Stability evaluation method
By using gas chromatography-mass spectrometry to separate and quantify the aerosol-generating matrix, the problem of long evaluation cycles and strong subjectivity in flavor stability evaluation in existing technologies has been solved, enabling stability assessment and formulation optimization of the aerosol-generating matrix.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-01-20
- Publication Date
- 2026-04-10
AI Technical Summary
Existing methods for evaluating the flavor stability of aerosol-generating matrices are time-consuming and easily affected by subjective human factors, making it impossible to effectively predict the retention capacity of flavor or functional components.
The aerosol-generating matrix was processed in two parts using gas chromatography-mass spectrometry. One part was subjected to gas-liquid equilibrium to obtain the headspace phase, and the other part was used to prepare the detection solution. The two parts were analyzed separately, and the volatile components were identified by the first mass spectrum and the volatility coefficient was calculated to assess the stability.
It provides an objective and quantitative method for stability evaluation, which improves the efficiency of aerosol generation matrix formulation optimization and quality control, and reduces time costs and subjective influences.
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Abstract
Description
Technical Field
[0001] This application relates to the field of evaluation methods, specifically to a stability evaluation method for evaluating the stability of aerosol matrices. Background Technology
[0002] The atomizing device includes a liquid storage container and an atomizer. The liquid storage container is used to load the aerosol generating matrix, and the atomizer generates aerosols by heating the aerosol generating matrix to atomize it.
[0003] However, in actual storage and use, the flavor of the aerosol generating matrix is often difficult to maintain stability. This is because the aerosol generating matrix includes components such as active substances, flavorings, and fragrances. During storage, highly volatile components gradually escape and enter the top space of the reservoir, causing a noticeable decrease in the light, initial aroma (known as the "top note") of the aerosol upon opening compared to its initial state. During use, when the aerosol generating matrix wets the atomizer coil and wicking cotton, the highly volatile components, due to their lower boiling point, preferentially vaporize, resulting in an overly strong initial aroma that is then noticeably diminished by subsequent flavors.
[0004] Currently, methods for assessing the stability of aerosol-generating matrices mainly rely on long-term sample observation and human sensory evaluation. These methods typically take weeks or even months, and the evaluation results are easily influenced by subjective factors, lacking objective quantitative standards. This makes it difficult to provide timely and effective feedback and guidance for the formulation optimization and quality control of aerosol-generating matrices. Summary of the Invention
[0005] This application discloses a stability evaluation method for evaluating the stability of aerosol matrices, in order to solve the problems of existing aerosol generation matrix flavor stability evaluation methods being time-consuming and easily affected by subjective human factors, and unable to effectively predict the retention capacity of flavor or functional components in aerosol generation matrices.
[0006] To solve the above-mentioned technical problems, this application is implemented as follows: This application provides a stability evaluation method for evaluating the stability of an aerosol matrix, comprising the following steps: dividing the aerosol matrix to be tested into two parts, one part being added to a sealed container for gas-liquid equilibrium to obtain a headspace phase, and the other part being used to prepare a detection solution; under preset conditions, analyzing the headspace phase using a gas chromatography-mass spectrometry (GC-MS) to obtain a first mass spectrum; under the preset conditions, analyzing the detection solution using the GC-MS to obtain a second mass spectrum; and determining the volatile components in the aerosol matrix to be tested based on the first and second mass spectra.
[0007] In some embodiments, determining the volatile components in the aerosol generation matrix based on the first mass spectrum and the second mass spectrum includes: determining the constituent components and headspace content information of the headspace phase based on the first mass spectrum, wherein the constituent component information includes several constituent components, and the headspace content information includes the headspace content of each constituent component; determining the liquid phase content information based on the constituent component information of the headspace phase and the second mass spectrum, wherein the liquid phase content information includes the liquid phase content of each constituent component; and determining the volatile components in the aerosol generation matrix based on the headspace content information and the liquid phase content information.
[0008] In some embodiments, determining the volatile components in the aerosol generation matrix based on the headspace content information and the liquid phase content information includes: determining volatility coefficient information based on the headspace content information and the liquid phase content information, wherein the volatility coefficient information includes the volatility coefficient of each of the constituent components; and determining the volatile components in the aerosol generation matrix based on the volatility coefficient information.
[0009] In some embodiments, determining the volatile components in the aerosol generation matrix based on the volatility coefficient information includes: obtaining a preset volatility coefficient; if the volatility coefficient in the volatility coefficient information is greater than or equal to the preset volatility coefficient, then the component corresponding to the volatility coefficient is the volatile component in the aerosol generation matrix.
[0010] In some embodiments, determining the volatile components in the aerosol generation matrix based on the volatility coefficient information includes: arranging the volatility coefficients in the volatility coefficient information in descending order to obtain a volatility sequence; arranging the constituent components corresponding to each volatility coefficient according to the descending order of the volatility coefficients in the volatility sequence to obtain a volatile component sequence; wherein each constituent component in the volatile component sequence uniquely corresponds to a volatility coefficient at the same position in the volatility sequence; and determining the volatile components in the aerosol generation matrix based on the volatile component sequence.
[0011] In some embodiments, determining the volatile components in the aerosol generation matrix based on the volatile component sequence includes: obtaining a preset quantity; and determining the constituent components in the volatile component sequence that are within the first preset quantity as the volatile components in the aerosol generation matrix.
[0012] In some embodiments, the equilibrium temperature for gas-liquid equilibrium is 35~45°C, and the equilibrium time is 25~35 min.
[0013] In some embodiments, the preset conditions include chromatographic conditions; the chromatographic conditions include: a capillary column, a flow rate of 0.9~1.1 mL / min; an injection port temperature of 230~250 ℃, an injection volume of 1.0~1.2µL, a split injection method, and a split ratio of (48~52):1; and a programmed temperature rise to 240~250 ℃.
[0014] In some embodiments, the preset conditions further include mass spectrometry conditions; the mass spectrometry conditions include: a transfer line temperature of 230~250 ℃, an ion source temperature of 220~240 ℃, a quadrupole temperature of 140~160 ℃, and an ionization energy of 60~80 eV.
[0015] In some embodiments, the volume concentration of the aerosol matrix to be tested in the detection solution is 0.8% to 1.2%; and / or, the detection solution further includes at least one of methanol, ethanol, acetonitrile, acetone, and tetrahydrofuran.
[0016] This application discloses a stability evaluation method for assessing the stability of an aerosol matrix, comprising the following steps: dividing the aerosol-generating matrix to be tested into two parts, one part being added to a sealed container for gas-liquid equilibrium to obtain a headspace gas phase, and the other part being used to prepare a detection solution; analyzing the headspace gas phase under preset conditions using gas chromatography-mass spectrometry to obtain a first mass spectrum; analyzing the detection solution under preset conditions using gas chromatography-mass spectrometry to obtain a second mass spectrum; and determining the volatile components in the aerosol-generating matrix to be tested based on the first and second mass spectra. In this application, by performing gas chromatography-mass spectrometry analysis on the headspace gas phase and the detection solution under the same conditions to obtain a first and a second mass spectrum, and by determining the volatile components in the aerosol-generating matrix to be tested based on the first and second mass spectra, it is beneficial to predict the ability of the aerosol-generating matrix to retain flavor or functional components during storage or use. This method overcomes the limitations of traditional sensory evaluation, which is highly subjective and time-consuming, and provides data support for the stability evaluation of aerosol-generating matrices. Detailed Implementation
[0017] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the fixed scope of the present invention.
[0018] It should be understood that the phrase "one embodiment" or "an embodiment" throughout the specification means that a specific feature, structure, or characteristic related to the embodiment is included in at least one embodiment of the invention. Therefore, "in one embodiment" or "in an embodiment" appearing throughout the specification do not necessarily refer to the same embodiment. Furthermore, these specific features, structures, or characteristics can be combined in any suitable manner in one or more embodiments.
[0019] The wicking cotton in the atomizer adsorbs and delivers the aerosol generation matrix to the atomizing core through capillary action. When the atomizing core is powered on, it heats up and rapidly evaporates the aerosol generation matrix into aerosol. The aerosol is then delivered to the user through the airway. The generated aerosol should always maintain the stable flavor characteristics it was designed for. Its flavor should not become noticeably weaker or distorted over time or with increased usage duration; otherwise, it will directly affect the reliability of the product and the user experience.
[0020] However, in actual storage and use, the flavor of the aerosol generating matrix often fails to remain stable. This is because the aerosol generating matrix includes different components such as nicotine, flavorings, and seasonings, each with varying volatility. On one hand, during storage, volatile components gradually escape from the liquid phase and enter the gaseous space at the top of the container, causing a noticeable decrease in the overall flavor, especially the light, initial notes known as the "top notes," compared to the initial state. On the other hand, during use, when the aerosol generating matrix wets the atomizing core and wicking cotton, the volatile components, due to their lower boiling point, preferentially vaporize and concentrate on the wicking cotton fibers and airway walls, causing users to initially experience an overly strong aroma, followed by a rapid weakening of the subsequent flavor, resulting in an unbalanced taste.
[0021] In related technologies, the evaluation methods for the stability of aerosol generating matrices mainly rely on long-term sample observation and human sensory evaluation. This method involves: first, placing aerosol generating matrix samples from different batches or with different formulations in a temperature- and humidity-controlled chamber simulating actual storage conditions, and sampling at different time points. Then, a rigorously trained sensory evaluation team conducts blind testing on the samples at each time point in a compliant evaluation environment. The sensory evaluation team must sequentially smell and experience the samples' odor, taste, aroma intensity, harmony, and overall flavor characteristics, and score or describe them according to a standardized scale. Finally, the sensory data from all sensory evaluation personnel are collected and statistically analyzed. By comparing the differences in flavor characteristics between samples at different time points and the initial sample, the stability of the aerosol generating matrix is determined. This evaluation method typically takes several weeks or even months, and the results are easily influenced by subjective factors, lacking objective quantitative standards, making it difficult to provide timely and effective feedback and guidance for the formulation optimization and quality control of aerosol generating matrices.
[0022] To address the above problems, this application provides a stability evaluation method for evaluating the stability of an aerosol matrix, comprising the following steps 1 to 4: Step 1: Divide the matrix of the aerosol to be tested into two parts. One part is added to a sealed container for gas-liquid equilibrium to obtain the headspace phase, and the other part is used to prepare the detection solution.
[0023] In this step, the matrix for generating the aerosol to be tested is divided into two parts: one part is used to generate the headspace phase, and the other part is used to prepare the detection solution.
[0024] The sealed container can be a headspace sampling vial, which is compatible with a fully automated headspace sampler. The headspace sampling vial is also chemically inert, heat-resistant, and highly airtight, which can prevent sample adsorption, decomposition, or leakage, and ensure the reliability and reproducibility of the gas-liquid equilibrium process.
[0025] A portion of the aerosol matrix to be tested is added to a headspace sample vial, and the vial is sealed. The sealed headspace sample vial is then placed in the sample tray of the headspace autosampler. Under equilibrium conditions, gas-liquid equilibrium is performed. After equilibrium is achieved, the headspace gas phase from the headspace sample vial is extracted.
[0026] The equilibrium temperature for gas-liquid equilibrium is 35–45°C, and the equilibrium time is 25–35 minutes. During gas-liquid equilibrium, the headspace vial will spontaneously tend towards a gas-liquid two-phase equilibrium state. The volatile components of the aerosol-forming matrix will escape into the headspace gas phase, while the less volatile components will remain in the liquid phase. The equilibrium temperature is controlled at 35–45°C to simulate the actual operating and storage temperatures of the aerosol-forming matrix, and the equilibrium time is set at 25–35 minutes to ensure sufficient gas-liquid equilibrium is achieved within the headspace vial.
[0027] Step 2: Under preset conditions, the headspace gas phase is analyzed using a gas chromatograph-mass spectrometer to obtain the first mass spectrum.
[0028] In this step, the separation capabilities of gas chromatography and the identification capabilities of mass spectrometry are used to perform qualitative and quantitative analysis of the constituent components in the headspace gas phase. Specifically, a headspace sampler automatically extracts the headspace gas phase from the headspace vial and injects it into the gas chromatograph inlet. The gas chromatograph inlet is usually set to split mode to accommodate the high volume of the gas sample. The headspace gas phase enters the chromatographic column under the propulsion of the carrier gas. By utilizing the difference in the partition coefficients of the constituent components in the headspace gas phase between the stationary and mobile phases of the chromatographic column, the physical separation of the constituent components in the headspace gas phase is achieved.
[0029] After separation, the constituent components of the headspace gas elute sequentially from the chromatographic column and enter the ion source of the mass spectrometer. The most commonly used is the electron impact ion source, where each component of the headspace gas is bombarded by a high-energy electron beam, generating characteristic ion fragments. These characteristic ion fragments are separated and screened according to their mass-to-charge ratio in a quadrupole mass analyzer. The ion signals are converted into electrical signals and amplified and recorded using detectors such as electron multiplier tubes. The entire analytical process is strictly controlled by the chromatography-mass spectrometry workstation software.
[0030] Finally, the deconvolution algorithm of the chromatography-mass spectrometry workstation software is used to correlate the continuously acquired mass spectra with the chromatographic peaks to generate the first mass spectrum corresponding to the headspace. This first mass spectrum characterizes the retention time, characteristic ion fragment information, and peak area integral data of each component in the headspace phase.
[0031] Step 3: Under preset conditions, the detection solution is analyzed using a gas chromatograph-mass spectrometer to obtain a second mass spectrum.
[0032] Step 3 is the process of physically separating and mass spectrometrically analyzing the components in the detection solution to obtain a second mass spectrum. This process is the same as the process of performing gas chromatography-mass spectrometry analysis on the headspace gas phase described in Step 2. By using the exact same test samples, instrument parameters and test conditions, systematic errors are eliminated, ensuring the accuracy and reliability of subsequent data comparisons.
[0033] Specifically, when acquiring the second mass spectrum, the detection solution is first injected into the gas chromatograph injection port using either the automatic liquid sampler or manual injection. The gas chromatograph injection port employs a split-flow mode, instantly vaporizing the detection solution into a gaseous sample at high temperature. This gaseous sample is then carried by a carrier gas into the chromatographic column for physical separation. Unlike step 2, the gaseous sample formed from the detection solution contains all the constituent components of the aerosol matrix. The constituent components of the detection solution undergo spatial and temporal separation in the chromatographic column based on their boiling points, polarities, and differences in interaction forces with the stationary phase, and then sequentially enter the ion source of the mass spectrometer. Each constituent component of the detection solution is bombarded by a high-energy electron beam, generating characteristic ion fragments. These characteristic ion fragments are separated and screened according to their mass-to-charge ratio in a quadrupole mass analyzer. A detector such as an electron multiplier tube converts the ion signal into an electrical signal, which is then amplified and recorded.
[0034] The entire analysis process is controlled by the chromatography-mass spectrometry workstation software, ensuring that every parameter—from the injection port temperature, column temperature program rate, carrier gas flow rate, ion source temperature, electron energy to the mass spectrometry scan range—is identical to the headspace gas analysis conditions. Finally, the continuously acquired mass spectra are correlated with the chromatographic peaks using the deconvolution algorithm of the chromatography-mass spectrometry workstation software to generate a second mass spectrum corresponding to the detection solution. This second mass spectrum characterizes the retention time, characteristic ion fragment information, and peak area integral data of each component in the detection solution.
[0035] Step 4: Based on the first and second mass spectra, determine the volatile components in the matrix of the aerosol to be tested.
[0036] In this step, the first and second mass spectra are analyzed to determine the constituent components of the headspace phase and the detection solution. The peak area integral data of each constituent component in the headspace phase is compared with the peak area integral data of the same constituent component in the detection solution, or the peak area integral data of each constituent component in the headspace phase is analyzed to determine the volatile components in the matrix of the aerosol to be tested.
[0037] Therefore, the method of this embodiment can quantitatively characterize the volatility of all components in each aerosol generating matrix, providing a key basis for the systematic optimization of aerosol generating matrix formulations and the precise control of product quality. At the same time, the quantitative data provided by this method provides a technical basis for establishing objective quality standards, enabling the quality control of the production process to shift from traditional subjective experience judgment to precise management based on scientific data. This solves the problems of time cost and uncertainty caused by subjective evaluation resulting from the reliance on long-term stability tests in traditional methods, thereby improving product development efficiency and quality control level.
[0038] In some embodiments, determining the volatile components in the aerosol generation matrix based on the first mass spectrum and the second mass spectrum includes the following steps 41 to 43.
[0039] Step 41: Determine the constituent components and headspace content information of the headspace phase based on the first mass spectrum. The constituent component information includes several constituent components, and the headspace content information includes the headspace content of each constituent component.
[0040] In this step, the first mass spectrum records the signal response of each component in the headspace gas phase on the gas chromatograph-mass spectrometer. Qualitative and quantitative analysis of all components in the headspace gas phase is achieved by using the retention time, characteristic ion fragment information, and peak area integral data for each component. Specifically, by comparing the retention time and characteristic ion fragment information of each component with a standard mass spectrometry database (such as the NIST database), the specific chemical substance name or molecular formula corresponding to each chromatographic peak can be uniquely matched and identified, thus determining the component information. Simultaneously, under constant instrument conditions, the peak area integral data can be considered as the headspace content of each component in the headspace gas phase.
[0041] Step 42: Determine the liquid phase content information based on the composition information of the headspace phase and the second mass spectrum, wherein the liquid phase content information includes the liquid phase content of each composition component.
[0042] In this step, the second mass spectrum is compared with a standard mass spectrometry database (such as the NIST database) to uniquely match and identify the specific chemical substance name or molecular formula corresponding to each chromatographic peak in the second mass spectrum. At the same time, the peak area integral data in the second mass spectrum can be regarded as the liquid phase content information of each component in the detection solution. From the liquid phase content information of each component in the detection solution, the liquid phase content information of the headspace components in the second mass spectrum is screened out.
[0043] Step 43: Determine the volatile components in the matrix of the aerosol to be tested based on the headspace content information and the liquid phase content information.
[0044] This step determines the tendency of the constituent components in the aerosol generation matrix to volatilize from the liquid phase to the gas phase by analyzing headspace content information and liquid phase content information. In some embodiments, step 43 determines the volatile components in the aerosol generation matrix based on headspace content information and liquid phase content information, which is achieved by implementing steps 431 to 432.
[0045] Step 431: Determine the volatility coefficient information based on the headspace content information and the liquid phase content information. The volatility coefficient information includes the volatility coefficient of each constituent component.
[0046] Step 432: Determine the volatile components in the matrix of the aerosol to be tested based on the volatility coefficient information.
[0047] In steps 431 to 432, when the first mass spectrum and the second mass spectrum have common constituent components, the first peak area corresponding to these common constituent components in the first mass spectrum and the second peak area in the second mass spectrum are extracted respectively.
[0048] Dividing the area of the first peak by the area of the second peak yields the volatility coefficient of the common constituent component. The magnitude of this volatility coefficient reflects the ease with which the constituent component escapes from the aerosol-generating matrix. A larger volatility coefficient indicates that the constituent component is more easily volatilized and lost from the aerosol-generating matrix, and its stability within the aerosol-generating matrix is worse. Conversely, a smaller volatility coefficient indicates that the aerosol-generating matrix tends to remain within the aerosol-generating matrix, and its stability is better.
[0049] After obtaining the volatility coefficients of each aerosol-generating matrix in the headspace phase, a comprehensive judgment can be made on the overall stability of the aerosol-generating matrix.
[0050] In some embodiments, step 432 determines the volatile components in the aerosol generation matrix based on the volatility coefficient information, including steps 4321 to 4322.
[0051] Step 4321: Obtain the preset volatility coefficient. This preset volatility coefficient is the standard for determining whether a component is a volatile component.
[0052] Step 4322: If the volatility coefficient in the volatility coefficient information is greater than or equal to the preset volatility coefficient, then the component corresponding to the volatility coefficient is the volatile component in the aerosol generation matrix to be tested.
[0053] In this step, the volatility coefficient of each component in the headspace phase is compared one by one with the preset volatility coefficient. If the volatility coefficient of a component is greater than or equal to the preset volatility coefficient, it proves that the volatility of the component meets the definition standard for easy volatility, and therefore the component is determined to be an easy-to-volatile component. If the volatility coefficient of a component is less than the preset volatility coefficient, it proves that the volatility of the component does not meet the definition standard for easy volatility, and therefore the component is determined to be a non-volatile component. This method can efficiently, objectively, and repeatedly screen out easy-to-volatile components from several components, eliminating the subjectivity of manual judgment and ensuring the consistency of the test results.
[0054] When the volatility coefficient of a constituent component is greater than or equal to a preset volatility coefficient, or when the difference in volatility coefficients between different constituent components is large, it indicates that some constituent components in the aerosol generating matrix may volatilize prematurely, leading to a decline in product performance. Therefore, based on the volatility coefficients of each constituent component, researchers can not only objectively assess the stability of existing formulations, but also make targeted adjustments to the formulation composition or process parameters. For example, they can suppress the escape of volatile components by replacing active substances with those having low volatility coefficients, adding stabilizers, changing carrier materials, or optimizing packaging methods, thereby improving product stability.
[0055] In some other embodiments, step 432, which determines the volatile components in the aerosol generation matrix based on the volatility coefficient information, can also be achieved by implementing steps 4323 to 4324.
[0056] Step 4323 arranges the volatile coefficients in the volatile coefficient information in descending order to obtain the volatile sequence.
[0057] Step 4324: Arrange the constituent components corresponding to each volatile coefficient according to the order of volatile coefficients from largest to smallest in the volatile sequence to obtain the volatile component sequence; wherein each constituent component in the volatile component sequence is uniquely associated with the volatile coefficient at the same position in the volatile sequence.
[0058] Step 4325: Determine the volatile components in the matrix of the aerosol to be tested based on the volatile component sequence.
[0059] In this embodiment, step 4323 first arranges the volatility coefficients of all components in descending order to generate a volatility sequence, which represents the change in the volatility of all constituent components from strong to weak; step 4324, according to this order, simultaneously arranges the constituent components corresponding to these volatility coefficients in the same order to generate a volatile component sequence, in which the constituent components in the volatile component sequence are mapped one-to-one with the volatility coefficient information in the volatility sequence.
[0060] In some embodiments, step 4325, which determines the volatile components in the aerosol generation matrix based on the volatile component sequence, can be achieved by implementing the following steps: Obtain a preset quantity; identify the components in the volatile component sequence that are within the first preset quantity as the volatile components in the aerosol generation matrix to be tested.
[0061] In this embodiment, by selecting a predetermined number of components that rank highly in the volatile component sequence as volatile components, this method can screen out a predetermined number of relatively most volatile components in the aerosol generation matrix to be tested, and has the characteristics of high flexibility and strong adaptability.
[0062] In some embodiments, the aerosol generating matrix to be tested is divided into two parts. One part is added to a sealed container for gas-liquid equilibration. The volume of the aerosol generating matrix to be tested added to the sealed container is 2-5 mL, and the volume of the sealed container is 15-25 mL. The other part is used to prepare a detection solution. The volume of this other part is 2-5 mL. The detection solution includes the other part of the aerosol generating matrix to be tested and a solvent. The solvent is at least one of methanol, ethanol, acetonitrile, acetone, and tetrahydrofuran. The volume concentration of the detection solution is 0.8-1.2%. This volume concentration of the detection solution is within the detection range of the gas chromatograph-mass spectrometer, which can improve the sensitivity of the test.
[0063] In this embodiment, a headspace vial with a volume of 15-25 mL provides ample space for the escape of volatile components and gas phase enrichment. Adding 2-5 mL of the aerosol to be tested to form a matrix allows the headspace gas content to reach the detection range of the gas chromatograph-mass spectrometer, thereby improving the sensitivity of the test.
[0064] In some embodiments, the volume of the aerosol generation matrix to be tested added to the sealed container is controlled within 2 mL, while the volume of the sealed container is selected as 20 mL.
[0065] In some embodiments, the preset conditions include chromatographic conditions and mass spectrometry conditions. The chromatographic conditions include: a capillary column, a flow rate of 0.9–1.1 mL / min; an injection port temperature of 230–250 °C, an injection volume of 1.0–1.2 µL, a split injection method with a split ratio of 48–52:1; and a programmed temperature rise to 240–250 °C.
[0066] The process of heating to 240-250 ℃ further includes: (1) holding at an initial temperature of 38-42 ℃ for 2-5 min; (2) heating to 190-210 ℃ at a heating rate of 6-8 ℃ / min and holding for 4-6 min; (3) heating to 230-250 ℃ at a heating rate of 18-22 ℃ / min and holding for 15-18 min; and (4) heating to 240-250 ℃ at a heating rate of 8-12 ℃ / min and holding for 17-20 min.
[0067] The mass spectrometry conditions included: transfer line temperature of 230–250 °C, ion source temperature of 220–240 °C, quadrupole temperature of 140–160 °C, and ionization energy of 60–80 eV.
[0068] In some embodiments, the capillary column can be a DB-WAX type with a diameter of 30 m × 0.25 mm × 0.25 µm.
[0069] It should be explained that the DB-WAX capillary column, as a polar chromatographic column, has high selectivity for polar compounds, making it particularly suitable for the separation of nicotine and various polar flavor components. A size setting of 30 m × 0.25 mm × 0.25 µm optimizes analysis time while ensuring separation efficiency. The carrier gas flow rate of 0.9–1.1 mL / min, combined with the programmed temperature conditions, ensures sufficient focusing and separation of low-boiling-point components (such as volatile aromatic substances) by initially maintaining a temperature of 38–42℃ for 2–5 min. Subsequently, a temperature increase of 6–8℃ / min to 190–210℃ and holding for 4–6 min separates medium-boiling-point components (such as flavorings). Finally, a temperature increase of 18–22℃ / min to 230–250℃ and holding for 15–20 min ensures complete elution of high-boiling-point components such as certain nicotine salts and non-volatile additives.
[0070] In addition, the injection port temperature of 230~250℃, combined with an injection volume of 1.0~1.2µL and a split ratio of (48~52):1, can achieve instantaneous and complete vaporization of the sample, while avoiding excessive injection that could lead to column overload or ion source contamination, thus ensuring peak symmetry and quantitative accuracy.
[0071] In some embodiments, the transfer line temperature in the mass spectrometry conditions is 230~250°C, which can prevent high-boiling-point substances from condensing during the transfer process. The combination of the ion source temperature of 220~240°C and the electron bombardment energy of 60~80 eV optimizes the ionization efficiency of various compounds, while the quadrupole temperature of 140~160°C ensures the stability and resolution of the mass analyzer.
[0072] Based on the above chromatographic and mass spectrometric conditions, gas chromatography-mass spectrometry analysis was performed, achieving full-range coverage detection from low-boiling-point substances to high-boiling-point nicotine and additives. Furthermore, the sensitivity and reproducibility of the analytical process were improved by controlling the temperature program and ionization conditions.
[0073] Based on the above chromatographic and mass spectrometric conditions, this embodiment also includes a method for obtaining a first mass spectrum and a second mass spectrum, comprising the following steps: Take 2 mL of the aerosol matrix to be tested and place it in a 20 mL headspace vial. Seal the vial and place it in the sample tray of the headspace autosampler for equilibration at 40°C for 30 min to allow the gas and liquid phases to reach equilibrium. After equilibration, use a gas-tight syringe to extract the headspace gas phase and pass it into a gas chromatograph-mass spectrometer for analysis.
[0074] Take 2 mL of the same aerosol matrix as the test sample and dilute it with ethanol to 200 mL to prepare the detection solution. Analyze this detection solution using a gas chromatography-mass spectrometry (GC-MS) system. It should be noted that the analytical methods and instrument parameters are the same when performing gas chromatography-mass spectrometry (GC-MS) analysis on the headspace gas phase or the detection solution, respectively. Specifically, 1.0 µL of headspace gas phase or detection solution is injected into the gas chromatography system using an autosampler in a split injection mode, with a split ratio set to 50:1 to avoid column overload and ensure sharp chromatographic peaks. The headspace gas phase or detection solution is instantly and completely vaporized upon entering the injection port at a temperature set to 240 °C, forming a homogeneous gaseous mixture. This gaseous mixture is then carried by a carrier gas (flow rate 1.0 mL / min) into the chromatographic column (30 m × 0.25 mm × 0.25 µm DB-WAX polar capillary column) for separation. During separation, the column is programmed to run at 40 °C for 5 min, then increased to 190–210 °C at a rate of 6–8 °C / min and held for 4–6 min; finally, the temperature is increased to 18–22 °C. The temperature was increased to 230-250 °C at a rate of ℃ / min and held for 15-18 min; then increased to 240-250 °C at a rate of 8-12 °C / min and held for 17-20 min. During the heating process, the constituent components with different boiling points were separated sequentially. The constituent components flowed out of the chromatographic column sequentially with the carrier gas and immediately entered the mass spectrometer sequentially through the transfer line maintained at 240 °C.
[0075] In the mass spectrometer, each component first reaches an ion source at 230 °C, where it is ionized by electron bombardment at 70 eV, generating characteristic fragment ions. These fragment ions are then introduced into a quadrupole mass analyzer with a temperature controlled at 150 °C for mass separation and screening, ensuring the stability and accuracy of the analysis. Finally, the ion signals are acquired by the detector, integrated and analyzed by the data processing system, yielding chromatograms and corresponding mass spectra. The deconvolution algorithm in the chromatography-mass spectrometry workstation software is used to correlate the mass spectra with the chromatographic peaks, generating a first mass spectrum corresponding to headspace and a second mass spectrum corresponding to the detection solution.
[0076] To make the inventive objectives, technical solutions, and beneficial effects of this application clearer, the application is further described below with reference to embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of this application.
[0077] Example 1 (1) Preparation of headspace gas phase Take 2 mL of "tropical fruit" flavored e-liquid and place it in a 20 mL headspace vial. Seal the vial and equilibrate at 40°C for 30 min to allow the gas and liquid phases to fully reach equilibrium. Then, use an airtight syringe to extract the headspace phase.
[0078] (2) Analysis of headspace phase The headspace gas phase was passed into a gas chromatograph-mass spectrometer for analysis to obtain the first mass spectrum.
[0079] (3) Preparation of detection solution Take 2 mL of the same batch of "tropical fruit" flavored e-liquid, dilute it with methanol to 200 mL, and prepare the test solution.
[0080] (4) Analytical detection solution The test solution was passed into a gas chromatograph-mass spectrometer for analysis to obtain a second mass spectrum.
[0081] It should be noted that the exact same test conditions were used for gas chromatography-mass spectrometry analysis of the headspace gas and the detection: column: DB-WAX (30 m × 0.25 mm × 0.25 µm); flow rate: 1.0 mL / min; injection port temperature: 240℃; injection volume: 1.0 µL, split injection (split ratio 50:1); temperature program: 40℃ for 3 min, increase to 200℃ at 7℃ / min and hold for 5 min, increase to 240℃ at 20℃ / min and hold for 18 min; transfer line temperature: 240℃; ion source temperature: 230℃; quadrupole temperature: 150℃; ionization energy: 70 eV.
[0082] (5) Calculate the volatility coefficient Based on the first mass spectrum, the constituent components in the headspace gas phase were determined to include ethyl acetate, linalool, and vanillin. The first peak areas of ethyl acetate, linalool, and vanillin in the first mass spectrum were calculated, and the second peak areas of ethyl acetate, linalool, and vanillin in the second mass spectrum were calculated. Based on the first and second peak areas of each constituent component, the volatility coefficients of ethyl acetate, linalool, and vanillin were calculated, and the results are shown in Table 1.
[0083] Table 1
[0084] As shown in Table 1, in the "tropical fruit" flavored e-liquid, ethyl acetate has the highest volatility coefficient, making it relatively volatile and easily lost during storage, leading to a weakening of the fruity aroma. Vanillin, on the other hand, has the lowest volatility coefficient, allowing it to be stably retained in the aerosol-forming matrix and maintain its flavor for a longer period. Therefore, it can be concluded that with prolonged storage, the fresh fruit flavor will significantly weaken, while the creamy aroma will remain strong. Based on these results, the researchers replaced part of the ethyl acetate in the "tropical fruit" flavored e-liquid with ethyl butyrate, which has a lower volatility coefficient (approximately 45). After 30 days of storage, the flavor fidelity of the new formulation including ethyl butyrate was improved compared to the "tropical fruit" flavored e-liquid, indicating that the method described in this application can effectively guide formulation optimization.
[0085] Comparative Example 1: Traditional Sensory Evaluation The same e-liquid samples as in Example 1 were distributed to the sensory evaluation team and evaluated on day 1 and day 30 after opening (stored at room temperature). The sensory evaluation team generally agreed that the fresh fruit flavor of the e-liquid samples was significantly reduced after 30 days, while the milky aroma remained strong. This result was consistent with the prediction in Example 1, but this method is time-consuming (30 days), highly subjective, and cannot be quantitatively evaluated.
[0086] Comparative Example 2: Conventional Gas Chromatography-Mass Spectrometry (GC-MS) Analysis Take 2 mL of the same e-liquid as in Example 1, dilute it with methanol to 200 mL to obtain an e-liquid solution, and perform gas chromatography-mass spectrometry analysis on the e-liquid solution of Comparative Example 2 according to the method for analyzing the detection solution in Example 1. Obtain the mass spectrum corresponding to the e-liquid solution of Comparative Example 2. The mass spectrum corresponding to the e-liquid solution of Comparative Example 2 is the same as the second mass spectrum of Example 1. Based on the mass spectrum corresponding to the e-liquid solution of Comparative Example 2, only the presence of ethyl acetate, linalool and vanillin can be confirmed, but the volatility differences of each component cannot be reflected. Therefore, it does not have the ability to evaluate stability and predict flavor changes.
[0087] It should be noted that the various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.
[0088] Although alternative embodiments of the present invention have been described, those skilled in the art, upon learning the basic inventive concept, can make further changes and modifications to these embodiments. Therefore, the appended claims are intended to be interpreted as including the alternative embodiments as well as all changes and modifications falling within the scope of the embodiments of the present invention.
[0089] Finally, it should be noted that in this document, relational terms such as "first" and "second" are used merely to distinguish one entity from another, and do not necessarily require or imply any such actual relationship or order between these entities. Furthermore, the terms "comprising," "including," or any other variations thereof are intended to cover non-exclusive inclusion, such that an article or terminal device that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such an article or terminal device. Without further limitations, an element defined by the phrase "comprising one..." does not exclude the presence of other identical elements in the article or terminal device that includes that element.
[0090] The technical solution provided by the present invention has been described in detail above. Specific examples have been used to illustrate the principle and implementation of the present invention. At the same time, for those skilled in the art, there will be changes in the specific implementation and application scope based on the principle and implementation of the present invention. Therefore, the content of this specification should not be construed as a limitation of the present invention.
Claims
1. A stability evaluation method characterized by comprising: The stability evaluation method is used for evaluating the stability of an aerosol substrate, and comprises the following steps: The aerosol generating substrate to be tested is divided into two parts, one of which is added to a sealed container for gas-liquid equilibrium to obtain a headspace gas phase, and the other is used to prepare a detection solution; Under preset conditions, the headspace gas phase is analyzed by using a gas chromatograph mass spectrometer to obtain a first mass spectrum; Under the preset conditions, the detection solution is analyzed by using the gas chromatograph mass spectrometer to obtain a second mass spectrum; According to the first mass spectrum and the second mass spectrum, the volatile component in the aerosol generating substrate to be tested is determined.
2. The stability evaluation method according to claim 1, characterized by, According to the first mass spectrum and the second mass spectrum, the volatile component in the aerosol generating substrate to be tested is determined, comprising: According to the first mass spectrum, the constituent component information and the headspace content information of the headspace gas phase are determined, wherein the constituent component information comprises a plurality of constituent components, and the headspace content information comprises the headspace content of each constituent component; According to the constituent component information of the headspace gas phase and the second mass spectrum, liquid content information is determined, wherein the liquid content information comprises the liquid content of each constituent component; According to the headspace content information and the liquid content information, the volatile component in the aerosol generating substrate to be tested is determined.
3. The stability evaluation method according to claim 2, characterized by, According to the headspace content information and the liquid content information, the volatile component in the aerosol generating substrate to be tested is determined, comprising: According to the headspace content information and the liquid content information, volatility coefficient information is determined, and the volatility coefficient information comprises the volatility coefficient of each constituent component; According to the volatility coefficient information, the volatile component in the aerosol generating substrate to be tested is determined.
4. The stability evaluation method according to claim 3, characterized by, According to the volatility coefficient information, the volatile component in the aerosol generating substrate to be tested is determined, comprising: A preset volatility coefficient is obtained; If the volatility coefficient in the volatility coefficient information is greater than or equal to the preset volatility coefficient, the constituent component corresponding to the volatility coefficient is the volatile component in the aerosol generating substrate to be tested.
5. The stability evaluation method according to claim 3, characterized by, According to the volatility coefficient information, the volatile component in the aerosol generating substrate to be tested is determined, comprising: The volatility coefficients in the volatility coefficient information are arranged in descending order to obtain a volatility sequence; According to the arrangement order of the volatility coefficients in the volatility sequence from large to small, the constituent components corresponding to the respective volatility coefficients are arranged to obtain a volatile component sequence; wherein each constituent component in the volatile component sequence is uniquely corresponding to the volatility coefficient at the same sequence position in the volatility sequence; According to the volatile component sequence, the volatile component in the aerosol generating substrate to be tested is determined.
6. The stability evaluation method according to claim 5, characterized by, According to the volatile component sequence, the volatile component in the aerosol generating substrate to be tested is determined, comprising: A preset number is obtained; The constituent components in the volatile component sequence arranged within the preset number are determined as the volatile components in the aerosol generating substrate to be tested.
7. The stability evaluation method according to any one of claims 1 to 6, characterized by, The equilibrium temperature when the gas-liquid equilibrium is performed is 35-45℃, and the equilibrium time is 25-35 min.
8. The stability evaluation method according to any one of claims 1 to 6, characterized by, The preset conditions include chromatographic conditions; The chromatographic conditions include: The chromatographic column is a capillary column, the flow rate is 0.9-1.1 mL / min, the injection port temperature is 230-250 DEG C, the injection volume is 1.0-1.2 mu L, the injection mode is split injection, and the split ratio is (48-52):1; and the temperature is programmed to 240-250 DEG C.
9. The stability evaluation method according to any one of claims 1 to 6, characterized by, The preset conditions further include mass spectrometric conditions; The mass spectrometric conditions include: the transfer line temperature is 230-250 DEG C, the ion source temperature is 220-240 DEG C, the quadrupole temperature is 140-160 DEG C, and the ionization energy is 60-80 ev.
10. The stability evaluation method according to any one of claims 1 to 6, characterized by, The volume concentration of the aerosol matrix to be detected in the detection solution is 0.8%-1.2%. And / or, the detection solution further includes at least one of methanol, ethanol, acetonitrile, acetone, and tetrahydrofuran.