Non-targeted pollutant standard substance as well as map database and application thereof

Abstract

The invention discloses a non-targeted pollutant standard substance and an atlas database and application thereof, the standard substance comprises 50-150 pollutant standard substances, the mass-to-charge ratio of the pollutant standard substances is 50-1200, the polarity logKow is-10-16, the ionization mode is ESI < + > / <-> mode, the standard substance contains C, H, O, N, P, S, Cl, Br and F elements and M + H, M-H and M + Na addition ions, and the sum of M + H, M-H and M + Na is less than or equal to 1. M is an organic compound molecule; in addition, the standard substance comprises an isomeride and an isomer. The digital standard substance for the non-targeted pollutant mixed solution has the advantages of high representativeness of chemical components, wide coverage of chemical properties, large pollutant coverage range, wide concentration range, high uniformity, high stability and the like.

Description

Technical Field

[0001] The present invention relates to the field of analytical chemistry, and in particular to a digital standard substance for a non-targeted pollutant mixed solution, a digital standard substance for a non-targeted pollutant mixed solution, and a method for qualitatively detecting pollutants. Background Art

[0002] With the continuous advancement of mass spectrometry technology, non-targeted analysis (NTA) has achieved significant improvements in resolution, sensitivity and accuracy, and has been widely used in the screening of pollutants in the environment and food. However, in practical applications, the comparability and repeatability of non-targeted analysis methods and data are difficult to guarantee, and standard substances play a key role in quality control technology. In non-targeted analysis, since the actual samples are usually chemically complex and unknown, the standard substances used in the quality control technology of non-targeted analysis need to consider the screening principles of many targets to ensure that the complex conditions faced by non-targeted analysis can be simulated.

[0003] Therefore, non-targeted digital mixed solution standard substances need to be studied. Summary of the invention

[0004] The present invention aims to solve at least one of the technical problems existing in the prior art. To this end, one purpose of the present invention is to provide a non-targeted pollutant mixed solution digital standard material, which has the advantages of representative chemical components and wide coverage of chemical properties, large coverage of pollutants, wide concentration range, good uniformity and stability.

[0005] According to one aspect of the present invention, the present invention provides a non-targeted pollutant mixed solution digital standard material. According to an embodiment of the present invention, the standard material includes: 50-150 pollutant standards, wherein the mass-to-charge ratio of the pollutant standard is 50-1200, the polarity logKow is -10-16, and the ionization mode is ESI+ / - mode, and the standard material contains C, H, O, N, P, S, Cl, Br and F elements, and M+H, MH and M+Na addition ions, wherein M is an organic compound molecule; and the standard material includes isomers and isomeric isomers.

[0006] The digital standard substance of the non-targeted pollutant mixed solution according to the embodiment of the present invention has the advantages of representative chemical composition, wide coverage of chemical properties, large pollutant coverage, wide concentration range, good uniformity and stability, etc., and can be used for instrument calibration verification, retention time correction, quantitative calibration prediction, non-targeted analysis method verification, etc. based on chromatography-high-resolution mass spectrometry to ensure the accuracy of non-targeted acquisition and data processing. At the same time, it can also serve as a necessary bridge for data comparison between multiple analysis platforms and other laboratories.

[0007] In addition, the non-target pollutant mixed solution digital reference material according to the above embodiments of the present invention may further have the following additional technical features:

[0008] According to an embodiment of the present invention, the mass-to-charge ratio of the reference material is 95 - 920, preferably 98.95 - 916.53.

[0009] According to an embodiment of the present invention, the polarity logKow of the reference material is -8.08 to 11.51.

[0010] According to an embodiment of the present invention, the reference material includes 2 groups of isomers and 3 groups of allotropes.

[0011] According to an embodiment of the present invention, the peak height span of the pollutant reference standard is 500 times.

[0012] According to an embodiment of the present invention, it includes 80 - 120 kinds of the pollutant reference standards.

[0013] According to an embodiment of the present invention, the types of the pollutant reference standards are selected from at least one of perfluorinated compounds, organophosphates, personal care and pharmaceutical products, environmentally harmful pollutants, packaging harmful pollutants, pesticides, food additives, and mycotoxins.

[0014] According to an embodiment of the present invention, the pollutant reference standards include 25 - 35 kinds of perfluorinated compounds, 12 - 16 kinds of organophosphates, 20 - 30 kinds of personal care and pharmaceutical products, 15 - 20 kinds of environmentally harmful pollutants and packaging harmful pollutants, 5 - 10 kinds of pesticides, 2 - 8 kinds of food additives, and 1 - 5 kinds of mycotoxins.

[0015] According to an embodiment of the present invention, the reference substances include: perfluoro-3-methoxypropionic acid, perfluoroglutaric acid, perfluoroneopentane sulfonic acid, perfluorovaleric acid, perfluorobutylsulfonamide, perfluorobutane sulfonic acid, perfluoro(2-ethoxyethane) sulfonic acid, 2-(perfluorobutyl)-1-ethanesulfonic acid, perfluoroheptanoic acid, perfluorohexane sulfonic acid, 6:2 fluorotelomer sulfonic acid, perfluoroheptanoic acid, perfluoroethylcyclohexane sulfonate, perfluorosebacic acid, perfluorooctane sulfonic acid, perfluorodecanoic acid, perfluoro-3,7-dimethyloctanoic acid, sulfluramid, F-53B, N-ethyl-N-((heptadecafluorooctyl)sulfonyl)glycine, perfluorodecane sulfonate, perfluorododecanoic acid, perfluorotridecanoic acid, perfluorododecane sulfonic acid, perfluorotetradecanoic acid, perfluorohexadecanoic acid, perfluorooctadecanoic acid, trimethyl phosphate, triethyl phosphate, tripropyl phosphate, tributyl phosphate, tris(2-chloroethyl) phosphate, tris(2-chloropropyl) phosphate, triphenyl phosphate, 2-ethylhexyl diphenyl phosphate, tri-o-cresyl phosphate, tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate, tris(2-ethylhexyl) phosphate, 2,2-bis(chloromethyl)-1,3-propanediol bis[bis(2-chloroethyl) phosphate], tris(2,3-dibromopropyl) phosphate, metronidazole purity, furazolidone, sulfadiazine, sulfamethazine, codeine, hydrocodone, enrofloxacin, oxytetracycline, aliskiren, ritonavir, azithromycin, roxithromycin, tilmicosin, tylosin, perchlorate, bisphenol F, 4-n-octylphenol, 4-n-nonylphenol, bisphenol A, bisphenol S solution, butyl benzyl phthalate, bisphenol AF, tetrachlorobisphenol A, tetrabromobisphenol A, methylparaben, L-carnitine, theophylline, propylparaben, 2-isopropylthioxanthone, sucralose, bromopropylate, fipronil, flufenoxuron, indoxacarb, 5-methylmorpholine-3-amino-2-oxazolidinone, cimaterol, nitrodiamide, hexestrol, clenbuterol, ractopamine, zearalenone, zearalenone, cryptocrystalline violet, ethosuximide, 4-butylphenol, p-tert-butylbenzoic acid / butoxymethylepoxyethane, azelaic acid, monobutyl phthalate, monobenzyl phthalate, 4-sec-butyl-2,6-di-tert-butylphenol, dienestrol, perfluoropentane sulfonic acid, florfenicol, 4,8-dioxo-3-H-perfluorononanoic acid, perfluorooctanoic acid, fomesafen, perfluorononanoic acid or acarbose.

[0016] Further, according to another aspect of the present invention, the present invention provides a chromatographic-mass spectrometric database of a digital reference substance for a non-target pollutant mixed solution. According to an embodiment of the present invention, the database is formed by chromatographic and mass spectrometric maps obtained by performing chromatographic-mass spectrometric detection on the aforementioned digital reference substance of the non-target pollutant mixed solution under different chromatographic conditions and different collision energies.

[0017] According to the embodiment database of the present invention, it contains chromatograms and mass spectra of various pollutants under different chromatographic conditions and collision energies. The coverage range of pollutants is wide. Through spectrum comparison, it can be used for qualitative detection of a wide range of pollutants.

[0018] According to the embodiment of the present invention, the detection conditions for chromatographic detection are as follows: chromatographic column: ACOUITY BEH C18 chromatographic column, parameters: 100×2.1 mm, 1.7 μm; flow rate: 0.2 mL / min; column temperature: 35 °C; injection volume: 5 μL.

[0019] According to the embodiment of the present invention, the mobile phase: the mobile phase is selected from one of the following: Mobile phase condition 1: Mobile phase B is methanol, and mobile phase A is deionized water - methanol, concentration: 9:1, v / v; Mobile phase condition 2: Mobile phase B is 0.01% formic acid - methanol, and mobile phase A is 0.01% formic acid - deionized water - methanol, concentration: 9:1, v / v; Mobile phase condition 3: Mobile phase B is 0.01% formic acid + 5 mM ammonium formate - methanol, and mobile phase A is 0.01% formic acid + 5 mM ammonium formate - deionized water - methanol, concentration: 9:1, v / v; Mobile phase condition 4: Mobile phase B is 5 mM ammonium formate - methanol, and mobile phase A is 5 mM ammonium formate - deionized water - methanol, concentration: 9:1, v / v.

[0020] According to the embodiment of the present invention, the detection conditions for mass spectrometry detection are as follows: monitoring mode: positive / negative ion acquisition, FullMS-ddMS 2 scanning mode; collision energy (CE): 10 eV, 20 eV, 30 eV, 40 eV, 50 eV, 60 eV, 70 eV, 80 eV, and a composite collision energy composed of 10 V, 30 V, and 70 eV.

[0021] Furthermore, according to another aspect of the present invention, the present invention provides a method for qualitative detection of pollutants. According to the embodiment of the present invention, the pollutants are subjected to liquid chromatography - high-resolution mass spectrometry detection, and the obtained chromatograms and mass spectra are compared with the retention times under the same chromatographic conditions and the mass spectra under the same collision energy in the digital standard substance chromatogram - spectrum database of the aforementioned non-target pollutant mixed solution, so as to confirm the types of the pollutants. Thus, by comparing the chromatograms and mass spectra of various pollutants under different chromatographic conditions and collision energies, the pollutants to be detected can be qualitatively detected quickly and accurately, and the coverage range of pollutants is wide and the operation is simple.

[0022] Additional aspects and advantages of the present invention will be given in part in the following description, become apparent in part from the following description, or be understood through the practice of the present invention. Description of the Drawings

[0023] The above and / or additional aspects and advantages of the present invention will become apparent and be readily understood from the following description of embodiments in conjunction with the accompanying drawings, wherein:

[0024] Figure 1 Shows a schematic diagram of the proportion of different categories of compounds according to an embodiment of the present invention;

[0025] Figure 2 Shows a schematic diagram of the results of the mass and polarity coverage range of reference substances according to an embodiment of the present invention;

[0026] Figure 3 Shows a schematic diagram of the elemental composition results of compounds according to an embodiment of the present invention;

[0027] Figure 4 Shows a schematic diagram of the peak height distribution results of 100 compounds in a reference substance according to an embodiment of the present invention;

[0028] Figure 5 Shows the chromatograms of TCEP under 4 chromatographic conditions according to an embodiment of the present invention;

[0029] Figure 6 Shows the chromatograms of Roxithromycin under 4 chromatographic conditions according to an embodiment of the present invention;

[0030] Figure 7 Shows the chromatograms of L - caritine under 4 chromatographic conditions according to an embodiment of the present invention;

[0031] Figure 8 Shows the chromatograms of four chromatographic peaks of 6:2 CIPFAES under 4 chromatographic conditions according to an embodiment of the present invention;

[0032] Figure 9 Shows the chromatograms of TCBPA under 4 chromatographic conditions according to an embodiment of the present invention;

[0033] Figure 10 Shows the chromatograms of Zearalenone under 4 chromatographic conditions according to an embodiment of the present invention;

[0034] Figure 11 Shows the chromatograms of Fiproni under 4 chromatographic conditions according to an embodiment of the present invention;

[0035] Figure 12 Shows the first - order mass spectrum of TPHP according to an embodiment of the present invention;

[0036] Figure 13Shows the TPHP secondary mass spectrum according to an embodiment of the present invention, where A: 10 eV spectrum; B: 20 eV spectrum; C: 30 eV spectrum; D: 40 eV spectrum; E: 50 eV spectrum; F: 60 eV spectrum; G: 70 eV spectrum; H: 80 eV spectrum; I: combined spectrum of 10, 30 and 70 eV;

[0037] Figure 14 Shows the PFDA primary mass spectrum according to an embodiment of the present invention;

[0038] Figure 15 Shows the PFDA secondary mass spectrum according to an embodiment of the present invention, where A: 10 eV spectrum; B: 20 eV spectrum; C: 30 eV spectrum; D: 40 eV spectrum; E: 50 eV spectrum; F: 60 eV spectrum; G: 70 eV spectrum; H: 80 eV spectrum; I: combined spectrum of 10, 30 and 70 eV;

[0039] Figure 16 Shows the detected chromatogram of the compound according to an embodiment of the present invention. Detailed implementation manners

[0040] The embodiments of the present invention are described in detail below. The examples of the embodiments are shown in the drawings, where the same or similar reference numerals denote the same or similar elements or elements having the same or similar functions throughout. The embodiments described by referring to the drawings below are exemplary and are only used to explain the present invention and should not be construed as a limitation to the present invention.

[0041] In the description of the present invention, the orientation or positional relationship indicated by the terms "longitudinal", "transverse", "upper", "lower", "front", "rear", "left", "right", "vertical", "horizontal", "top", "bottom", etc. is based on the orientation or positional relationship shown in the drawings, and is only for the convenience of describing the present invention rather than requiring the present invention to be constructed and operated in a specific orientation. Therefore, it should not be construed as a limitation to the present invention.

[0042] It should be noted that the terms "first" and "second" are only used for descriptive purposes and should not be construed as indicating or implying relative importance or implicitly specifying the quantity of the indicated technical features. Thus, the features defined with "first" and "second" may explicitly or implicitly include one or more of such features. Further, in the description of the present invention, unless otherwise specified, the meaning of "plurality" is two or more.

[0043] According to one aspect of the present invention, the present invention provides a digital reference material for a non-target pollutant mixed solution. According to an embodiment of the present invention, the reference material includes: reference standards of 50-150 pollutants, wherein the mass-to-charge ratio of the reference standards of the pollutants is 50-1200, the polar logKow is -10-16, and the ionization mode is the ESI+ / - mode, and the reference material contains elements C, H, O, N, P, S, Cl, Br, and F, as well as M+H, M-H, and M+Na adduct ions, where M is an organic compound molecule; and the reference material includes isomers and allotropes.

[0044] The digital reference material for the non-target pollutant mixed solution according to the embodiment of the present invention has the advantages of representativeness of chemical components, wide coverage of chemical properties, large pollutant coverage range, wide concentration range, good homogeneity and stability, etc. Thus, it can be used for instrument calibration verification, retention time correction, quantitative calibration prediction, non-target analysis method verification, etc. based on chromatography-high resolution mass spectrometry to ensure the accuracy of non-target acquisition and data processing. At the same time, it can also serve as a necessary bridge for data comparison between multiple analysis platforms and other laboratories.

[0045] According to an embodiment of the present invention, the mass-to-charge ratio of the reference material is 95-920, preferably 98.95-916.53. Thus, the mass-to-charge ratio range of the reference material covers the mass-to-charge ratios of common pollutants, and there are compound distributions in each 50 mass-to-charge ratio interval, having good representativeness and being conducive to examining the resolution and mass accuracy of the instrument in different mass-to-charge ratio ranges.

[0046] According to an embodiment of the present invention, the polar logKow of the reference material is -8.08 to 11.51. Thus, this logKow range covers the polarity of common pollutants and is conducive to examining the separation and retention capabilities of liquid chromatography.

[0047] According to an embodiment of the present invention, the reference material includes 2 groups of isomers and 3 groups of allotropes. Thus, it is conducive to fully examining the chromatographic separation ability and the resolution and mass accuracy of the mass spectrometry.

[0048] According to an embodiment of the present invention, the peak height span of the pollutant reference standards is 450-550 times. Thus, this peak height span can cover the response ranges of sufficient compounds and is conducive to examining the sensitivity of the instrument and the repeatability of the instrument under different response intensities.

[0049] According to an embodiment of the present invention, 80-120 of the pollutant reference standards are included. Thus, the range of pollutants included is wide and can cover common pollutants in daily life.

[0050] According to an embodiment of the present invention, the types of the pollutant reference standards are selected from at least one of perfluorinated compounds, organophosphates, personal care and pharmaceutical products, environmentally harmful pollutants, packaging harmful pollutants, pesticides, food additives, and mycotoxins. Thus, the pollutants cover common types of pollutants in the environment and food.

[0051] According to an embodiment of the present invention, the pollutant reference standards include 25 - 35 perfluorinated compounds, 12 - 16 organophosphates, 20 - 30 personal care and pharmaceutical products, 15 - 20 environmentally harmful pollutants and packaging harmful pollutants, 5 - 10 pesticides, 2 - 8 food additives, and 1 - 5 mycotoxins. Thus, the inventor sets the quantity ranges of different types of pollutants according to the abundance of various pollutants in daily life, so that the mixed reference substance can cover common pollutants.

[0052] According to an embodiment of the present invention, the reference substances include: perfluoro-3-methoxypropionic acid, perfluoroglutaric acid, perfluoroneopentane sulfonic acid, perfluorovaleric acid, perfluorobutylsulfonamide, perfluorobutane sulfonic acid, perfluoro(2-ethoxyethane) sulfonic acid, 2-(perfluorobutyl)-1-ethanesulfonic acid, perfluoroheptanoic acid, perfluorohexane sulfonic acid, 6:2 fluorotelomer sulfonic acid, perfluoroheptanoic acid, perfluoroethylcyclohexane sulfonate, perfluorosebacic acid, perfluorooctane sulfonic acid, perfluorodecanoic acid, perfluoro-3,7-dimethyloctanoic acid, sulfluramid, F-53B, N-ethyl-N-((heptadecafluorooctyl)sulfonyl)glycine, perfluorodecane sulfonate, perfluorododecanoic acid, perfluorotridecanoic acid, perfluorododecane sulfonic acid, perfluorotetradecanoic acid, perfluorohexadecanoic acid, perfluorooctadecanoic acid, trimethyl phosphate, triethyl phosphate, tripropyl phosphate, tributyl phosphate, tris(2-chloroethyl) phosphate, tris(2-chloropropyl) phosphate, triphenyl phosphate, 2-ethylhexyl diphenyl phosphate, tri-o-cresyl phosphate, tris(2-butoxyethyl) phosphate, tris(1,3-dichloro-2-propyl) phosphate, tris(2-ethylhexyl) phosphate, 2,2-bis(chloromethyl)-1,3-propanediol bis[bis(2-chloroethyl) phosphate], tris(2,3-dibromopropyl) phosphate, metronidazole purity, furazolidone, sulfadiazine, sulfamethazine, codeine, hydrocodone, enrofloxacin, oxytetracycline, aliskiren, ritonavir, azithromycin, roxithromycin, tilmicosin, tylosin, perchlorate, bisphenol F, 4-n-octylphenol, 4-n-nonylphenol, bisphenol A, bisphenol S solution, butyl benzyl phthalate, bisphenol AF, tetrachlorobisphenol A, tetrabromobisphenol A, methylparaben, L-carnitine, theophylline, propylparaben, 2-isopropylthioxanthone, sucralose, bromopropylate, fipronil, flufenoxuron, indoxacarb, 5-methylmorpholine-3-amino-2-oxazolidinone, cimaterol, dinitolmide, hexestrol, clenbuterol, ractopamine, zearalenone, zearalenone, cryptocrystalline violet, ethosuximide, 4-butylphenol, p-tert-butylbenzoic acid / butoxymethylepoxyethane, azelaic acid, monobutyl phthalate, monobenzyl phthalate, 4-sec-butyl-2,6-di-tert-butylphenol, dienestrol, perfluoropentane sulfonic acid, florfenicol, 4,8-dioxa-3-H-perfluorononanoic acid, perfluorooctanoic acid, fomesafen, perfluorononanoic acid or acarbose.

[0053] Further, according to another aspect of the present invention, the present invention provides a chromatographic-mass spectrometric database of a digital reference substance for a non-target pollutant mixed solution. According to an embodiment of the present invention, the database is formed by chromatographic and mass spectrometric detection of the aforementioned digital reference substance for a non-target pollutant mixed solution under different chromatographic conditions and different collision energies to obtain chromatograms and mass spectra.

[0054] According to the embodiment database of the present invention, it contains the chromatograms and mass spectra of various pollutants under different chromatographic conditions and collision energies. The coverage range of pollutants is wide. Through spectrum comparison, it can be used for the qualitative detection of a wide range of pollutants.

[0055] According to the embodiment of the present invention, the detection conditions for chromatographic detection are as follows: chromatographic column: ACOUITY BEH C18 chromatographic column, parameters: 100×2.1 mm, 1.7 μm; flow rate: 0.2 mL / min; column temperature: 35 °C; injection volume: 5 μL. Thus, the detection sensitivity and accuracy are high.

[0056] According to the embodiment of the present invention, the mobile phase: the mobile phase is selected from one of the following: Mobile phase condition 1: Mobile phase B is methanol, and mobile phase A is deionized water - methanol, concentration: 9:1, v / v; Mobile phase condition 2: Mobile phase B is 0.01% formic acid - methanol, and mobile phase A is 0.01% formic acid - deionized water - methanol, concentration: 9:1, v / v; Mobile phase condition 3: Mobile phase B is 0.01% formic acid + 5 mM ammonium formate - methanol, and mobile phase A is 0.01% formic acid + 5 mM ammonium formate - deionized water - methanol, concentration: 9:1, v / v; Mobile phase condition 4: Mobile phase B is 5 mM ammonium formate - methanol, and mobile phase A is 5 mM ammonium formate - deionized water - methanol, concentration: 9:1, v / v.

[0057] According to the embodiment of the present invention, the detection conditions for mass spectrometry detection are as follows: monitoring mode: positive / negative ion acquisition, FullMS-ddMS 2 Scanning mode; collision energy (CE): 10 eV, 20 eV, 30 eV, 40 eV, 50 eV, 60 eV, 70 eV, 80 eV, and composite collision energies composed of 10 V, 30 V, and 70 eV.

[0058] Furthermore, according to another aspect of the present invention, the present invention provides a method for qualitative detection of pollutants. According to the embodiment of the present invention, the pollutants are subjected to liquid chromatography - high-resolution mass spectrometry detection, and the obtained chromatograms and mass spectra are compared with the retention times under the same chromatographic conditions and the mass spectra under the same collision energies in the digital standard substance chromatogram - spectrum database of the aforementioned non-target pollutant mixed solution, so as to confirm the types of the pollutants. Thus, by comparing the chromatograms and mass spectra of various pollutants under different chromatographic conditions and collision energies, the pollutants to be detected can be qualitatively detected quickly and accurately, and the coverage range of pollutants is wide and the operation is simple.

[0059] Next, the present invention will be described with reference to specific embodiments. It should be noted that these embodiments are merely illustrative and should not be construed as limiting the present invention.

[0060] The solutions of the present invention will be explained below in conjunction with embodiments. Those skilled in the art will understand that the following embodiments are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention. For those embodiments where specific techniques or conditions are not indicated, the techniques or conditions described in the literature in the art or according to the product specifications are followed. The reagents or instruments used without indicating the manufacturer can all be obtained as conventional products through commercial purchase, for example, they can be purchased from Sigma Corporation.

[0061] Example 1

[0062] According to the requirements of the non-target pollutant mixed solution digital reference material of the embodiment of the present invention, the pollutant reference standards are selected. The specific requirements are as follows:

[0063] 1. The principle for selecting reference standard compounds: Using the compound's mass-to-charge ratio, polarity, elemental composition, adduct ions, ionization mode, isomers, allotropes, and compound categories as indicators, characteristic target substances are selected to ensure the representativeness of the chemical composition of the reference material and the wide coverage of chemical properties.

[0064] 2. Coverage of the selected compounds: In the non-target screening of pollutants in the environment and food, the pollutant categories involved include perfluorinated compounds, organophosphorus compounds, personal care and pharmaceutical products, other environmental / package harmful pollutants, pesticides, food additives, and mycotoxins, etc. The mass-to-charge ratio is usually in the range of 50 - 1200, the polarity is mainly in the range of -10 - 16, the elemental composition is mainly C, H, O, N, P, S, Cl, Br, and F, the adduct ions mainly include M+H, M-H, and M+Na, and the ionization mode mainly includes ESI+ / - mode. Thus, 100 compounds are screened within this range to carry out the development of non-target reference materials. The compound categories after screening include 31 perfluorinated compounds, 14 organophosphates, 25 personal care and pharmaceutical products, 17 environmental / package harmful pollutants, 7 pesticides, 4 food additives, and 2 mycotoxins ( Figure 1 ); the mass-to-charge ratio range is 98.97 - 916.53; the polarity range is logKow - 8.08 - 11.51 ( Figure 2 ); the elemental composition includes C, H, O, N, P, S, Cl, Br, and F ( Figure 3 ); the ionization mode mainly includes ESI+ / - mode, 47 compounds in the ESI+ mode, 64 compounds in the ESI- mode, and 11 compounds can be detected in both the ESI+ / - modes. The main adduct ions for the advantage of precursor ion monitoring mainly include [M+H]+, [M+Na]+, and [M-H]-, among which, the adduct ions of 41 compounds are [M+H]+, the adduct ions of 1 compound are [M+Na]+, and the adduct ions of 58 compounds are [M-H]-. In addition, among the 100 compounds, there are also 2 groups of isomers and 3 groups of allotropes.

[0065] 3. Determination of compound concentration: Investigate the ionization efficiency of the target substance to determine its concentration. The ionization efficiency is investigated by detecting the ionization efficiency and response stability of the solution reference material through liquid chromatography coupled with high-resolution mass spectrometry. Finally, the concentration peak height of the target substance is between 1E5 - 5E7 ( Figure 4 ), with a relatively uniform distribution for different peak heights, stable response, and determined by a relative standard deviation RSD of the peak area < 5%.

[0066] 4. Preparation of reference materials: In the gravimetric - volumetric method, a 250 mL volumetric flask is used as the container, and a chromatographic grade methanol solvent is used to prepare the reference materials. After shaking and mixing evenly for multiple times, it is dispensed into 2 mL brown ampoules, 1 mL per bottle, and sealed with a hydrogen - oxygen flame sealing machine. The list of reference materials is shown in Table 7.

[0067] 5. Conduct uniformity and stability tests on the reference materials. The uniformity test includes between - bottle uniformity test and within - bottle uniformity test. The stability test includes short - term stability test and long - term stability test, as follows:

[0068] (1) The instrument method is as follows:

[0069] Analysis is carried out using a Vanquish liquid chromatography - Q Exactive Plus Orbitrap high - resolution mass spectrometer (Thermo). The mass spectrometry detection conditions are as follows:

[0070] ACOUITY BEH C18 chromatographic column (100 mm × 2.1 mm, 1.7 μm); mobile phase: A1 is water - methanol, concentration: 9:1, v / v (5 mM / L ammonium formate + 0.01% formic acid), B1 is methanol (5 mM / L ammonium formate + 0.01% formic acid). A2 is water - methanol, concentration: 9:1, v / v, B2 is methanol; gradient elution program: 0 - 1 min, 1% B; 1 - 5 min, 1% B - 39% B; 5 - 21 min, 39% B - 99% B; 21 - 25 min, 99% B; 25.1 - 30 min, 1% B; flow rate: 0.2 mL / min; column temperature: 30 °C; injection volume: 5 μL. Heated electrospray ionization (HESI), data acquisition mode is Full MS - ddMS2 positive and negative ion simultaneous scanning mode; spray voltage is set at 3 kV, capillary temperature is 320 °C, heating temperature is 350 °C, sheath gas flow rate is 40 Arb, auxiliary gas flow rate is 10 Arb, purge gas flow rate is 2 Arb; for full scan of the first - stage mass spectrometry (Full MS), the mass scan range of the parent ion is m / z 80 - 1200; for the acquisition of the second - stage mass spectrometry, data - dependent acquisition (ddMS2) is used, and ddMS2 selects the top 10 ions with the highest parent ion response for the acquisition of the second - stage mass spectrometry; the first - stage resolution is 70,000, the second - stage resolution is 35,000; the collision energy (NCE) is set at 10, 30 and 70 eV, the automatic gain control for the number of ions entering the orbitrap (AGC target) is 1E6, and the maximum dwell time is 100 ms.

[0071] (2) Test methods and results for homogeneity: Randomly select 11 packages from the developed reference material, and take 2 sub - samples from each package for between - bottle and within - bottle homogeneity tests. The injection volume is 5 μL, and the test is carried out according to the above - mentioned instrument method. The F - test results show that the F - values of all 100 compounds are less than the critical value, there is no significant difference between within - group and between - group, and the sample is homogeneous.

[0072] (3) Stability test methods and results: The stability test includes short-term and long-term stability tests. For the short-term stability of this reference material, it was monitored for 7 days at 4°C. Each time, 2 packages were randomly selected, and 3 sub-samples were taken from each package. For the long-term stability test, the samples were stored at -30°C in the dark. According to the principle of denser monitoring at the beginning and sparser later, the monitoring time was 6 months. Each time, 2 packages were randomly selected, and 3 sub-samples were taken from each package. The trend analysis method was used for the short-term and long-term stability tests of the reference material. Calculate the slope regression coefficient β1 and the standard deviation s(β1) of the slope. t is the critical value of the t-distribution. If |β1| < t·s(β1), there is no obvious trend change. The experimental results showed that for the final 100 compounds, |β1| < t·s(β1), and the samples were stable.

[0073] 6. Establish a liquid chromatography-high resolution mass spectrometry database for reference materials. On the one hand, collect under different chromatographic conditions, and on the other hand, collect precursor ions and product ion spectra. Among them, for the collection of product ion spectra, fragment ion spectra were collected at different collision energies of 10, 20, 30, 40, 50, 60, 70, and 80 eV. Construct a database containing instrument information, instrument parameters, compound information, compound quantity values, chromatographic retention times, precursor ion and fragment ion information, and spectra.

[0074] (1) Chromatographic conditions:

[0075] Chromatographic column: ACOUITY BEH C18 chromatographic column, parameters: 100×2.1 mm, 1.7 μm;

[0076] Flow rate: 0.2 mL / min;

[0077] Column temperature: 35°C;

[0078] Injection volume: 5 μL;

[0079] Mobile phase:

[0080] Mobile phase condition 1: Mobile phase B is methanol, and mobile phase A is deionized water-methanol, concentration: 9:1, v / v.

[0081] Mobile phase condition 2: Mobile phase B is 0.01% formic acid-methanol, and mobile phase A is 0.01% formic acid-deionized water-methanol, concentration: 9:1, v / v.

[0082] Mobile phase condition 3: Mobile phase B is 0.01% formic acid + 5 mM ammonium formate-methanol, and mobile phase A is 0.01% formic acid + 5 mM ammonium formate-deionized water-methanol, concentration: 9:1, v / v.

[0083] Mobile phase condition 4: Mobile phase B is 5 mM ammonium formate - methanol, and mobile phase A is 5 mM ammonium formate - deionized water - methanol, concentration: 9:1, v / v.

[0084] Table 1 Mobile phase gradient:

[0085] Time (min) ％A ％B 0 99 1 1 99 1 5 61 39 21 1 99 25 1 99 25.1 99 1 30 99 1

[0086] (2) Chromatographic detection results of reference substances under different chromatographic conditions

[0087] The retention times of the chromatographic detection of reference substances under different chromatographic conditions are shown in Table 2. Taking TCEP (tris(2-chloroethyl) phosphate), Roxithromycin, and L-carnitine in positive ionization mode as examples, they are respectively as Figure 5 , Figure 6 and Figure 7 shown. Taking 6:2ClPFAES (F-53B), TCBPA (tetrachlorobisphenol A), Zearalenone, and Fipronil in negative ionization mode as examples, they are respectively as Figure 8 , Figure 9 , Figure 10 and Figure 11 shown.

[0088] Table 2 Retention time information of 100 compounds under different chromatographic conditions

[0089]

[0090]

[0091]

[0092]

[0093] (3) Mass spectrometry detection conditions

[0094] Monitoring mode: Positive / negative ion acquisition, Full MS-ddMS2 scan mode;

[0095] Spray voltage: 3 kV;

[0096] Ion source temperature: 350 °C;

[0097] Evaporation temperature: 320 °C;

[0098] Sheath gas flow rate: 40 Arb;

[0099] Auxiliary gas flow rate: 10 Arb;

[0100] Purge gas flow rate: 2 Arb;

[0101] Collision energy (CE): Combinations (10, 30, 70 eV), 10, 20, 30, 40, 50, 60, 70, 80 eV.

[0102] (4) Mass spectrometry detection results

[0103] In the ESI+ mode, taking TPHP (triphenyl phosphate) as an example, the Full mass information is shown in Table 3, and the first-order mass spectrum is as Figure 12 shown, the fragment ion information is shown in Table 4, and the fragment mass spectrum is as Figure 13 shown; taking PFDA (perfluorodecanoic acid) as an example, the Full mass information is shown in Table 5, and the first-order mass spectrum is as Figure 14 shown, the fragment ion information is shown in Table 6, and the fragment mass spectrum is as Figure 15 shown.

[0104] Table 3 Full mass information of TPHP

[0105] m / z Abundance / % 327.07782 100.00 328.08112 19.44 332.11938 3.9 329.08344 2.1

[0106] Table 4 Fragment ion information of TPHP

[0107]

[0108]

[0109] Table 5 Full mass information of PFDA

[0110] m / z Abundance / % 512.95984 100.00 468.97009 38.60 513.96320 10.27 514.96527 0.11

[0111] Table 6 Fragment ion information of PFDA

[0112]

[0113] 7. The solution reference material entity and the database are paired to form a digital new reference material.

[0114] 8. List of compounds in the reference material

[0115] Table 7 List of compounds and concentrations

[0116]

[0117]

[0118]

[0119]

[0120] Example 2

[0121] The reference material prepared in Example 1 was applied to the verification of the untargeted analysis method, where the liquid chromatography conditions were each run once under 2 different conditions.

[0122] 1. Chromatography conditions

[0123] (1) Liquid chromatography condition 1:

[0124] Chromatographic column: ACOUITY BEH C18 chromatographic column, parameters: 100×2.1 mm, 1.7 μm;

[0125] Injection volume: 5 μL;

[0126] Sample temperature: 10 °C;

[0127] Column temperature: 35 °C

[0128] Flow rate: 0.2 mL / min;

[0129] Mobile phase: Phase B is 0.01% formic acid + 5 mM ammonium formate - methanol, Phase A is 0.01% formic acid + 5 mM ammonium formate - deionized water methanol, concentration: 9:1, v / v.

[0130] (2) Liquid chromatography condition 2:

[0131] Chromatographic column: ACOUITY BEH C18 chromatographic column, parameters: 100×2.1 mm, 1.7 μm;

[0132] Injection volume: 5 μL;

[0133] Sample temperature: 10 °C;

[0134] Column temperature: 35 °C

[0135] Flow rate: 0.2 mL / min;

[0136] Mobile phase: Phase B is methanol, Phase A is deionized water methanol, concentration: 9:1, v / v.

[0137] (3) The gradient elution conditions of liquid chromatography are:

[0138] Time (min) Flow rate (mL / min) ％A ％B 0 0.2 99 1 1 0.2 99 1 5 0.2 61 39 21 0.2 1 99 25 0.2 1 99 25.1 0.2 99 1 30 0.2 99 1

[0139] 2. Mass spectrometry conditions:

[0140] Monitoring mode: Positive / negative ion acquisition, Full MS-ddMS2 scan mode;

[0141] Spray voltage: 3 kV;

[0142] Ion source temperature: 350 °C;

[0143] Evaporation temperature: 320 °C;

[0144] Sheath gas flow rate: 40 Arb;

[0145] Auxiliary gas flow rate: 10 Arb;

[0146] Purge gas flow rate: 2 Arb;

[0147] Collision energy (NCE): 10, 30, 70 eV.

[0148] Under the above two non-targeted analysis conditions, 100 compounds in the reference substance prepared in Example 1 can be detected and qualitatively analyzed. The chromatogram is as Figure 16 shown.

[0149] In the description of this specification, the descriptions with reference to terms such as "one embodiment", "some embodiments", "example", "specific example", or "some examples" etc. mean that the specific features, structures, materials, or characteristics described in connection with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials, or characteristics described can be combined in a suitable manner in any one or more embodiments or examples.

[0150] Although the embodiments of the present invention have been shown and described, those of ordinary skill in the art can understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention. The scope of the present invention is defined by the claims and their equivalents.

Claims

1. A digital standard material for a non-targeted pollutant mixed solution, characterized in that: include: 50-150 pollutant standards, The mass-to-charge ratio of the pollutant standard is 50-1200, the polarity logKow is -10-16, and the ionization mode is ESI+ / - mode. Furthermore, the standard substance comprises C, H, O, N, P, S, Cl, Br and F elements, and M+H, MH and M+Na addition ions, wherein M is an organic compound molecule; Furthermore, the standard substance includes isomers and isomeric forms.

2. The standard substance according to claim 1, characterized in that: The mass-to-charge ratio of the standard substance is 95-920, preferably 98.95-916.

53. Optionally, the polarity logKow of the standard substance is -8.08 to 11.51, Optionally, the standard substance includes 2 groups of isomers and 3 groups of allotropes.

3. The standard substance according to claim 1, characterized in that: The peak height span of the contaminant standard is 500 times.

4. The standard substance according to claim 1, characterized in that: It includes 80 to 120 kinds of pollutant standards.

5. The standard substance according to claim 1, characterized in that: The type of the pollutant standard is selected from at least one of perfluorinated compounds, organophosphates, personal care and pharmaceutical products, environmentally harmful pollutants, packaging harmful pollutants, pesticides, food additives and mycotoxins.

6. The standard substance according to claim 1, characterized in that: The pollutant standards include 25-35 perfluorinated compounds, 12-16 organophosphates, 20-30 personal care and pharmaceutical products, 15-20 environmentally hazardous pollutants and packaging hazardous pollutants, 5-10 pesticides, 2-8 food additives and 1-5 mycotoxins.

7. The standard substance according to claim 1, characterized in that: The standard substances include: perfluoro-3-methoxypropionic acid, perfluoroglutaric acid, perfluoroneopropane sulfonic acid, perfluoropentanoic acid, perfluorobutylsulfonamide, perfluorobutane sulfonic acid, perfluoro(2-ethoxyethane)sulfonic acid, 2-(perfluorobutyl)-1-ethanesulfonic acid, perfluoroheptanoic acid, perfluorohexane sulfonic acid, 6:2 fluoroadjustable sulfonic acid, perfluoroheptanoic acid, perfluoroethylcyclohexane sulfonate, perfluorosebacic acid, perfluorooctane sulfonic acid, perfluorodecanoic acid, perfluoro-3,7-dimethyloctanoic acid, sulfluramid, F-53B, N-ethyl-N-((heptadecafluorooctyl)sulfonyl)glycine, perfluorodecane sulfonate, perfluoro Dodecanoic acid, perfluorotridecanoic acid, perfluorododecanesulfonic acid, perfluorotetradecanoic acid, perfluorohexadecanoic acid, perfluorooctadecanoic acid, trimethyl phosphate, triethyl phosphate, tripropyl phosphate, tri-n-butyl phosphate, tri(2-chloroethyl) phosphate, tri(2-chloropropyl) phosphate, triphenyl phosphate, 2-ethylhexyl diphenyl phosphate, tri-o-cresyl phosphate, tri(2-butoxyethyl) phosphate, tri(1,3-dichloro-2-propyl) phosphate, tri(2-ethylhexyl) phosphate, 2,2-bis(chloromethyl)-1,3-propanediol bis[bis(2-chloroethyl) phosphate] , tris(2,3-dibromopropyl) phosphate, metronidazole purity, furazolidone, sulfadiazine, sulfadimethoxine, codeine, hydrocodone, enrofloxacin, oxytetracycline, aliskiren, ritonavir, azithromycin, roxithromycin, tilmicosin, tylosin, perchlorate, bisphenol F, 4-octylphenol, 4-nonylphenol, bisphenol A, bisphenol S solution, butyl benzyl phthalate, bisphenol AF, tetrachlorobisphenol A, tetrabromobisphenol A, methyl paraben, L-carnitine, theophylline, propyl parahydroxybenzoate, 2-isopropylthioxanthone, sucralose, bromopyrine, fipronil, fluorine Fluoxetine, indoxacarb, 5-methylmorpholin-3-amino-2-oxazolidinone, cimaterol, dinitolamide, hexestrol, clenbuterol, ractopamine, zearalenone, zearalenone, leuco crystal violet, ethosuximide, 4-butylphenol, 4-tert-butylbenzoic acid / butoxymethyl oxirane, azelaic acid, monobutyl phthalate, monobenzyl phthalate, 4-sec-butyl-2,6-di-tert-butylphenol, dienestrol, perfluoropentane sulfonic acid, florfenicol, 4,8-dioxa-3-H-perfluorononanoic acid, perfluorooctanoic acid, fomesafen, perfluorononanoic acid, or acarbose.

8. A chromatographic-mass spectrometric database of digital standard substances for non-targeted pollutant mixed solutions, characterized in that: The database is formed by performing chromatography-mass spectrometry detection on the digital standard substance of the non-targeted pollutant mixed solution according to claim 1 under different chromatographic conditions and different collision energies to obtain the chromatogram and mass spectrum.

9. The chromatography-mass spectrometry database according to claim 8, characterized in that: The detection conditions of the chromatographic detection are: Chromatographic column: ACOUITY BEH C18 column, parameters: 100×2.1mm, 1.7μm; Flow rate: 0.2 mL / min; Column temperature: 35°C; Injection volume: 5 μL; Mobile phase: The mobile phase is selected from one of the following: Mobile phase condition 1: Mobile phase B is methanol, phase A is deionized water-methanol, concentration: 9:1, v / v; Mobile phase condition 2: Mobile phase B was 0.01% formic acid-methanol, mobile phase A was 0.01% formic acid-deionized water-methanol, concentration: 9:1, v / v; Mobile phase condition 3: Mobile phase B is 0.01% formic acid + 5 mM ammonium formate-methanol, mobile phase A is 0.01% formic acid + 5 mM ammonium formate-deionized water-methanol, concentration: 9:1, v / v; Mobile phase condition 4: mobile phase B is 5 mM ammonium formate-methanol, mobile phase A is 5 mM ammonium formate-deionized water-methanol, concentration: 9:1, v / v; Optionally, the detection conditions of the mass spectrometry detection are: Monitoring mode: positive / negative ion acquisition, FullMS-ddMS 2 Scan mode; Collision energy (CE): 10 eV, 20 eV, 30 eV, 40 eV, 50 eV, 60 eV, 70 eV, 80 eV, and a composite collision energy consisting of 10 V, 30 V, and 70 eV.

10. A method for qualitative detection of pollutants, characterized in that: The pollutant is subjected to liquid chromatography-high resolution mass spectrometry detection, and the chromatogram and mass spectrum obtained by detection are compared with the retention time of the same chromatographic conditions and the mass spectrum of the same collision energy in the mass chromatography-spectrum database of the digital standard substance of the non-targeted pollutant mixed solution described in claim 8 or 9, so as to confirm the type of the pollutant.

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