An end-to-end quantitative migration and conversion analysis method for chemical components of a heat-not-burn tobacco product and application thereof

Abstract

The present application belongs to the technical field of tobacco chemical analysis, and particularly relates to an end-to-end quantitative migration and conversion analysis method for chemical components of a heat-not-burn tobacco product and application. The present application establishes a non-target analysis method based on GC-Orbitrap / MS, which is suitable for analysis of a tobacco core and aerosol of a heat-not-burn cigarette. A plurality of sets of control samples are analyzed by using the established systematic and comparable analysis method. Based on statistical results, attribution analysis is performed on the components of the aerosol of the heat-not-burn cigarette, so as to determine which are pyrolysis components newly generated in the heating process and which are components migrated from the tobacco core to the aerosol, and to realize comprehensive and systematic analysis of the migration and conversion rules of the chemical components of the heat-not-burn cigarette. Based on the analysis results, technical and data support can be provided for production design of the heat-not-burn cigarette.

Description

Technical Field

[0001] This invention belongs to the field of tobacco chemical analysis technology, specifically relating to an end-to-end quantitative migration and transformation analysis method and its application for chemical components in heated non-combustible tobacco products. Background Technology

[0002] Heated cigarettes are a new type of tobacco product that produces smoke through low-temperature distillation of tobacco core sheets under heating without combustion. Due to differences in the composition of the tobacco stick and smoking conditions compared to traditional cigarettes, the pyrolysis and migration patterns of tobacco smoke components in heated cigarettes also differ significantly from those in traditional cigarettes. Understanding these pyrolysis and migration patterns of chemical components is a crucial prerequisite for precise harm reduction (e.g., reducing the content of highly migrating harmful substances), efficacy evaluation (e.g., calculating the delivery efficiency of effective components), and optimization of heating methods.

[0003] Currently, the analysis of chemical transfer and transformation of heated cigarette components focuses on specific targets. For example, Chinese invention patent application CN114002170A, published on February 1, 2022, determined the migration rate of nicotine in heated cigarettes using spectrophotometry. Chinese invention patent application CN109738548A, published on May 10, 2019, discloses a method for determining the puff-by-puff transfer rate of menthol isomers in heated non-combustible cigarettes, which uses gas chromatography-mass spectrometry to determine the puff-by-puff transfer rate of menthol isomers into cigarette smoke.

[0004] The transfer analysis of the aforementioned specific targets cannot comprehensively and systematically resolve the sources of chemical components (intrinsic migration or heating-induced regeneration) of heated cigarette aerosols, thus restricting the design of harm reduction for heated cigarettes based on chemical mechanisms; and the unknown migration rate of effective components cannot provide basic data support for product optimization.

[0005] In addition, heated cigarette tobacco smoke contains thousands of components. While the aforementioned spectrophotometric and conventional gas chromatography-mass spectrometry methods can meet the analytical needs of specific targets, they are insufficient in terms of quality accuracy, detection sensitivity, and detection throughput. They cannot comprehensively and accurately analyze the components of heated cigarette tobacco smoke, resulting in the lack of a method for comprehensive and systematic analysis of the migration and transformation laws of chemical components in heated cigarettes. Summary of the Invention

[0006] The first objective of this invention is to provide an end-to-end quantitative migration and transformation analysis method for chemical components in heated tobacco products, thereby solving the problem that existing technologies cannot systematically analyze the migration and transformation characteristics of chemical components in heated cigarettes.

[0007] The second objective of this invention is to provide an application of the above-mentioned end-to-end quantitative migration and transformation analysis method of chemical components in heated tobacco products in the design of harm reduction and quality improvement of heated cigarettes, thereby solving the problems of blindness and incompleteness in the existing harm reduction and quality improvement design of heated cigarettes.

[0008] To achieve the above objectives, the technical solution adopted by the present invention is as follows:

[0009] An end-to-end quantitative migration and transformation analysis method for chemical components in heat-not-combustible tobacco products includes the following steps:

[0010] (1) Establish a high-resolution mass spectrometry library of tobacco smoke components;

[0011] (2) After grinding the cigarette core into powder, solvent extraction was performed. The compounds in the cigarette core were quantitatively analyzed by non-target relative analysis using GC-Orbitrap / MS, and the content of each component in a single cigarette was recorded. The cigarette core was heated and smoked to collect the aerosol of the heated cigarette smoke. Then, the same solvent extraction and GC-Orbitrap / MS analysis were performed to record the release amount of each component in the aerosol of each cigarette.

[0012] (3) Statistical analysis was performed on multiple groups of heated cigarette cores and corresponding smoke aerosol components to identify newly generated pyrolysis components and migrating components: substances that were quantitatively detected in the smoke of all grouped samples but not detected in the cigarette core, or substances whose smoke aerosol release was higher than that of the cigarette core, were classified as newly generated pyrolysis components; substances whose smoke aerosol release was lower than that of the cigarette core in all grouped samples, or substances whose smoke aerosol release was lower than that of the cigarette core in some grouped samples, were classified as migrating components; the migration rate of migrating components from the cigarette core to the smoke aerosol was calculated.

[0013] This invention is a pioneering creation, establishing a non-target analysis method based on GC-Orbitrap / MS, making it applicable to both heated cigarette core analysis and heated cigarette aerosol analysis, while maintaining comparability. Using this systematic and comparable analytical method, multiple control samples are analyzed. Based on the statistical results, attribution analysis is performed on the components of heated cigarette aerosols, clarifying which are newly generated pyrolysis components during the heating process and which are components that migrate from the core to the aerosol, achieving a comprehensive and systematic analysis of the migration and transformation laws of chemical components in heated cigarettes. Based on the analytical results, technical and data support can be provided for the design and production of heated cigarettes.

[0014] Preferably, in step (2), compounds are screened based on ΔRI≤20, SI≥800, RSI≥800, HRF Score≥90, RHRF Score≥90, and Total Score≥90. Compound Discover 3.2 (ThermoScientific) can be used for qualitative analysis and semi-quantitative analysis of the samples, thus providing a basis for subsequent control analysis.

[0015] Preferably, in step (2), dichloromethane solvent and a mixed standard solution of internal standard are added for solvent extraction. This solvent extraction condition allows for the full extraction of tobacco smoke components, comprehensively reflecting the composition of tobacco smoke.

[0016] More preferably, for each 0.5-1.0g of tobacco powder, 10-20mL of dichloromethane and 80-100μL of internal standard mixed standard solution are added.

[0017] More preferably, for the smoke sample, aerosols from 3-4 heated cigarettes are collected, and 10-20 mL of dichloromethane and 80-100 μL of internal standard mixed solution are added accordingly.

[0018] Using the above extraction conditions, good extraction results can be obtained for both cigarette core and flue gas samples. The extracted solutions can be directly used for GC-Orbitrap / MS analysis, improving sample pretreatment efficiency.

[0019] Preferably, in step (2), the GC-Orbitrap / MS analysis uses a TG-5MS column; the gas chromatography oven temperature program is as follows: initial temperature 40℃ held for 1 min, then increased to 300℃ at a rate of 3℃ / min and held for 30 min; the injection port temperature is 290℃. Using the above-mentioned chromatographic column and chromatographic separation conditions, better component separation effect can be obtained.

[0020] More preferably, the mass spectrometry conditions for GC-Orbitrap / MS analysis are as follows: ionization mode: EI, ionization energy: 70 eV; resolution: 60,000; mass spectrometry acquisition range: 40-400 m / z; transfer line and ion source temperature: 290 °C. These mass spectrometry conditions facilitate comprehensive acquisition and systematic analysis of various compounds.

[0021] The application of the above-mentioned end-to-end quantitative migration and transformation analysis method of chemical components in heated tobacco products in the design of harm reduction and quality improvement of heated cigarettes.

[0022] The above analytical methods can clarify the source and attribution of heated cigarette aerosol components, identify which components are generated by pyrolysis and which migrate from the cigarette core components, and determine the migration rate. This allows for the analysis of the toxicity of these components, thereby enabling the design of harm reduction for heated cigarettes. For the effective components of heated cigarettes, migration rate assessment can provide data support for the optimization of heating methods and products.

[0023] This method can systematically and comprehensively optimize the design for harm reduction and quality improvement of heated cigarettes, effectively solving the problems of blindness and one-sidedness in existing improvement designs.

[0024] Compared with the prior art, the present invention achieves the following beneficial technical effects:

[0025] 1. It achieves true quantitative traceability: upgrading from "whether it exists" to "how much it has, where it comes from, and how much has been transformed", providing unprecedented quantitative accuracy.

[0026] 2. Output data that directly guides decision-making: Clear "migration rate" data can be directly used to compare the differences in compound release efficiency under different formulations or processes; the "new component" list provides clear targets for finding key precursors and blocking harmful substance formation pathways.

[0027] 3. Scientific methodology and reliable results: By using the exact same non-target semi-quantitative method to analyze cigarette cores and aerosols, the comparability of data and the accuracy of calculation results are ensured, forming an analytical closed loop.

[0028] 4. Extremely high application value: This method provides a fundamental tool for precise product harm reduction (reducing the content of precursors of harmful substances in thermal reactions), efficacy assessment (calculating the transfer efficiency of active ingredients), and optimization of heating methods. Attached Figure Description

[0029] Figure 1 This is a high-resolution gas chromatogram of the heated cigarette smoke aerosol in Embodiment 1 of the present invention;

[0030] Figure 2 This is a high-resolution gas chromatogram of the heated cigarette core in Embodiment 1 of the present invention. Detailed Implementation

[0031] Current research on heated cigarettes fails to answer the following key questions: First, regarding the source of aerosol components in the smoke: does a certain component in the aerosol migrate directly from the inherent substances in the cigarette core, or is it newly generated during the heating process? Second, for migrating components, the migration ratio from the cigarette core to the aerosol is unknown. The lack of clarity regarding the essential properties of these aerosol components directly affects the effectiveness and relevance of harm reduction and quality improvement designs for heated cigarettes.

[0032] The technical concept of this invention is to establish a mass spectrometry library of chemical components in tobacco smoke, and to establish a non-target analysis process that is comparable, semi-quantitative, and closed-loop based on gas chromatography-high-resolution mass spectrometry, and to classify and analyze the components of tobacco cores and tobacco aerosols.

[0033] The entire heated cigarette system is a thermal reaction system, and harmful substances originate from three sources: First, they are detected in aerosols but not in the cigarette core; these substances are newly formed and have no migration rate. Second, the amount in aerosols is greater than that in the cigarette core, originating from the breakdown of some precursors in the cigarette core. Third, the amount in aerosols is less than that in the cigarette core; these substances originate from the migration of substances from the cigarette core, possibly from adhesives added during industrial processing. The first two types are collectively referred to as thermally reacting harmful substances.

[0034] This method, through analysis and comparison, identifies which components are present in high concentrations in the aerosol and are either thermally reacted or thermally decomposed; and which components migrate from the cigarette core and are present in lower concentrations in the aerosol than in the core. The findings of this method can provide data support for the design of harm-reduction and quality-improvement processes for heated cigarettes.

[0035] The implementation steps of the end-to-end quantitative migration and transformation analysis method for chemical components of heated non-combustible tobacco products of the present invention are as follows:

[0036] (1) Establish a high-resolution mass spectrometry library of tobacco smoke components.

[0037] In this step, based on the list of tobacco additives and relevant literature, a total of over 749 tobacco smoke component compounds were collected, including 66 alcohols, 27 phenols, 27 ethers, 74 aldehydes, 122 ketones, 10 acetals / ketals, 3 acids / anhydrides, 226 esters, 45 lactones, 30 hydrocarbons, 22 sulfur-containing compounds, and 97 nitrogen-containing compounds. High-resolution mass spectrometry (HMS) was used to acquire these compounds, and the instrument's built-in software was employed to establish a HMS library, thereby increasing the accuracy of qualitative analysis during high-resolution non-target analysis.

[0038] (2) After grinding the cigarette core into powder, solvent extraction was performed. The compounds in the cigarette core were quantitatively analyzed by non-target relative analysis using GC-Orbitrap / MS, and the content of each component in a single cigarette was recorded. The cigarette core was heated and smoked to collect the aerosol of the heated cigarette smoke. Then, the same solvent extraction and GC-Orbitrap / MS analysis were performed to record the release amount of each component in the aerosol of each cigarette.

[0039] The main purpose of this step is to establish a comparable analytical method for non-target systems of heated cigarette cores and smoke aerosols.

[0040] For the cigarette core samples, the samples were finely homogenized, and the internal standard method was used. GC-Orbitrap-MS technology was employed to perform non-target relative quantification of the compounds in the cigarette core (comprehensive and unbiased detection of all detectable compounds), and the content of each component in a single cigarette was recorded.

[0041] Using a linear smoking machine and under strict control of the smoking parameters, cigarette cores from the same batch with known non-target semi-quantitative data were smoked. Cambridge filters and adsorption tubes were used to perform full capture of heated cigarette aerosols, ensuring the collection of as much of the mainstream aerosols (particulate matter and gaseous matter) as possible. All captured aerosol samples underwent pretreatment, and non-target semi-quantitative analysis of aerosol compounds was performed using the same analytical methods as in step 1. The release amount of each component in the aerosol of each cigarette was recorded.

[0042] Specifically, for cigarette core samples, the tobacco shreds from multiple heated cigarettes can be ground into powder. Weigh 0.5~1.0g of the tobacco powder, add 10~20mL of dichloromethane and 80~100μL of internal standard mixed standard solution, vortex for 20~30min, and then filter through a 0.22μm organic phase microporous membrane for GC-Orbitrap / MS analysis.

[0043] For the smoke samples, the particulate matter from 3-4 heated cigarettes can be collected using a Cambridge filter in Canadian deep puff mode (2 puffs per minute, 2 seconds duration, 55 mL volume). After puffing, the Cambridge filter is removed, and 10-20 mL of dichloromethane and 80-100 μL of a mixed standard solution (120 μg / mL) are added. The mixture is sonicated for 20-30 min, filtered through a 0.22 μm organic phase microporous membrane, and then analyzed by GC-Orbitrap / MS.

[0044] Prepare 1000 μg / mL of n-alkanes (C7~C6) 40 The mixture was diluted with dichloromethane to 10 μg / mL and analyzed by GC-Orbitrap / MS.

[0045] The following analysis conditions are uniformly adopted for GC-Orbitrap / MS analysis:

[0046] Gas chromatography conditions: Analytes were separated using a TG-5MS column (30 m × 0.25 mm × 0.25 μm, Thermo Scientific). Helium (99.99% purity) was used as the carrier gas at a flow rate of 1 mL / min. The injection volume was 1 μL. The gas chromatography oven temperature program was as follows: initial temperature 40℃, held for 1 min, then increased to 300℃ at a rate of 3℃ / min, held for 30 min. The injection port temperature was 290℃.

[0047] Mass spectrometry conditions: Ionization mode: EI, ionization energy: 70 eV; resolution: 60000 (FWHM, m / z=200 Da); mass spectrometry acquisition range set to 40-400 m / z, transfer line and ion source temperatures both 290℃.

[0048] Samples were collected using TraceFinder 5.1 (Thermo Scientific).

[0049] Qualitative analysis of the samples was performed using Compound Discover 3.2 (Thermo Scientific).

[0050] The qualitative indicator in chromatography is the difference in retention index ( The retention index (RI) reflects the relative retention behavior of a compound on a specific chromatographic column. It is calculated based on the retention times of two adjacent n-alkanes before and after the retention time of the target compound. The specific calculation formula is shown in formula (1):

[0051] …………(1)

[0052] RT(X): Retention time of the target compound;

[0053] RT(Z), RT(Z+1): Adjacent n-alkanes (C Z and C Z+1 The retention period;

[0054] The formula requires that RT(Z) < RT(X) < RT(Z+1).

[0055] ΔRI is the absolute difference between the experimentally measured retention index and the retention index of the compound recorded in the database. The smaller the ΔRI, the more accurate the qualitative analysis of the target analyte. The screening condition was set to ΔRI ≤ 20.

[0056] Target compounds were screened by controlling several conditions of mass spectrometry qualitative parameters SI, RSI, HRF Score, RHRF Score, and Total Score. The screening conditions were set as follows: SI ≥ 800, RSI ≥ 800, HRF Score ≥ 90, RHRF Score ≥ 90, and Total Score ≥ 90.

[0057] For the screened compounds, four internal standards (d8-styrene, d8-acetophenone, d8-phenylene oxide ... 10 The peak area and content of benzophenone and diisobutyl phthalate (d4-phthalate) were used to perform semi-quantitative analysis of the content of each compound. The transfer rate of each compound was calculated by the ratio of the relative contents of the flue gas and smoke powder.

[0058] (3) End-to-end quantitative calculation and source analysis: Statistical analysis of the obtained data is performed to attribute the newly generated cracked components during the heating process and the components that migrate from the heated cigarette core, and the migration rate is calculated.

[0059] By comparing and analyzing the components of multiple heated cigarette cores and their aerosols, substances that could be accurately quantified in the smoke but not detected in the cigarette core, or substances whose aerosol release was higher than that in the cigarette core, were identified in all grouped samples. These compounds are pyrolysis products formed during the heating process of heated cigarettes.

[0060] Newly generated components identification and precursor prediction: Components detected only in aerosols and confirmed not to be background contaminants are identified as newly generated components. Using thermochemical knowledge, potential precursor substances that may be generated through reactions such as cracking, oxidation, and synthesis are searched. When certain newly generated components are identified as hazardous, quality monitoring of these components and their precursor substances can be implemented to further reduce the harm of smoking heated cigarettes.

[0061] By comparing and analyzing the components of multiple heated cigarette cores and smoke aerosols, we identified substances in all grouped samples whose smoke aerosol release was lower than that in the core, or substances in some grouped samples whose smoke aerosol release was lower than that in the core. These substances are those that migrate from the core to the smoke aerosol.

[0062] Calculate the transfer rate (TR_i) of the migrating component:

[0063] TR_i (%) = (Total release of component i in aerosol / Initial total amount of component i in cigarette core) × 100%.

[0064] Further mass balance and attribution analysis can be conducted. For key compound categories of interest (such as total aldehydes and nicotine), a mass flow diagram from the cigarette core to the aerosol can be drawn to visually demonstrate the migration and regeneration ratios.

[0065] The preferred embodiments described above are illustrated below with specific examples. Unless otherwise specified, the raw materials used in the following embodiments are all commercially available products, and the processing techniques used are all existing technologies.

[0066] Example 1

[0067] This embodiment of the method for end-to-end quantitative migration and transformation analysis of chemical components in heated non-combustible tobacco products selects nine types of heated cigarettes and performs high-resolution non-target analysis of the cigarette core and its aerosol. The specific steps are as follows:

[0068] (1) Based on the list of tobacco additives and related literature, a high-resolution mass spectrometry library of more than 749 tobacco smoke components was collected and established. The high-resolution mass spectrometry library covers: 66 alcohols, 27 phenols, 27 ethers, 74 aldehydes, 122 ketones, 10 acetals / ketals, 3 acids / anhydrides, 226 esters, 45 lactones, 30 hydrocarbons, 22 sulfur-containing compounds, and 97 nitrogen-containing compounds.

[0069] (2) Comparable GC-Orbitrap / MS non-target analysis was performed on heated cigarette cores and smoke aerosols.

[0070] 1. Sample pretreatment

[0071] Smoke samples: Smoke was fully captured using a series connection of filters and adsorption tubes. In Canadian deep puff mode (2 puffs per minute, 2 seconds duration, 55 mL volume), Cambridge filters were used to collect particulate matter from three heated cigarettes, and XAD-4 adsorption tubes were used to collect gaseous matter. The Cambridge filters and adsorption tubes were collected in the same conical flask, and 10 mL of dichloromethane and 80 μL of a mixed internal standard solution (d8-styrene, d8-acetophenone, d...) were added. 10 Benzyl ketone and diisobutyl phthalate (d4-phthalate, each internal standard concentration 120 μg / mL) were sonicated for 20 min, filtered through a 0.22 μm organic phase microporous membrane, and then analyzed by GC-Orbitrap / MS.

[0072] Tobacco powder sample: The tobacco shreds of ten heated cigarettes were ground into powder, 0.5g of tobacco powder was weighed, 10mL of dichloromethane and 80 μL of internal standard mixed standard solution were added (as above), vortexed for 20min, and then filtered through a 0.22μm organic phase microporous membrane for GC-Orbitrap / MS analysis.

[0073] The n-alkane mixture solution is C7~C 40 A dichloromethane solution was used to analyze a 10 μg / mL mixture of n-alkanes using GC-Orbitrap / MS to obtain the retention time of each n-alkanes, and thus the retention index of each target compound.

[0074] 2. Instrumental Analysis

[0075] The gas chromatography conditions for GC-Orbitrap / MS analysis were as follows: analytes were separated using a TG-5MS column (30 m × 0.25 mm × 0.25 μm, Thermo Scientific). Helium (99.99% purity) was used as the carrier gas at a flow rate of 1 mL / min. The injection volume was 1 μL. The gas chromatography oven temperature program was as follows: initial temperature 40 °C, held for 1 min, then increased to 300 °C at a rate of 3 °C / min, and held for 30 min. The injection port temperature was 290 °C.

[0076] Mass spectrometry conditions: Ionization mode: EI, ionization energy: 70 eV; resolution: 60000 (FWHM, m / z=200 Da); mass spectrometry acquisition range set to 40-400 m / z, transfer line and ion source temperatures were both 290℃.

[0077] Samples were collected using TraceFinder 5.1 (Thermo Scientific). Figure 1 High-resolution gas chromatogram of heated cigarette smoke aerosol. Figure 2 High-resolution gas chromatogram of heated cigarette core.

[0078] Qualitative analysis of the samples was performed using Compound Discover 3.2 (Thermo Scientific).

[0079] The screening criteria for the chromatographic qualitative parameter ΔRI are: ΔRI≤20.

[0080] Target compounds were screened by controlling several qualitative parameters of mass spectrometry: SI, RSI, HRF Score, RHRF Score, and Total Score. The screening conditions were set as follows: SI ≥ 800, RSI ≥ 800, HRF Score ≥ 90, RHRF Score ≥ 90, and Total Score ≥ 90. Four internal standards (d8-styrene, d8-acetophenone, d...) were used. 10Semi-quantitative analysis of the content of each compound was performed by analyzing the peak area and content of benzophenone and d4-diisobutyl phthalate. 80 μL of internal standard mixture (all four internal standards were 120 μg / mL) was added to 10 mL of extract, resulting in a final internal standard concentration of 0.96 μg / mL for all internal standards. The retention times of the four internal standards were 8.525 min, 16.194 min, 40.315 min, and 48.937 min, respectively. For target compounds with peak times less than 8.525 min, the relative content was calculated using d8-styrene as the internal standard; for target compounds with peak times between 8.525 and 16.194 min, the relative content was calculated using d8-acetophenone as the internal standard; for target compounds with peak times between 16.194 and 40.315 min, the relative content was calculated using d8-acetophenone as the internal standard. 10 The relative content was calculated using benzophenone as an internal standard; the relative content was calculated using d4-diisobutyl phthalate as an internal standard after the target analyte elution time was after 48.937 min.

[0081] (3) Comparative data analysis

[0082] Statistical analysis was performed on multiple groups of heated cigarette cores and their corresponding smoke aerosol components to identify newly formed pyrolysis components and migrating components. Specifically, substances that were quantitatively detected in the smoke of all grouped samples but not in the cigarette core, or whose smoke aerosol release was higher than that in the cigarette core, were classified as newly formed pyrolysis components.

[0083] In this embodiment, 17 newly formed pyrolysis products were obtained, of which 6 components were below the limit of quantification in the tobacco core, and 11 components had aerosol release amounts higher than those in the tobacco core. The newly formed pyrolysis components are listed in Table 1. The difference between the measured retention index and the standard retention index of each compound in Table 1 is extremely small, ΔRI≤11, meeting the chromatographic qualitative screening conditions, further demonstrating the accuracy of the qualitative analysis of the corresponding compounds.

[0084] Table 1. Compounds produced by pyrolysis

[0085]

[0086]

[0087]

[0088] The results of the ratio of aerosol release per cigarette to core content are listed in Table 2.

[0089] Table 2. Ratio of aerosol release per cigarette to core content in heated cigarettes

[0090]

[0091] Further analysis of the newly generated pyrolysis components revealed that triacetin is a release from the cigarette filter during the heating process. 3-Chloro-1,2-propanediol and acetaldehyde glycerol acetal are substances generated from glycerol during heating. Furans are pyrolysis products of carbohydrates. Based on the characteristics of these newly generated pyrolysis components, quality monitoring or product optimization can be implemented for the corresponding precursors.

[0092] Substances whose flue gas aerosol release is lower than that of the cigarette core in all grouped samples, or substances whose flue gas aerosol release is lower than that of the cigarette core in some grouped samples, are classified as the migrating components; the migration rate of the migrating components from the cigarette core to the flue gas aerosol is calculated.

[0093] In this embodiment, 38 compounds that migrated from the cigarette core to the flue gas aerosol were detected, and are listed in Table 3.

[0094] Table 3. Percentage of aerosol release per cigarette from the core content of heated cigarettes

[0095]

[0096]

[0097]

[0098]

[0099] Table 3 shows that among the nine types of heated cigarettes, the migration rates of nicotine ranged from 20% to 50%, propylene glycol from 10% to 30%, and limonene from 1% to 23%. One sample showed a higher limonene release in its smoke than in the cigarette core, indicating the addition of an additive capable of releasing limonene. For components such as menthone, menthol, isomenthone, menthyl acetate, and caryophyllene, the addition of additives capable of releasing these substances significantly increased their content in the smoke aerosol, reaching multiple times the content of individual components in a single cigarette core. Without additives, the migration rate of individual components ranged from 1% to 90%, varying depending on the individual component and the sample. This result demonstrates that the cigarette core formulation is crucial to the migration rate of some flavor components.

[0100] Example 2

[0101] This embodiment applies the end-to-end quantitative migration and transformation analysis method of chemical components in heated tobacco products to the design of harm reduction and quality improvement for heated cigarettes. Based on the analysis results of the method in Example 1, the hazard analysis of pyrolysis-induced and migrating components is conducted. While meeting the requirements for smoking heated cigarettes, the content of precursor substances or migrating components is reduced as much as possible to achieve the harm reduction design of heated cigarettes. By analyzing the migration rate of flavor components, the design of heated cigarette devices and the composition of the formula are optimized, thereby further improving the smoking experience of heated cigarettes.

[0102] 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 end-to-end quantitative migration and transformation analysis of chemical components in heat-not-burn tobacco products, characterized in that, Includes the following steps: (1) Establish a high-resolution mass spectrometry library of tobacco smoke components; (2) After grinding the cigarette core into powder, solvent extraction was performed. The compounds in the cigarette core were quantitatively analyzed by non-target relative analysis using GC-Orbitrap / MS, and the content of each component in a single cigarette was recorded. The cigarette core was heated and smoked to collect the aerosol of the heated cigarette smoke. Then, the same solvent extraction and GC-Orbitrap / MS analysis were performed to record the release amount of each component in the aerosol of each cigarette. (3) Statistical analysis was performed on multiple groups of heated cigarette cores and corresponding smoke aerosol components to identify newly generated pyrolysis components and migrating components: substances that were quantitatively detected in the smoke of all grouped samples but not detected in the cigarette core, or substances whose smoke aerosol release was higher than that of the cigarette core, were classified as newly generated pyrolysis components; substances whose smoke aerosol release was lower than that of the cigarette core in all grouped samples, or substances whose smoke aerosol release was lower than that of the cigarette core in some grouped samples, were classified as migrating components. Calculate the migration rate of the migrating components from the cigarette core to the flue gas aerosol.

2. The end-to-end quantitative migration and transformation analysis method for chemical components of heated non-combustible tobacco products as described in claim 1, characterized in that, In step (2), compounds were screened out based on ΔRI≤20, SI≥800, RSI≥800, HRF Score≥90, RHRF Score≥90, and Total Score≥90.

3. The end-to-end quantitative migration and transformation analysis method for chemical components of heated non-combustible tobacco products as described in claim 1, characterized in that, In step (2), dichloromethane solvent and internal standard mixed standard solution are added for solvent extraction.

4. The end-to-end quantitative migration and transformation analysis method for chemical components of heated non-combustible tobacco products as described in claim 3, characterized in that, For cigarette core samples, add 10-20 mL of dichloromethane and 80-100 μL of internal standard mixed standard solution for every 0.5-1.0 g of cigarette powder.

5. The end-to-end quantitative migration and transformation analysis method for chemical components of heated non-combustible tobacco products as described in claim 3, characterized in that, For the smoke sample, collect aerosols from 3-4 heated cigarettes and add 10-20 mL of dichloromethane and 80-100 μL of internal standard mixed standard solution accordingly.

6. The end-to-end quantitative migration and transformation analysis method for chemical components of heated non-combustible tobacco products as described in claim 1, characterized in that, In step (2), the GC-Orbitrap / MS analysis used a TG-5MS column; the gas chromatography oven temperature program was: initial temperature 40℃ held for 1 min, then increased to 300℃ at a rate of 3℃ / min and held for 30 min; the injection port temperature was 290℃.

7. The end-to-end quantitative migration and transformation analysis method for chemical components of heated non-combustible tobacco products as described in claim 6, characterized in that, The mass spectrometry conditions for GC-Orbitrap / MS analysis were: ionization mode: EI, ionization energy: 70 eV; Resolution: 60000; mass spectrometry acquisition range set to 40-400 m / z, and transfer line and ion source temperatures both set to 290℃.

8. The application of an end-to-end quantitative migration and transformation analysis method for chemical components of heated non-combustible tobacco products as described in any one of claims 1-7 in the design of harm reduction and quality improvement of heated cigarettes.

Images