Method for qualitatively and quantitatively analyzing new psychoactive substances in tobacco tar through in-situ ionization-quadrupole time-of-flight mass spectrometry

Abstract

The invention discloses a method for qualitatively and quantitatively analyzing new psychoactive substances in tobacco tar through in-situ ionization-quadrupole rod time-of-flight mass spectrometry, an electronic tobacco tar sample does not need to be pretreated and can be directly diluted with an internal standard solution, then in-situ ionization-quadrupole rod time-of-flight high-resolution mass spectrometry analysis can be carried out, and only several minutes are needed. The method can obtain comprehensive information of a complex electronic cigarette liquid sample at m / z 50-1000Da to realize qualitative analysis, can make a standard curve through an internal standard method to carry out accurate quantification, and realizes qualitative and quantitative analysis at the same time in an ultra-fast manner. The rapid, accurate and high-sensitivity qualitative and quantitative analysis method is established by taking the new psychoactive substances in the electronic cigarette liquid as research objects, and technical support can be provided for rapid screening of the new psychoactive substances.

Description

Technical Field

[0001] The present invention relates to the field of new psychoactive substances detection, and in particular to a method for qualitatively and quantitatively analyzing new psychoactive substances in tobacco oil by in-situ ionization-quadrupole time-of-flight high-resolution mass spectrometry. Background Art

[0002] In recent years, as a new smoking method, the popularity of e-cigarettes has rapidly increased worldwide and has become a new choice for many smokers. Compared with traditional tobacco products, e-cigarettes are labeled as "less harmful", however, their actual impact and potential risks still cause widespread controversy and concern. E-cigarette oils usually contain a variety of flavor additives to give them an attractive aroma. The masking ability of these aromas makes it difficult to detect potential new psychoactive substances (NPS) such as etomidate, synthetic cannabinoids, fentanyl and its analogs.

[0003] New psychoactive substances are known for their diverse chemical structures and properties, which often circumvent existing legal regulations through minor structural changes. This trend makes it difficult to effectively monitor the use and impact of NPS, posing potential risks to public health and safety. For example, the ever-changing nature of synthetic cannabinoids makes it difficult for regulators to accurately define and regulate them, while the potent nature of fentanyl-like substances makes it extremely easy to cause serious health hazards and overdose risks when they are present in smoking products. Therefore, a deep understanding of the composition of new psychoactive substances in e-cigarette oils and their concentration changes not only provides researchers with a scientific basis for identifying their hazards, but also lays the foundation for regulatory authorities to formulate corresponding policies and standards.

[0004] In this context, the analysis and monitoring of new psychoactive substances in e-cigarette oils has become increasingly important. Among the existing technologies, most use gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS) for detection. For example, the following document describes the use of GC-MS and LC-MS to detect new psychoactive substances such as etomidate and synthetic cannabinoids in matrices such as e-cigarette oil, hair and urine. Among these methods, the treatment of e-cigarette oil often requires dilution, ultrasonication, centrifugation, filtration and then filling into a sample vial for analysis. For example, document [1] published in the 2023 issue of Criminal Technology describes the pretreatment steps of the oil: weigh about 10 mg of e-cigarette oil, place it in a 15 mL polyethylene centrifuge tube, add 10 mL of methanol, vortex mix for 15 seconds, ultrasonically extract for 20 minutes, cool to room temperature, centrifuge at high speed, filter the supernatant through a 0.22 μm filter membrane, dilute with methanol, and transfer 1 mL to a sample bottle for HPLC MS / MS analysis. In addition to the pre-treatment steps including dilution, extraction and filtration, it also takes about an hour to prepare the mobile phase, chromatographic column and equilibrate the instrument state, plus the instrument acquisition time of 10 to 20 minutes. The whole process takes at least an hour or even several hours.

[0005] Reference list:

[0006] [1] Jiao Taifeng, Li Yaqing, Cheng Lianghong, et al. Rapid determination of 58 synthetic cannabinoids in e-cigarette oil by HPLC-MS / MS[J]. Criminal Technology, Issue 1, 2023.

[0007] [2] Wu Junjin, Liu Yao, Liao Shuchun, et al. Detection of new psychoactive substance etomidate in e-cigarette oil, hair and urine[J]. Chinese Journal of Forensic Medicine, 2024, 39(1): 59-61.

[0008] [3]Jung YK, You SY, Kim SY, et al. Simultaneous determination of etomidate and its major metabolite, etomidate acid, in urine using dilute andshoot liquid chromatography-tandemmass spectrometry[J]. Molecules, 2019, 24(24):4459.

[0009] [4] Yum H, Jeong S, Jang M, et al. Fast and reliable analysis ofveterinary metomidate and etomidate in human blood samples by liquidchromatography-tandem mass spectrometry(LC-MS / MS) in a postmortem case[J]. JForensic Sci, 2021, 66(6): 2532-2538. Summary of the invention

[0010] The technical problem to be solved by the present invention is to provide a method for qualitatively and quantitatively analyzing new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight mass spectrometry in view of the deficiencies in the above-mentioned prior art, which has simple operation, fast analysis speed and good accuracy.

[0011] In order to solve the above technical problems, the technical solution adopted by the present invention is as follows:

[0012] A method for qualitatively and quantitatively analyzing new psychoactive substances in e-liquid by in-situ ionization-quadrupole time-of-flight mass spectrometry, characterized in that the electronic cigarette oil sample is diluted with an internal standard solution to obtain a sample solution for injection, and then analyzed by in-situ ionization-quadrupole time-of-flight high-resolution mass spectrometry to obtain a chromatogram of a target substance and an internal standard substance; by extracting the hydrogenation peaks [M+H] of the target substance and the internal standard substance within the acquisition time range + The chromatographic peaks are qualitatively judged within the theoretical accurate molecular weight error of ±10ppm, and then the new psychoactive substances in the e-cigarette oil samples are quantitatively analyzed by the internal standard method in combination with the standard curve;

[0013] The internal standard solution is prepared by dissolving one or more internal standard substances in a mixed solvent of water and an organic solvent, and the internal standard substance is an analogue or isotope marker of a new psychoactive substance;

[0014] The in-situ ionization source adopts a high-resolution in-situ probe ionization mass spectrometry system, with a probe sampling time of 20 to 40 milliseconds, an ionization time of 120 to 200 milliseconds, a probe speed of 200 to 300 mm / milliseconds, a sampling position (i.e., the probe descent height) of 44 to 48 mm, and a discharge voltage of 2 to 3.5 kV; the quadrupole time-of-flight mass spectrometry conditions are a positive ion full scan mode, a desolvation temperature (DL temperature) of 150 to 350°C, a heating module temperature (i.e., the sampling cone heating temperature) of 30 to 50°C, a cycle time (i.e., the time required to collect a point on the chromatogram) of 20 to 200 milliseconds, a scanning mass range of 50 to 1000 Da, and a collection time of 0.1 to 0.5 minutes.

[0015] According to the above scheme, new psychoactive substances include etomidate and its analogs, and synthetic cannabinoids. Specifically, etomidate and its analogs such as isoprenaline, medetomidine, propamate, etc.; synthetic cannabinoids such as 3,3-dimethyl-2-[1-(5-fluoropentyl) indole-3-carboxamido] butyric acid methyl ester, 3,3-dimethyl-2-[1-(4-fluorobutyl) indazole-3-carboxamido] butyric acid methyl ester, N-(1-methyl-1-phenylethyl)-1-(5-fluoropentyl) indazole-3-carboxamide, etc., contain benzoyl indoles, phenylacetyl indoles, naphthoyl indoles, cyclohexyl phenols and naphthoyl pyrrole compounds in their structures.

[0016] According to the above scheme, the e-cigarette oil sample is diluted 100 to 1000 times with the internal standard solution, and the concentration of the internal standard solution is 400 to 600 μg / L.

[0017] According to the above scheme, the standard solution used to draw the standard curve is prepared from the standard sample of the new psychoactive substance and the internal standard solution. The concentration of the target substance (i.e., the new psychoactive substance) in the standard solution is in the range of 50 to 5000 μg / L.

[0018] According to the above scheme, the mixed solvent used to prepare the internal standard solution is a mixture of water and an organic solvent in a volume ratio of 1:1 to 3:1, and the organic solvent is selected with a boiling point lower than 100°C.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] (1) Compared with traditional GC-MS and LC-MS methods and in situ ionization mass spectrometry technology, the present invention can achieve ultra-fast qualitative and quantitative analysis of new psychoactive substances in e-cigarette oil samples. It only takes 5 minutes or less from sample preparation to obtaining chromatograms, which can accurately complete the comprehensive qualitative and quantitative evaluation of complex mixture samples such as unknown e-cigarette oil.

[0021] (2) The present invention adopts in-situ ionization technology. The sample does not need to be pre-treated. It only needs to be diluted with an internal standard solution and then directly analyzed through an ionization source, which greatly reduces sample loss. It can identify new psychoactive substances at extremely low concentrations and accurately obtain information on target new psychoactive substances in a relatively short time. It greatly improves the sensitivity and accuracy of detection and can ensure that even in complex e-cigarette oil samples, trace amounts of psychoactive substances can be effectively identified.

[0022] (3) Compared with traditional methods, the present invention is more accurate in identifying new psychoactive substances contained in e-cigarette oils, can quickly identify and quantify various new psychoactive substances in the oils, has a low risk of misjudgment, and has high reliability of detection results. It also has the ability to detect multiple new psychoactive substances simultaneously, and can detect multiple new psychoactive substances simultaneously in one analysis, which gives it a significant advantage in processing complex e-cigarette oil samples, not only saving time but also providing more comprehensive information support. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 The standard solution in Example 1 (the concentrations of etomidate and propamate are both 50 μg / L) in [M+H] + The extracted chromatograms have a theoretically accurate molecular weight error within ±10ppm.

[0024] Figure 2 The standard curves are drawn when the concentrations of the standard solutions in Example 1 are 50 μg / L, 100 μg / L, 200 μg / L, 500 μg / L, 1000 μg / L, 2000 μg / L and 5000 μg / L, respectively.

[0025] Figures 3 to 5 The following are the values ​​of etomidate and propamate in the three electronic cigarette oil samples 1#, 2# and 3# in Example 1 in [M+H] + The extracted chromatograms have a theoretically accurate molecular weight error within ±10ppm.

[0026] Figure 6 The standard solution in Example 2 (the concentrations of etomidate and propamate are both 50 μg / L) in [M+H] + The extracted chromatograms have a theoretically accurate molecular weight error within ±10ppm. DETAILED DESCRIPTION

[0027] In order to better understand the present invention, the content of the present invention is further explained below in conjunction with the embodiments, but the present invention is not limited to the following embodiments.

[0028] The present invention provides a method for qualitatively and quantitatively analyzing new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight high-resolution mass spectrometry (DPiMS-Q-TOF MS), which specifically comprises the following steps:

[0029] (1) preparing an internal standard solution: mixing ultrapure water and an organic solvent in a volume ratio of 1:1 to 3:1, and then adding a substance having a structure similar to the new psychoactive substance to be tested as an internal standard to obtain an internal standard solution;

[0030] (2) diluting the electronic cigarette oil to be tested by 100 to 1000 times with the internal standard solution to obtain the sample solution to be tested; preparing a standard solution of the standard substance with a concentration ranging from 50 to 5000 μg / L using the internal standard solution; wherein the standard substance is one or more new psychoactive substances, and the standard solution is prepared at least five concentrations;

[0031] (3) analyzing the standard solution prepared in step (2) by in situ ionization-quadrupole time-of-flight high-resolution mass spectrometry to obtain a chromatogram, and then establishing a standard curve for each new psychoactive substance (i.e., target substance) by using the internal standard method, with the concentration of the standard solution as the horizontal axis and the peak area ratio of each new psychoactive substance standard and the internal standard as the vertical axis;

[0032] (4) Under the same detection conditions as step (3), the sample solution to be tested is analyzed by in situ ionization-quadrupole time-of-flight high-resolution mass spectrometry to obtain a chromatogram;

[0033] If the new psychoactive substance to be tested (i.e., the target substance) in the sample solution is in [M+H] + The theoretical accurate molecular weight error is within ±10ppm. No clustered chromatographic peaks can be extracted. The internal standard is in [M+H] + If the clustered chromatographic peaks are extracted within the theoretical accurate molecular weight error of ±10ppm, the sample is considered to have no target substance detected; if the target substance and the internal standard substance in the sample solution are within [M+H] + If the clustered chromatographic peaks are extracted within the theoretical accurate molecular weight error of ±10ppm, it is considered that the target is detected in the sample.

[0034] (5) If the target substance is detected in the sample, the peak area ratio of the target substance and the internal standard is substituted into the standard curve obtained in step (3), the concentration of the new psychoactive substance in the sample solution to be tested is calculated, and then the content of the target new psychoactive substance in the electronic cigarette oil to be tested is converted according to the dilution multiple.

[0035] In the above step (1), the organic solvent is a lower alcohol, preferably methanol, ethanol, isopropanol, and most preferably ethanol; when ultrapure water and the organic solvent are mixed, the volume ratio between the two is 1:1 to 3:1, and most preferably 1:1.

[0036] In the above step (1), the concentration of the internal standard in the internal standard solution is 400-600 μg / L, and the internal standard is a substance or an isotope-labeled substance that is similar in structure to the substance to be tested. For example, lidocaine is selected as the internal standard for detecting etomidate and propamate, and 3,3-dimethyl-2-[1-(5-fluoropentyl) indole-3-carboxamido] butyric acid methyl ester is used as 3,3-dimethyl-2-[1-(5-fluoropentyl) indole-3-carboxamido] butyric acid methyl ester-D3 is used as the internal standard for detecting 3,3-dimethyl-2-[1-(5-fluoropentyl) indole-3-carboxamido] butyric acid methyl ester.

[0037] In the above step (2), the preparation method of the sample solution to be tested is: transfer 990 μL of the internal standard solution into a 1.5 mL sample bottle, add 10 μL of the electronic cigarette oil sample, and shake thoroughly to mix; if the concentration of the new psychoactive substance in the sample solution to be tested exceeds the linear range of the standard curve, continue to dilute it with the internal standard solution to the linear range.

[0038] In the above steps (3) and (4), the specific analysis process is as follows: 10 μL of the standard solution or the sample solution to be tested is transferred onto the spotting plate, the probe is quickly moved up and down to take samples, and the high voltage applied to the probe causes the standard solution or the sample solution to be tested to migrate, and then electrospray is generated from the tip of the probe, and the generated ions enter the mass spectrometer through the desolvation tube.

[0039] In the above steps (3) and (4), the in-situ ionization source conditions are: sampling time 20-40 msec, ionization time 120-200 msec, probe speed 200-300 mm / sec, sampling position 44-48 mm, discharge voltage 2-3.5 kV; Q-TOFMS conditions are: scanning mode Scan (+), scanning range 50-1000 Da, DL temperature 150-350° C., heating module temperature 30-50° C., cycle time 20-200 msec, and acquisition time 0.1-0.5 min.

[0040] In the present invention, the new psychoactive substance standard and internal standard are both commercially available products.

[0041] In the following examples, Shimadzu's quadrupole time-of-flight high-resolution in-situ probe ionization mass spectrometry system DPiMS-Q-TOF was used. The specific configuration was: mass spectrometer LCMS-9050, ion source PESI, LabSolutionsVersion 5.121 & PESI Solution chromatography workstation. The specific analysis conditions are as follows:

[0042] PESI ion source conditions: sampling time 30 msec, ionization time 160 msec, probe speed 250 mm / sec, sampling position 46 mm, discharge voltage 3.5 kV; mass spectrometer conditions: probe electrospray ionization, positive ion mode, DL temperature 250 °C, heating module temperature 50 °C, cycle time 20 msec, scan range 50-1000 Da, acquisition time 0.3 min.

[0043] Example 1

[0044] A method for qualitatively and quantitatively analyzing etomidate and its analogs in tobacco oil by in-situ ionization-quadrupole time-of-flight high-resolution mass spectrometry comprises the following steps:

[0045] (1) preparing an internal standard solution: mixing ultrapure water and ethanol in a volume ratio of 1:1, and then adding internal standard lidocaine to obtain an internal standard solution, wherein the concentration of lidocaine is 500 μg / L;

[0046] (2) Accurately aspirate 10 μL of the electronic cigarette oil sample, dilute it 1000 times with the internal standard solution, and shake it to obtain a sample solution to be tested. In this embodiment, three electronic cigarette oil samples (provided by the Institute of Forensic Science) were prepared to obtain three sample solutions to be tested, which were numbered 1#, 2#, and 3#, respectively.

[0047] Take a commercially available etomidate standard solution and propamate standard solution with a concentration of 1 mg / mL, mix them with the internal standard solution to prepare a mixed standard stock solution with a concentration of 100 mg / L for both, and then dilute them step by step with the internal standard solution to obtain a series of mixed standard solutions with concentrations of 5000 μg / L, 2000 μg / L, 1000 μg / L, 500 μg / L, 200 μg / L, 100 μg / L and 50 μg / L, respectively (the concentration of the mixed standard solution refers to the concentration of the etomidate standard and the propamate standard, and the concentrations of the etomidate standard and the propamate standard in the mixed standard solution are equal), and the concentration of the internal standard is 500 μg / L;

[0048] Table 1. Information of standards and internal standards

[0049]

[0050] (3) The mixed standard solutions prepared in step (2) are analyzed by in situ ionization-quadrupole time-of-flight high-resolution mass spectrometry to obtain chromatograms, and then the concentration of the mixed standard solution is used as the horizontal axis, and the peak area ratio of each new psychoactive substance standard and the internal standard is used as the vertical axis, and the standard curves of each new psychoactive substance (i.e., the target substance) are established by the internal standard method (specifically, the vertical axes of the two standard curves are the peak area ratio of the etomidate standard and lidocaine, and the peak area ratio of the propamate standard and lidocaine, respectively), as shown in FIG. Figure 2 As shown, the linearity is good and the correlation coefficient is greater than 0.995;

[0051] like Figure 1 As shown, the mixed standard solution with a concentration of 50 μg / L extracted a clustered chromatogram within the theoretical accurate molecular weight error of the target compound ±10 ppm.

[0052] (4) Under the same detection conditions as step (3), the sample solution to be tested is analyzed by in situ ionization-quadrupole time-of-flight high-resolution mass spectrometry to obtain a chromatogram;

[0053] like Figure 3 to Figure 5 As shown, in the electronic cigarette oil in the embodiment, etomidate and propamate are in [M+H]+ The chromatogram was extracted within the theoretical accurate molecular weight error of ±10ppm, and the extracted chromatographic peaks were integrated to calculate the total peak area.

[0054] like Figure 3 As shown, the new psychoactive substance to be tested (i.e., the target substance) in the sample is [M+H] + The theoretical accurate molecular weight error was within ±10ppm, and no clustered chromatographic peaks were extracted. The internal standard was extracted into clustered chromatographic peaks within the theoretical accurate molecular weight error of ±10ppm. Therefore, it was considered that the target substances etomidate and propamate were not detected in the sample solution 1# to be tested, and etomidate and propamate were not detected in the electronic cigarette oil sample 1#; Figure 4 and Figure 5 As shown, the target compound and the internal standard are in [M+H] + Clustered chromatographic peaks were extracted within the theoretical accurate molecular weight error of ±10ppm, so the target substances etomidate and propamate were detected in both the sample solutions 2# and 3#.

[0055] The target substance was detected in the sample solutions 2# and 3#, and the peak area ratio of the target substance and the internal standard substance was substituted into the standard curve obtained in step (3) to calculate the concentration of the new psychoactive substance in the sample solutions. The specific results were: the concentrations of etomidate and propamate in the sample solution 2# were 66.7 μg / L and 66.5 μg / L, respectively, and the concentrations of etomidate and propamate in the sample solution 3# were 1205.8 μg / L and 1879.0 μg / L, respectively;

[0056] Then multiply the above concentrations by the dilution factor of 1000 to obtain the content of the target new psychoactive substances in the electronic cigarette oil to be tested. Specifically, the contents of etomidate and propamate in electronic cigarette oil sample 2# are 66.7 mg / L and 66.5 mg / L, respectively, and the contents of etomidate and propamate in electronic cigarette oil sample 3# are 1205.8 mg / L and 1879.0 mg / L, respectively.

[0057] In order to investigate the accuracy and precision of the method for quantitative analysis of new psychoactive substances in electronic cigarette oil provided by the present invention, a spike recovery experiment was conducted. The specific steps are as follows: etomidate and propamate at concentrations of 100 μg / L and 5000 μg / L were added to the blank electronic cigarette oil sample, respectively, and the determination was carried out according to step (3), and the determination was repeated 5 times. The determination results are shown in Table 2.

[0058] Table 2. Results of investigation on spike recovery (n=5, concentration unit: μg / L)

[0059]

[0060] As can be seen from Table 2, the recoveries of etomidate and propamate in the method provided by the present invention are between 84.5% and 100.3%, and the RSD does not exceed 7.64%, indicating that the method for rapidly determining the content of new psychoactive substances in tobacco oil established by the present invention has high accuracy and good reproducibility.

[0061] Example 2

[0062] In order to investigate the effect of the preparation solvent of the internal standard solution on the sensitivity of the detection of new psychoactive substances in electronic cigarette oil, ultrapure water and methanol were mixed in a volume ratio of 1:1 to prepare the internal standard solution. Other conditions were the same as those in Figure 1 The test conditions are consistent. Figure 6 The standard solution in Example 2 (the concentrations of etomidate and propamate are both 50 μg / L) in [M+H] + The chromatogram extracted within the theoretical accurate molecular weight error of ±10 ppm has a lower sensitivity than that of Example 1. Therefore, when the concentration of the new psychoactive substance in the electronic cigarette oil solution to be tested is low, it is preferred that ethanol and water be mixed in equal volumes as the solvent.

[0063] The above is only a preferred embodiment of the present invention. It should be pointed out that a person skilled in the art can make several improvements and changes without departing from the creative concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A method for qualitative and quantitative analysis of new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight mass spectrometry, characterized in that: After the e-cigarette oil sample is diluted with the internal standard solution, a sample solution for injection is obtained, and then in-situ ionization-quadrupole time-of-flight mass spectrometry is used for analysis to obtain chromatograms of the target substance and the internal standard substance; qualitative judgment is made by extracting the chromatographic peaks within the theoretical accurate molecular weight error of the hydrogenation peaks of the target substance and the internal standard substance within the acquisition time range, and then the new psychoactive substances in the e-cigarette oil sample are quantitatively analyzed by the internal standard method in combination with the standard curve; The internal standard solution is prepared by dissolving the internal standard in a mixed solvent of water and an organic solvent, and the internal standard is an analogue or isotope marker of a new psychoactive substance; The in-situ ionization adopts the in-situ probe ionization mass spectrometry system, and the analysis conditions are as follows: the probe sampling time is 20-40 milliseconds, the ionization time is 120-200 milliseconds, the probe speed is 200-300 mm / milliseconds, the probe descending height is 44-48 mm, and the discharge voltage is 2-3.5 kV; the analysis conditions of the quadrupole time-of-flight mass spectrometry are as follows: positive ion full scan mode, the desolvation tube temperature is 150-350°C, the heating temperature is 30-50°C, the cycle time is 20-200 milliseconds, the scanning mass range is 50-1000 Da, and the acquisition time is 0.1-0.5 minutes.

2. The method for qualitative and quantitative analysis of new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight mass spectrometry according to claim 1, characterized in that: New psychoactive substances include etomidate and its analogues, and synthetic cannabinoids.

3. The method for qualitative and quantitative analysis of new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight mass spectrometry according to claim 2, characterized in that: Etomidate and its analogs include isoprenaline, medetomidine, and propamate; synthetic cannabinoids include 3,3-dimethyl-2-[1-(5-fluoropentyl)indole-3-carboxamido]butyric acid methyl ester, 3,3-dimethyl-2-[1-(4-fluorobutyl)indazole-3-carboxamido]butyric acid methyl ester, and N-(1-methyl-1-phenylethyl)-1-(5-fluoropentyl)indazole-3-carboxamide.

4. The method for qualitative and quantitative analysis of new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight mass spectrometry according to claim 2, characterized in that: When detecting etomidate and its analogues in e-cigarette oil, lidocaine is used as the internal standard; when detecting synthetic cannabinoids, 3,3-dimethyl-2-[1-(5-fluoropentyl)indole-3-carboxamido]butyric acid methyl ester-D3 is used as the internal standard.

5. The method for qualitative and quantitative analysis of new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight mass spectrometry according to claim 1, characterized in that: The e-cigarette oil sample was diluted 100 to 1000 times with the internal standard solution, and the concentration of the internal standard solution was 400 to 600 μg / L.

6. The method for qualitative and quantitative analysis of new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight mass spectrometry according to claim 1, characterized in that: The standard solution used to draw the standard curve is prepared from a standard sample and an internal standard solution, and the concentration of the target substance in the standard solution is in the range of 50 to 5000 μg / L.

7. The method for qualitative and quantitative analysis of new psychoactive substances in tobacco oil by in situ ionization-quadrupole time-of-flight mass spectrometry according to claim 1, characterized in that: The mixed solvent used to prepare the internal standard solution is prepared by mixing water and an organic solvent in a volume ratio of 1:1 to 3:1, and the boiling point of the organic solvent is lower than 100°C.

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