulmonary toxicity). Seven substances were identified as having a high predicted risk level (highly monitored), as shown in Table 5. Fourteen substances were identified as having low or medium risk levels (not monitored), as shown in Table 6. 2-Chloro-1,3-propanediol is an isomer of 3-chloro-1,2-propanediol, and the two can interconvert under certain conditions. 2,3-Dihydro-3,5-dihydroxy-6-methyl-4(H)-pyran-4-one is a classic reducing sugar thermal degradation product. The remaining five compounds are acetal or ketal products of glycerol or propylene glycol.

[0072] Table 5. Seven substances classified as high according to Toxtree prediction results.

[0073]

[0074] Table 6. Substances classified as low and medium according to Toxtree prediction results.

[0075]

[0076] (8) Through literature search and analysis, precursors of substances with clear carcinogenicity, genotoxicity, specific target organ toxicity (cardiotoxicity, pulmonary toxicity), and substances with high predicted risk levels were identified, as shown in Table 7 as important precursors and important influencing components. Glycerol and propylene glycol in heated tobacco are smoke-generating agents and important precursors for the formation of glycidol, chloropropanol, or acetal ketals; acetaldehyde, acetone, furfural, and 5-methylfurfural are also important precursors for high-risk acetal ketals; moisture has a significant impact on the formation of these toxic compounds; therefore, glycerol, propylene glycol, moisture, and related aldehydes and ketones such as acetaldehyde, acetone, furfural, and 5-methylfurfural in heated tobacco aerosols are listed as important components of concern. In summary, there are 16 key components of concern in heated tobacco aerosols, as shown in Table 7. Glycerol and propylene glycol are smoke-generating agents, and their formulation and addition amount can be adjusted during the preparation of heated cigarettes.

[0077] Table 7 Key components of concern in heated flue gas aerosols

[0078]

[0079] Finally, it should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for screening key components of heated cigarette aerosol, characterized in that, Includes the following steps: 1) Gas chromatography-mass spectrometry (GC-MS) was used to detect and analyze the aerosols from heated and unheated cigarettes, with both polar and non-polar chromatographic columns employed in the GC-MS analysis. 2) Compare the aerosol composition of heated and unheated cigarette smoke and screen out compounds with high content and significant differences in heated cigarette smoke aerosol; 3) Among the compounds obtained in step 2), compounds that are permitted to be added to food or are contained in edible plants are excluded. Among the remaining compounds, carcinogenic and toxic compounds, non-carcinogenic and toxic compounds, high-level predicted toxicity risk substances obtained according to Cramer decision, and precursors of these two types of substances are identified as key components of concern in flue gas aerosols.

2. The method for screening key components of heated cigarette aerosol as described in claim 1, characterized in that, In step 1), the gas chromatography-mass spectrometry detection and analysis is GC-Orbitrap-MS detection and analysis; the chromatographic columns used in GC-Orbitrap-MS detection and analysis are DB-Wax polar chromatographic columns and DB-5MS non-polar chromatographic columns; the screening conditions when the chromatographic column is DB-Wax are: TS≥90, HRF≥90, RHRF≥90, SI≥730, RSI≥750, ΔRI≤15; the screening conditions when the chromatographic column is DB-5MS are: TS≥90, HRF≥90, RHRF≥90, SI≥710, RSI≥710, ΔRI≤15.

3. The method for screening key components of heated cigarette aerosol as described in claim 1, characterized in that, In step 2), compounds with high content and significant differences in heated cigarette smoke aerosol were screened according to log2 FC > 0.32 and t test; FC is the semi-quantitative ratio of aerosol components in heated and unheated cigarette smoke, with P < 0.05 in the t-test.

4. The method for screening key components of heated cigarette aerosol as described in claim 1, characterized in that, In step 3), carcinogenic and toxic compounds are carcinogenic, genotoxic, and target organ toxic compounds; target organ toxic compounds include cardiotoxic and pulmonary toxic compounds.

5. The method for screening key components of heated cigarette aerosol as described in claim 2, characterized in that, In GC-Orbitrap-MS detection and analysis, when using a DB-Wax polar column, the injection port temperature is 230~240 ℃; the temperature program is: 40~50℃ for 1 min, then increase to 220~230℃ at a rate of 3~4℃ / min and hold for 20 min; the injection mode is splitless injection. Carrier gas: helium, constant flow mode, flow rate 1~2 mL / min; injection volume: 1~2 μL.

6. The method for screening key components of heated cigarette aerosol as described in claim 5, characterized in that, Ionization mode during mass spectrometry analysis: electron ionization; ionization energy: 70 eV; filament current: 50 μA; EI ion source temperature: 230 ℃; transfer line temperature: 230 ℃; collision gas: nitrogen; maximum target capacity: 1×10⁻⁶ 6 Maximum injection time: 200 ms; Quality accuracy: 5×10 -6 ; Solvent delay: 8.2 min; Acquisition mode: full scan; Quality scan range: 40~500; Quality resolution: 60000 half-width at half-maximum.

7. The method for screening key components of heated cigarette aerosol as described in claim 2, characterized in that, In GC-Orbitrap-MS detection and analysis, when using a DB-5MS nonpolar column, the injection port temperature is 290~300 ℃; the temperature program is: 40~50℃ for 1 min, then increase to 300~310℃ at a rate of 4~5℃ / min and hold for 20 min; the injection mode is splitless injection. Carrier gas: helium, constant flow mode, flow rate 1~2 mL / min; injection volume: 1~2 μL.

8. The method for screening key components of heated cigarette aerosol as described in claim 7, characterized in that, Ionization mode during mass spectrometry analysis: electron ionization; ionization energy: 70 eV; filament current: 50 μA; EI ion source temperature: 290 ℃; transfer line temperature: 290 ℃; collision gas: nitrogen. Maximum target capacity: 1×10 6 Maximum injection time: 200 ms; Quality accuracy: 5×10 -6 Solvent delay: 7.2 min; Acquisition mode: full scan; Quality scan range: 40~500; Quality resolution: 60000 half-width.

9. The method for screening key components of heated cigarette aerosol as described in claim 1, characterized in that, In step 1), the method for preparing the test liquid of smoke aerosol from heated and non-heated cigarettes includes the following steps: after smoking heated and non-heated cigarettes, particulate matter and gaseous matter are captured using a capturing material, the capturing material is mixed with the extract and internal standard solution and then extracted, and the test liquid is obtained by filtration.

10. The method for screening key components of heated cigarette aerosol as described in claim 9, characterized in that, The extraction was performed using ultrasonic extraction at room temperature, with a power of 40-60W and a time of 10-15 minutes. For every three heated or unheated cigarettes smoked, 10-20 mL of extract and 100 μL of internal standard solution were added. The extract was dichloromethane. The internal standard solution included 1.2-1.5 μg / mL acetophenone-d8 and 1.2-1.5 μg / mL diisobutyl phthalate-d4.

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