Establishment and application methods, devices and equipment of glucocorticoid mass spectrometry database

Abstract

The invention belongs to the technical field of cosmetics detection, and discloses a method, device and equipment for automatically establishing a glucocorticoid mass spectrum database. The method comprises: obtaining simplified molecular linear input standard texts of several glucocorticoid compounds, converting them into molecular structures, adding hydrogen ions to obtain the mass-to-charge ratio of parent ions; searching for target specific groups for simulated fracture according to specific sequences, and calculating the mass-to-charge ratio of characteristic fragment ions; wherein the target specific groups are part or all of a plurality of preset specific fracture groups, summarizing the mass-to-charge ratio of parent ions and the mass-to-charge ratio of each characteristic fragment ion to obtain a simulated mass spectrum, and arranging them into csv files in the TraceFinder database format to form a glucocorticoid mass spectrum database, which can expand the coverage of the database to 7199 kinds; and disclosing a quasi-targeted screening method for glucocorticoids in cosmetics based on the database, realizing accurate screening of glucocorticoids from a large amount of sample mass spectrum data collected, and improving screening efficiency and accuracy.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics testing, and specifically relates to a method, device, equipment, and storage medium for establishing and applying a glucocorticoid mass spectrometry database. Background Art

[0002] In recent years, the problem of illegal additives in cosmetics has continued to attract the attention of consumers and market regulators. Illegal additions of glucocorticoids (GCs) are prone to occur in freckle removal, whitening cosmetics and facial masks. When such cosmetics are used in the early stage, the skin feels whitening quickly and delicate, but long-term continuous use can lead to local side effects such as skin vasodilation, hormone-dependent dermatitis and irreversible skin atrophy, and can even cause serious systemic damage such as osteoporosis, hypertension and diabetes. Therefore, relevant regulations expressly prohibit the addition of glucocorticoids in cosmetics. Glucocorticoids have pharmacological effects such as anti-inflammatory and immunosuppression, and are generally used to treat allergic and inflammatory diseases. Depending on the combination of different groups and the different spatial configurations, the number of glucocorticoid compounds can reach tens of thousands, and the large number poses a huge challenge to detection technology and market supervision.

[0003] At present, the traditional detection methods for glucocorticoids mainly include thin layer chromatography (TLC), gas chromatography-mass spectrometry, high performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS / MS), liquid chromatography-high resolution mass spectrometry, etc. Traditional detection methods usually use standard substances for the qualitative and quantitative analysis of known glucocorticoids, with limited coverage, and it is difficult to detect unknown glucocorticoid components. Summary of the invention

[0004] The purpose of the present invention is to provide a method, device, equipment, and storage medium for establishing and applying a glucocorticoid mass spectrometry database, which can expand the coverage of glucocorticoids and thus improve the accuracy of screening results.

[0005] The first aspect of the present invention discloses a method for establishing a glucocorticoid mass spectrum database, wherein the method for establishing a mass spectrum database is executed by a computer device, wherein the computer device is provided with an executable program code, and the computer device calls the executable program code to execute the method for establishing the mass spectrum database; the method for establishing the mass spectrum database comprises:

[0006] The computer device obtains simplified molecular linear input specification texts of several sample objects, wherein the sample objects are glucocorticoid compounds and / or derivatives of glucocorticoid compounds;

[0007] The computer device converts the simplified molecular linear input specification text of each sample object into a molecular structure;

[0008] The computer device adds hydrogen ions to the molecular structure to obtain positively charged molecular ions as parent ions, and calculates the mass-to-charge ratio of the parent ions;

[0009] The computer device searches for the target specific group in the parent ion structure according to the specific sequence, simulates the breakage of the target specific group in sequence, and calculates the mass-to-charge ratio of the characteristic fragment ion obtained after each breakage; wherein the target specific group is part or all of the preset multiple specific breakage groups, and the multiple specific breakage groups include -F on the ring at the adjacent position of C=C, dihydrooxazolyl, -OH on the ring, -OH, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the non-ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring with a carbon number of <5, -F on the ring not at the adjacent position of C=C, alkanoyloxy on the non-ring with a carbon number of <6, phosphate, oxazolidinyl, -Cl on the ring, alkoxy on the ring, -Br on the ring, and carbonylmethyl carbon cation;

[0010] The computer device summarizes the mass-to-charge ratio of the parent ion and the mass-to-charge ratio of each characteristic fragment ion to obtain a simulated mass spectrum of each sample object;

[0011] The computer device organizes the simulated mass spectra of each sample object into a csv file according to the TraceFinder database format to form a glucocorticoid mass spectrum database.

[0012] The second aspect of the present invention discloses a quasi-targeted screening method for glucocorticoids in cosmetics, using the glucocorticoid mass spectrometry database described in the first aspect, the quasi-targeted screening method is performed by a computer device, the computer device is provided with a controller and a data storage device connected to a liquid chromatography high-resolution mass spectrometer, and the computer device is installed with TraceFinder software for performing the quasi-targeted screening method; the quasi-targeted screening method comprises:

[0013] The computer device acquires mass spectrum data of the sample to be tested;

[0014] The computer device performs chromatographic peak extraction on the mass spectrum data of the sample to be tested to obtain a primary mass spectrum peak and a secondary mass spectrum peak;

[0015] The computer device matches the primary mass spectrum peak with the parent ion in the glucocorticoid mass spectrum database, and calculates the parent ion mass error and isotope distribution matching degree;

[0016] If the parent ion mass error is less than the specified error and the isotope distribution matching degree is greater than the specified matching degree, the computer device matches the secondary mass spectrum peak with the fragment ions in the glucocorticoid mass spectrum database to obtain a matching result.

[0017] The third aspect of the present invention discloses a device for establishing a glucocorticoid mass spectrometry database, comprising:

[0018] A text acquisition unit, used to acquire simplified molecular linear input specification texts of several sample objects, wherein the sample objects are glucocorticoid compounds and / or derivatives of glucocorticoid compounds;

[0019] A conversion unit, used for converting the simplified molecular linear input specification text of each sample object into a molecular structure;

[0020] The simulated ionization unit is used to add hydrogen ions to the molecular structure to obtain positively charged molecular ions as parent ions and calculate the mass-to-charge ratio of the parent ions;

[0021] A simulated fracture unit is used to search for target specific groups in the parent ion structure according to a specific sequence, simulate the fracture of the target specific groups in sequence, and calculate the mass-to-charge ratio of the characteristic fragment ions obtained after each fracture; wherein the target specific group is part or all of the preset multiple specific fracture groups, and the multiple specific fracture groups include -F on the ring at the adjacent position of C=C, dihydrooxazolyl, -OH on the ring, -OH, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring with a carbon number of <5, -F on the ring not at the adjacent position of C=C, alkanoyloxy on the ring with a carbon number of <6, phosphate, oxazolidinyl, -Cl on the ring, alkoxy on the ring, -Br on the ring, and carbonylmethyl carbon cation;

[0022] A summary unit is used to summarize the mass-to-charge ratio of the parent ion and the mass-to-charge ratio of each characteristic fragment ion to obtain a simulated mass spectrum of each sample object;

[0023] The sorting unit is used to sort the simulated mass spectrum of each sample object into a csv file according to the TraceFinder database format to form a glucocorticoid mass spectrum database.

[0024] The fourth aspect of the present invention discloses a quasi-targeted screening device for glucocorticoids in cosmetics, using the glucocorticoid mass spectrometry database described in the third aspect, and the quasi-targeted screening device comprises:

[0025] A data acquisition unit, used to acquire mass spectrum data of the sample to be tested;

[0026] An extraction unit is used to perform chromatographic peak extraction on the mass spectrum data of the sample to be tested to obtain a primary mass spectrum peak and a secondary mass spectrum peak;

[0027] The first matching unit is used to match the primary mass spectrum peak with the parent ion in the glucocorticoid mass spectrum database, and calculate the parent ion mass error and isotope distribution matching degree;

[0028] The second matching unit is used to match the secondary mass spectrum peak with the fragment ions in the glucocorticoid mass spectrum database to obtain a matching result when the mother ion mass error is less than the specified error and the isotope distribution matching degree is greater than the specified matching degree.

[0029] The fifth aspect of the present invention discloses a computer device, comprising a memory storing executable program code and a processor coupled to the memory; the processor calls the executable program code stored in the memory to execute the method for establishing a glucocorticoid mass spectrometry database disclosed in the first aspect.

[0030] The sixth aspect of the present invention discloses a computer-readable storage medium, which stores a computer program, wherein the computer program enables a computer to execute the method for establishing a glucocorticoid mass spectrometry database disclosed in the first aspect.

[0031] The beneficial effects of the present invention include:

[0032] (1) Glucocorticoids have the same cyclopentaphenanthrene nucleus structure, and their mass spectrometry fragmentation specificity is relatively strong. Based on the research and analysis of several glucocorticoid secondary mass spectra, the present invention summarizes the glucocorticoid-specific mass spectrometry fragmentation law, and independently develops a glucocorticoid-specific mass spectrometry fragmentation algorithm program using computer programming technology, thereby realizing the automated establishment of a glucocorticoid mass spectrometry database and the application of a screening method.

[0033] (2) The present invention can automatically simulate the mass spectrometry fragmentation process of glucocorticoids and generate characteristic glucocorticoid fragment ions in batches in a one-click manner. At the same time, with the help of the large-scale chemical substance database on the Internet, the number of glucocorticoid compounds has been expanded to 7,199, and their structures represent almost all available glucocorticoids and their derivatives, thereby increasing the coverage of the screening.

[0034] (3) The present invention uses the developed mass spectrometry fragmentation algorithm program to simulate the fragmentation of glucocorticoid compounds, constructs a large-scale glucocorticoid mass spectrometry database, uses ultra-high performance liquid chromatography-quadrupole-electrostatic field orbital ion trap mass spectrometry (UHPLC-Q-Orbitrap MS) to collect data, uses TraceFinder software to process data, and establishes a glucocorticoid quasi-targeted screening and analysis technology. This technology can accurately screen out glucocorticoids and their derivatives in massive high-resolution mass spectrometry data.

[0035] (4) Compared with the existing methods, the present invention greatly improves the coverage of glucocorticoid compounds, and the constructed glucocorticoid mass spectrometry database is used for rapid screening and identification of glucocorticoids in cosmetics. The present invention sets the parameters of parent ion mass error <5ppm, isotope distribution match>90%, secondary fragment mass error <5ppm, and number of matches ≥2, reaching 7 identification points, which is much larger than the regulatory requirement of at least 4 identification points (IPs), greatly improving the recognition accuracy. The method can directly output the screening results, greatly reduce manual intervention, reduce the difficulty and time investment of analysis, and greatly improve the screening efficiency and accuracy. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] The accompanying drawings herein show specific examples of the technical solutions described in the present invention, and together with the specific implementation methods, constitute a part of the specification, and are used to explain the technical solutions, principles and effects of the present invention.

[0037] Unless otherwise specified or defined, the same reference numerals in different drawings represent the same or similar technical features, and the same or similar technical features may also be represented by different reference numerals.

[0038] Figure 1 It is a flow chart of a method for establishing a glucocorticoid mass spectrometry database disclosed in the present invention;

[0039] Figure 2 is a schematic diagram of the chemical structure of the glucocorticoid disclosed in the present invention;

[0040] Figure 3 The present invention discloses Figure 1 Detailed execution flow chart of step 140;

[0041] Figure 4 It is a flow chart of a quasi-targeted screening method for glucocorticoids in cosmetics disclosed in the present invention;

[0042] Figure 5 It is a structural schematic diagram of a device for establishing a glucocorticoid mass spectrometry database disclosed in the present invention;

[0043] Figure 6 It is a schematic structural diagram of a quasi-targeted screening device for glucocorticoids in cosmetics disclosed in the present invention;

[0044] Figure 7 It is a structural schematic diagram of a computer device disclosed in the present invention.

[0045] Description of reference numerals:

[0046] 401, text acquisition unit; 402, conversion unit; 403, simulated ionization unit; 404, simulated fracture unit; 405, summary unit; 406, sorting unit; 501, data acquisition unit; 502, extraction unit; 503, first matching unit; 504, second matching unit; 601, memory; 602, processor. DETAILED DESCRIPTION

[0047] Unless otherwise specified or defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art. In the case of combining the technical solution of the present invention with realistic scenarios, all technical and scientific terms used herein may also have meanings corresponding to the purpose of implementing the technical solution of the present invention. The "first, second..." used herein is only used to distinguish the names and does not represent a specific quantity or order. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0048] It should be noted that when a component is considered to be "fixed to" another component, it can be directly fixed to the other component or there can be a central component; when an component is considered to be "connected to" another component, it can be directly connected to the other component or there can be a central component at the same time; when an component is considered to be "installed on" another component, it can be directly installed on the other component or there can be a central component at the same time. When an component is considered to be "set on" another component, it can be directly set on the other component or there can be a central component at the same time.

[0049] Unless otherwise specified or defined, the "said" and "the" used in this document refer to the technical features or technical contents mentioned or described before the corresponding position, and the technical features or technical contents may be the same as or similar to the technical features or technical contents mentioned therein. In addition, the terms "including" and "having" and any variations thereof used in this document are intended to cover non-exclusive inclusions. For example, a process, method, system, product or device that includes a series of steps or units is not limited to the listed steps or units, but may optionally include steps or units that are not listed, or may optionally include other steps or units inherent to these processes, methods, products or devices.

[0050] The embodiment of the present invention discloses a method for establishing a glucocorticoid mass spectrum database, which is automatically established by computer programming. The execution subject of the method is a computer device, or a device for establishing a glucocorticoid mass spectrum database embedded in a computer device, and the present invention is not limited to this. In order to facilitate understanding of the present invention, the following will be a more detailed description of the specific embodiments of the present invention with reference to the accompanying drawings of the specification taking the computer device as the execution subject. Among them, the computer device is provided with an executable program code, and the computer device calls the executable program code to execute the method for establishing the mass spectrum database.

[0051] like Figure 1 As shown, the method for establishing the mass spectrum database includes the following steps 110 to 160:

[0052] 110. A computer device obtains simplified molecular linear input specification texts of several sample objects, wherein the sample objects are glucocorticoid compounds and / or derivatives of glucocorticoid compounds.

[0053] Among them, the sample object can be to expand the scope of glucocorticoids and their derivatives with the help of large-scale chemical substance databases on the Internet, covering almost all available glucocorticoid compounds. Exemplarily, 100 glucocorticoid compounds are used as the parent core structure, and the large-scale Internet compound database PubChem is used as the data source. Glucocorticoids and their derivatives are obtained by structural similarity matching, and the list is downloaded, duplications and structural confirmations are removed, and enantiomers are merged, and finally 7199 glucocorticoids and their derivatives covering almost all available ones are obtained.

[0054] 120. The computer device converts the simplified molecular linear input specification text of each sample object into a molecular structure.

[0055] The structural information of the glucocorticoid compound to be fragmented is input in the simplified molecular input line entry specification (SMILES) text, and converted into a computer-recognizable molecular structure mol by a computer device. Among them, the glucocorticoid structure is as follows Figure 2 shown.

[0056] 130. The computer equipment adds hydrogen ions to the molecular structure to obtain positively charged molecular ions as parent ions and calculates the mass-to-charge ratio of the parent ions.

[0057] In this step, in order to simulate ESI + Ionization, computer equipment adds H to the molecular structure +In order to obtain the glucocorticoid molecular ion, the glucocorticoid molecular ion is used as the glucocorticoid parent ion, and the mass-to-charge ratio m / z of the parent ion can be calculated and output.

[0058] 140. The computer equipment searches for the target specific groups in the parent ion structure according to a specific sequence, simulates the breakage of the target specific groups in sequence, and calculates the mass-to-charge ratio of the characteristic fragment ions obtained after each breakage.

[0059] It should be noted that the target specific group may be one or more, and may be part or all of the preset multiple specific cleavage groups. The preset multiple specific cleavage groups can be summarized based on the molecular structure of the glucocorticoid compound and its corresponding secondary mass spectrometry data to summarize the glucocorticoid specific cleavage groups and their cleavage processes. The preset multiple specific cleavage groups may include -F on the ring at the C=C adjacent position, dihydrooxazolyl, -OH on the ring, -OH, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the non-ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring with a carbon number of <5, -F on the ring at a non-C=C adjacent position, alkanoyloxy on the non-ring with a carbon number of <6, phosphate, oxazolidinyl, -Cl on the ring, alkoxy on the ring, -Br on the ring, and carbonylmethyl carbon cation. Exemplary, the 16 groups shown in Table 1 below are included:

[0060] Table 1 Glucocorticoid-specific cleavage groups and their cleavage processes

[0061]

[0062]

[0063]

[0064]

[0065] Since glucocorticoid molecules are present in ESI + After ionization at the ion source, positively charged quasi-molecular ions are formed. Quasi-molecular ions are subjected to collisions with 10-30 NCE energy in the high-energy collision cell to produce fragmentation. After studying the fragmentation process, it was found that if the glucocorticoid molecule has 16 groups in Table 1, it will be broken according to the fragmentation process in the table. When two or more groups appear, the fragmentation of different groups will have a certain order, which is related to the molecular structure.

[0066] The multiple preset specific cleavage groups in Table 1 can be combined into three cleavage sequences, each of which includes multiple specific cleavage groups and their cleavage order, such as the first cleavage sequence A, the second cleavage sequence B and the third cleavage sequence C. The first cleavage sequence A is {dihydrooxazolyl, -OH on the ring, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring, -F on the ring that is not adjacent to C=C}; the second cleavage sequence B is {-F, dihydrooxazolyl, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring, -F on the ring that is not adjacent to C=C, -OH on the ring}; the third cleavage sequence C is {alkanoyloxy on the ring, phosphate, oxazolidinyl, alkanoyloxy on the ring, -Cl on the ring, alkoxy on the ring, -OH, -Br on the ring, -OH, carbonylmethyl carbon cation}.

[0067] Therefore, the specific sequence can be a combination of the first cleavage sequence and the third cleavage sequence, or the specific sequence can also be a combination of the second cleavage sequence and the third cleavage sequence. In step 140, it can be first determined whether the specific cleavage group -F appears on the C=C adjacent ring of the parent ion structure; if the specific cleavage group -F does not appear on the C=C adjacent ring, the specific sequence of the combination of the first cleavage sequence A and the third cleavage sequence C is used; if the specific cleavage group -F appears on the C=C adjacent ring, the specific sequence of the combination of the second cleavage sequence B and the third cleavage sequence C is used.

[0068] It should be noted that the priority of the first cleavage sequence A is higher than that of the third cleavage sequence C, and the priority of the second cleavage sequence B is higher than that of the third cleavage sequence C. That is to say, if there is no specific cleavage group -F on the ring adjacent to C=C, the specific sequence is {dihydrooxazolyl, -OH on the ring, alkanoyloxy on the ring with a carbon number ≥5, alkanoyloxy on a non-ring with a carbon number ≥6, acetal, alkanoyloxy on the ring, -F on the ring adjacent to non-C=C, alkanoyloxy on the ring, phosphate, oxazolidinyl, alkanoyloxy on a non-ring, -Cl on the ring, alkoxy on the ring, -OH, -Br on the ring, -OH, carbonylmethyl carbonium ion}; if C= If a specific breaking group -F appears on the ring at the C-adjacent position, the specific sequence is {-F on the ring at the C=C-adjacent position, dihydrooxazolyl, alkanoyloxy on the ring with ≥5 carbon atoms, alkanoyloxy on a non-ring with ≥6 carbon atoms, acetal, alkanoyloxy on the ring, -F on the ring not at the C=C-adjacent position, -OH on the ring, alkanoyloxy on the ring, phosphate, oxazolidinyl, alkanoyloxy on a non-ring, -Cl on the ring, alkoxy on the ring, -OH, -Br on the ring, -OH, carbonylmethyl carbonium ion}.

[0069] When searching for the target specific group according to the specific sequence, each preset specific cleavage group in the specific sequence is traversed, and the same target specific group is searched in the molecular structure in turn. Whenever a target specific group is found in the molecular structure, simulated cleavage is performed. This is performed in turn until all the specific cleavage groups in the specific sequence are traversed. Specifically, the execution flow of step 140 can be as follows: Figure 3 As shown. Figure 3 Search sequentially. If the groups in Table 1 exist, simulate the fracture according to their fracture process, that is, break the chemical bonds, lose the corresponding groups, and calculate the m / z of the fragment ions after the fracture. After the fracture, continue the operation of group search -> group fracture -> output fragments until all groups are found.

[0070] The computer device summarizes the mass-to-charge ratio of the parent ion and the mass-to-charge ratio of each characteristic fragment ion to obtain a simulated mass spectrum of each sample object.

[0071] 160. The computer device organizes the simulated mass spectrum of each sample object into a csv file according to the TraceFinder database format to form a glucocorticoid mass spectrum database.

[0072] Among them, the csv file is a table with the ID of each sample object, simplified molecular linear input specification text, parent ion and characteristic fragment ion m / z. It should be noted that in the subsequent data analysis method, the glucocorticoid mass spectrometry database plays a decisive role in the matching results. The more glucocorticoid compounds contained in the glucocorticoid mass spectrometry database, the wider the screening range, which can improve the accuracy of the screening results. In order to realize the automation of glucocorticoid screening, the glucocorticoid mass spectrometry database was imported into the TraceFinder 4.1 software in a specific format to realize the automated screening of actual sample data.

[0073] In summary, the embodiments of the present invention achieve large-scale expansion of the glucocorticoid mass spectrometry database by summarizing the specific mass spectrometry fragmentation rules of glucocorticoid compounds, thereby greatly improving the screening coverage of glucocorticoid compounds in cosmetics.

[0074] like Figure 4 As shown, the embodiment of the present invention also discloses a quasi-targeted screening method for glucocorticoids in cosmetics, using the glucocorticoid mass spectrometry database constructed in the above embodiment, the quasi-targeted screening method for glucocorticoids in cosmetics is executed by a computer device, the computer device is provided with a controller and a data storage device connected to a liquid chromatography high-resolution mass spectrometer, and the computer device is installed with TraceFinder software for executing the quasi-targeted screening method; the quasi-targeted screening method includes the following steps 310-330:

[0075] 310. The computer device obtains the mass spectrum data of the sample to be tested, and performs chromatographic peak extraction on the mass spectrum data of the sample to be tested to obtain the primary mass spectrum peak and the secondary mass spectrum peak.

[0076] Specifically, a Hypersil Gold C18 column (50 mm × 2.1 mm, 1.9 μm) was selected as an ultra-high performance liquid chromatography column. The gradient elution program was adjusted according to the column adaptation. Under this chromatographic condition, 100 glucocorticoid compounds were effectively separated, and the peak shape was symmetrical. This method set a 2-min 100% acetonitrile elution for unknown glucocorticoid compounds that may have a large logP value, which can effectively elute most glucocorticoid compounds.

[0077] Using ESI + mode, further set the resolution of primary to 70000, secondary to 17500, mass scanning range m / z 200-1500, and three different normalized collision energies (NCE) of 10, 20 and 35 for post-collision superposition. Under this mass spectrometry condition, most of the glucocorticoid compounds have a certain response and can normally collect the primary mass spectrum peak and the secondary mass spectrum peak.

[0078] 320. The computer equipment matches the primary mass spectrum peak with the parent ion in the glucocorticoid mass spectrum database and calculates the parent ion mass error and isotope distribution matching degree.

[0079] Specifically, the method in which the computer device calculates the parent ion mass error in step 320 may be:

[0080] The computer device matches the primary mass spectrum peak with the parent ion in the glucocorticoid mass spectrum database, and then calculates the parent ion mass error based on the measured mass-to-charge ratio of the ion and the theoretical mass-to-charge ratio of the ion. For example, it is calculated by the following formula (1):

[0081]

[0082] Where E represents the parent ion mass error, m c represents the measured mass-to-charge ratio of the ion, and m0 represents the theoretical mass-to-charge ratio of the ion.

[0083] In step 320, the computer device may calculate the isotope distribution matching degree in the following manner:

[0084] The computer device matches the primary mass spectrum peak with the parent ion in the glucocorticoid mass spectrum database, calculates the similarity between the measured intensity of multiple isotope mass spectrum peaks and the theoretical intensity of the corresponding isotope mass spectrum peaks, and determines the similarity as the isotope distribution matching degree. Preferably, multiple isotope mass spectrum peaks with measured intensity > 2% can be selected for calculation.

[0085] For example, it can be calculated by the following formula (2):

[0086]

[0087] Wherein, MA represents the isotope distribution matching degree, Mi represents the measured intensity of the ith isotope mass spectrum peak, Ti represents the theoretical intensity of the ith isotope mass spectrum peak, and n represents the total number of isotope mass spectrum peaks.

[0088] 330. If the parent ion mass error is less than the specified error and the isotope distribution match is greater than the specified match, the computer device matches the secondary mass spectrum peak with the fragment ions in the glucocorticoid mass spectrum database to obtain a matching result.

[0089] For example, if the parent ion mass error is <5ppm and the isotope distribution match is >90%, the primary mass spectrum peak match is determined to be successful. After the primary mass spectrum peak match is passed, the match is automatically run according to the set parameters (secondary fragment mass error <5ppm, matching number ≥2). If the secondary fragment mass error is <5ppm, it means that the fragment match is successful. If the matching number is ≥2, it means that the secondary mass spectrum peak matches the compound in the database successfully. The more successful secondary fragment matches are, the higher the accuracy is. Finally, the matched compounds in the database are output as matching results.

[0090] In summary, this method uses the software TraceFinder 4.1, sets the parameters of parent ion mass error <5ppm, isotope distribution match >90%, secondary fragment mass error <5ppm, number of matches ≥2, reaches 7 identification points, far more than the regulatory requirement of at least 4 identification points (IPs), greatly improving the accuracy of identification. This method can directly output the screening results, greatly reducing manual intervention, reducing the difficulty and time investment of analysis, and greatly improving the screening efficiency and accuracy.

[0091] The quasi-targeted screening method established by the present invention was used to screen glucocorticoids in 955 batches of circulating cosmetics, and 12 batches of positive samples were detected (see Table 2), involving a total of 10 glucocorticoids. Among them, 6 are common glucocorticoids, with a content of 6.1mg / kg to 16.2mg / kg. In addition, the bolded ones are new glucocorticoids that were screened out for the first time in actual samples on the market, with a content of 5.4mg / kg to 28.6mg / kg. Relevant departments should strengthen supervision on the illegal addition of these new glucocorticoids. The results show that this method is applied to the large-scale rapid screening of glucocorticoids in cosmetics, and has very large technical advantages in terms of screening coverage, accuracy and degree of automation, and has broad application prospects.

[0092] Table 2 Actual sample screening positive results

[0093]

[0094] The quasi-targeted screening method established by the present invention was used to screen and analyze the actual cosmetic samples. The screening results showed the extracted ion current chromatogram and the matching of each part, among which fluocinolone acetonide showed the parent ion [C 21 H 26 F2O6+H] + (m / z 413.1770, error-1.59ppm), the parent ion isotope matching score is 100%, the parent ion isotope distribution mass spectrum peak matches all 5, the secondary mass spectrum peak matches 5, and the displayed results are all matched. Combined with its fragmentation law, the fragment m / z393.1708, error-3.86ppm is [M+H] + Neutral loss of HF from the parent ion to obtain [M+H-HF] + Fragment ion; fragment m / z 373.1646, error -0.05ppm is [M+H-HF] + The ion continues to lose HF in a neutral state to obtain [M+H-2HF] + Fragment ions; H2O (fragment m / z 355.1540, error -3.12ppm), (fragment m / z 337.1434, error 1.61ppm), (fragment m / z 319.1329, error 0.01ppm) continued to be lost. The results matched 1 parent ion and 5 secondary fragments. The identification points = 2 + 2.5 * 5 = 14.5, that is, a total of 14.5 identification points were reached, which is much greater than the 4 identification points required by the regulations. At the same time, the screening results are consistent with the confirmation results of the reference substance, indicating that this method has the characteristics of high accuracy and high degree of automation, can automatically match and obtain correct results, and covers a wide range of compounds.

[0095] like Figure 5 As shown, the embodiment of the present invention discloses a device for establishing a glucocorticoid mass spectrum database, including a text acquisition unit 401, a conversion unit 402, a simulated ionization unit 403, a simulated fracture unit 404, a summary unit 405, and a sorting unit 406, wherein:

[0096] A text acquisition unit 401 is used to acquire simplified molecular linear input specification texts of several sample objects, wherein the sample objects are glucocorticoid compounds and / or derivatives of glucocorticoid compounds;

[0097] A conversion unit 402, used to convert the simplified molecular linear input specification text of each sample object into a molecular structure;

[0098] The simulated ionization unit 403 is used to add hydrogen ions to the molecular structure to obtain positively charged molecular ions as parent ions and calculate the mass-to-charge ratio of the parent ions;

[0099] The simulated fracture unit 404 is used to search for target specific groups in the parent ion structure according to a specific sequence, simulate the fracture of the target specific groups in sequence, and calculate the mass-to-charge ratio of the characteristic fragment ions obtained after each fracture; wherein the target specific groups are part or all of the preset multiple specific fracture groups, and the multiple specific fracture groups include -F on the ring at the adjacent position of C=C, dihydrooxazolyl, -OH on the ring, -OH, alkanoyloxy on the ring with a carbon number ≥5, alkanoyloxy on the non-ring with a carbon number ≥6, acetal, alkanoyloxy on the ring with a carbon number <5, -F on the ring not at the adjacent position of C=C, alkanoyloxy on the non-ring with a carbon number <6, phosphate, oxazolidinyl, -Cl on the ring, alkoxy on the ring, -Br on the ring, and carbonylmethyl carbon cation.

[0100] A summarizing unit 405 is used to summarize the mass-to-charge ratio of the parent ion and the mass-to-charge ratio of each characteristic fragment ion to obtain a simulated mass spectrum of each sample object;

[0101] The sorting unit 406 is used to sort the simulated mass spectra of each sample object into a csv file according to the TraceFinder database format to form a glucocorticoid mass spectrum database.

[0102] like Figure 6 As shown, the embodiment of the present invention discloses a quasi-targeted screening device for glucocorticoids in cosmetics, using the glucocorticoid mass spectrometry database described in the above embodiment. The quasi-targeted screening device includes a data acquisition unit 501, an extraction unit 502, a first matching unit 503, and a second matching unit 504, wherein:

[0103] The data acquisition unit 501 is used to acquire mass spectrum data of the sample to be tested;

[0104] An extraction unit 502 is used to perform chromatographic peak extraction on the mass spectrum data of the sample to be tested to obtain a primary mass spectrum peak and a secondary mass spectrum peak;

[0105] The first matching unit 503 is used to match the primary mass spectrum peak with the parent ion in the glucocorticoid mass spectrum database, and calculate the parent ion mass error and isotope distribution matching degree;

[0106] The second matching unit 504 is used to match the secondary mass spectrum peak with the fragment ions in the glucocorticoid mass spectrum database to obtain a matching result when the parent ion mass error is less than the specified error and the isotope distribution matching degree is greater than the specified matching degree.

[0107] like Figure 7 As shown, an embodiment of the present invention discloses a computer device, including a memory 601 storing executable program codes and a processor 602 coupled to the memory 601;

[0108] The processor 602 calls the executable program code stored in the memory 601 to execute the method for establishing the glucocorticoid mass spectrum database described in the above embodiments.

[0109] An embodiment of the present invention further discloses a computer-readable storage medium storing a computer program, wherein the computer program enables a computer to execute the establishment of a glucocorticoid mass spectrometry database or the quasi-targeted screening method for glucocorticoids in cosmetics described in the above embodiments.

[0110] The purpose of the above embodiments is to exemplarily reproduce and deduce the technical solution of the present invention, and to fully describe the technical solution, purpose and effect of the present invention. Its purpose is to make the public understand the disclosed content of the present invention more thoroughly and comprehensively, and it does not limit the scope of protection of the present invention.

[0111] The above embodiments are not exhaustive enumerations of the present invention, and there may be multiple other implementations not listed. Any replacement and improvement made without violating the concept of the present invention shall fall within the protection scope of the present invention.

Claims

1. A method for establishing a glucocorticoid mass spectrometry database, characterized in that: The method for establishing a mass spectrum database is executed by a computer device, the computer device is provided with an executable program code, and the computer device calls the executable program code to execute the method for establishing a mass spectrum database; the method for establishing a mass spectrum database includes: The computer device obtains simplified molecular linear input specification texts of several sample objects, wherein the sample objects are glucocorticoid compounds and / or derivatives of glucocorticoid compounds; The computer device converts the simplified molecular linear input specification text of each sample object into a molecular structure; The computer device adds hydrogen ions to the molecular structure to obtain positively charged molecular ions as parent ions, and calculates the mass-to-charge ratio of the parent ions; The computer device searches for the target specific group in the parent ion structure according to the specific sequence, simulates the breakage of the target specific group in sequence, and calculates the mass-to-charge ratio of the characteristic fragment ion obtained after each breakage; wherein the target specific group is part or all of the preset multiple specific breakage groups, and the multiple specific breakage groups include -F on the ring at the adjacent position of C=C, dihydrooxazolyl, -OH on the ring, -OH, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the non-ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring with a carbon number of <5, -F on the ring not at the adjacent position of C=C, alkanoyloxy on the non-ring with a carbon number of <6, phosphate, oxazolidinyl, -Cl on the ring, alkoxy on the ring, -Br on the ring, and carbonylmethyl carbon cation; The computer device summarizes the mass-to-charge ratio of the parent ion and the mass-to-charge ratio of each characteristic fragment ion to obtain a simulated mass spectrum of each sample object; The computer device organizes the simulated mass spectra of each sample object into a csv file according to the TraceFinder database format to form a glucocorticoid mass spectrum database; The plurality of preset specific cleavage groups are combined into a first cleavage sequence, a second cleavage sequence and a third cleavage sequence, wherein the first cleavage sequence is {dihydrooxazolyl, -OH on the ring, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring, -F on the ring that is not adjacent to C=C}, and the second cleavage sequence is {-F, dihydrooxazolyl, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring, -F on the ring that is not adjacent to C=C}. The third cleavage sequence is {ring-F, ring-OH}, the third cleavage sequence is {ring-alkanoyloxy, phosphate, oxazolidinyl, non-ring-alkanoyloxy, ring-Cl, ring-alkoxy, -OH, ring-Br, -OH, carbonylmethyl carbonium ion}; the specific sequence is a combination of the first cleavage sequence and the third cleavage sequence, or the specific sequence is a combination of the second cleavage sequence and the third cleavage sequence; the priority of the first cleavage sequence is higher than the priority of the third cleavage sequence, and the priority of the second cleavage sequence is higher than the priority of the third cleavage sequence; If the specific cleavage group -F does not appear on the ring adjacent to C=C of the parent ion structure, the specific sequence is {dihydrooxazolyl, -OH on the ring, alkanoyloxy on the ring with ≥5 carbon atoms, alkanoyloxy on a non-ring with ≥6 carbon atoms, acetal, alkanoyloxy on the ring, -F on the ring not adjacent to C=C, alkanoyloxy on the ring, phosphate, oxazolidinyl, alkanoyloxy on a non-ring, -Cl on the ring, alkoxy on the ring, -OH, -Br on the ring, -OH, carbonylmethyl carbonium ion}; If a specific cleavage group -F appears on the ring adjacent to the C=C position of the parent ion structure, the specific sequence is {-F on the ring adjacent to the C=C position, dihydrooxazolyl, alkanoyloxy on the ring with a carbon number ≥5, alkanoyloxy on a non-ring with a carbon number ≥6, acetal, alkanoyloxy on the ring, -F on the ring not adjacent to the C=C position, -OH on the ring, alkanoyloxy on the ring, phosphate, oxazolidinyl, alkanoyloxy on a non-ring, -Cl on the ring, alkoxy on the ring, -OH, -Br on the ring, -OH, carbonylmethyl carbonium ion}.

2. A quasi-targeted screening method for glucocorticoids in cosmetics, using the glucocorticoid mass spectrometry database of claim 1, characterized in that: The quasi-targeted screening method is performed by a computer device, the computer device is provided with a controller and a data storage device connected to a liquid chromatography high-resolution mass spectrometer, and the computer device is installed with TraceFinder software for performing the quasi-targeted screening method, and the quasi-targeted screening method includes: The computer device acquires mass spectrum data of the sample to be tested; The computer device performs chromatographic peak extraction on the mass spectrum data of the sample to be tested to obtain a primary mass spectrum peak and a secondary mass spectrum peak; The computer device matches the primary mass spectrum peak with the parent ion in the glucocorticoid mass spectrum database, and calculates the parent ion mass error and isotope distribution matching degree; If the parent ion mass error is less than the specified error and the isotope distribution matching degree is greater than the specified matching degree, the computer device matches the secondary mass spectrum peak with the fragment ions in the glucocorticoid mass spectrum database to obtain a matching result.

3. The quasi-targeted screening method for glucocorticoids in cosmetics according to claim 2, characterized in that: The specified error is 5 ppm and the specified matching degree is 90%.

4. A device for establishing a glucocorticoid mass spectrum database, characterized in that: include: A text acquisition unit, used to acquire simplified molecular linear input specification texts of several sample objects, wherein the sample objects are glucocorticoid compounds and / or derivatives of glucocorticoid compounds; A conversion unit, used for converting the simplified molecular linear input specification text of each sample object into a molecular structure; The simulated ionization unit is used to add hydrogen ions to the molecular structure to obtain positively charged molecular ions as parent ions and calculate the mass-to-charge ratio of the parent ions; The simulated fracture unit is used to search for the target specific group in the parent ion structure according to a specific sequence, simulate the fracture of the target specific group in sequence, and calculate the mass-to-charge ratio of the characteristic fragment ion obtained after each fracture; wherein the target specific group is part or all of the preset multiple specific fracture groups, and the multiple specific fracture groups include -F on the ring at the adjacent position of C=C, dihydrooxazolyl, -OH on the ring, -OH, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring with a carbon number of <5, -F on the ring not at the adjacent position of C=C, alkanoyloxy on the ring with a carbon number of <6, phosphate, oxazolidinyl, cyclopentane The present invention relates to a plurality of preset specific cleavage groups, wherein the first cleavage sequence is {dihydrooxazolyl, -OH on the ring, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring, -F on the ring that is not adjacent to C=C}, the second cleavage sequence is {-F, dihydrooxazolyl, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring, -F on the ring that is not adjacent to C=C, -OH on the ring}, and the third cleavage sequence is {alkanoyloxy on the ring, phosphate, oxazolyl The specific sequence is a combination of the first cleavage sequence and the third cleavage sequence, or the specific sequence is a combination of the second cleavage sequence and the third cleavage sequence; the priority of the first cleavage sequence is higher than the priority of the third cleavage sequence, and the priority of the second cleavage sequence is higher than the priority of the third cleavage sequence; if the specific cleavage group -F does not appear on the C=C adjacent ring of the parent ion structure, the specific sequence is {dihydrooxazolyl, -OH on the ring, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring, non-C=C adjacent =-F on the ring, alkanoyloxy on the ring, phosphate group, oxazolidinyl, alkanoyloxy on the non-ring, -Cl on the ring, alkoxy on the ring, -OH, -Br on the ring, -OH, carbonylmethyl carbocation}; if the specific cleavage group -F appears on the ring at the C=C adjacent position of the parent ion structure, the specific sequence is {-F on the ring at the C=C adjacent position, dihydrooxazolyl, alkanoyloxy on the ring with a carbon number of ≥5, alkanoyloxy on the non-ring with a carbon number of ≥6, acetal, alkanoyloxy on the ring, -F on the ring at a non-C=C adjacent position, -OH on the ring, alkanoyloxy on the ring, phosphate group, oxazolidinyl, alkanoyloxy on the non-ring, -Cl on the ring, alkoxy on the ring, -OH, -Br on the ring, -OH, carbonylmethyl carbocation}; A summary unit is used to summarize the mass-to-charge ratio of the parent ion and the mass-to-charge ratio of each characteristic fragment ion to obtain a simulated mass spectrum of each sample object; The sorting unit is used to sort the simulated mass spectrum of each sample object into a csv file according to the TraceFinder database format to form a glucocorticoid mass spectrum database.

5. A quasi-targeted screening device for glucocorticoids in cosmetics, using the glucocorticoid mass spectrometry database of claim 4, characterized in that: The quasi-targeted screening device comprises: A data acquisition unit, used to acquire mass spectrum data of the sample to be tested; An extraction unit is used to perform chromatographic peak extraction on the mass spectrum data of the sample to be tested to obtain a primary mass spectrum peak and a secondary mass spectrum peak; The first matching unit is used to match the primary mass spectrum peak with the parent ion in the glucocorticoid mass spectrum database, and calculate the parent ion mass error and isotope distribution matching degree; The second matching unit is used to match the secondary mass spectrum peak with the fragment ions in the glucocorticoid mass spectrum database to obtain a matching result when the mother ion mass error is less than the specified error and the isotope distribution matching degree is greater than the specified matching degree.

6. Computer equipment, characterized in that It comprises a memory storing executable program code and a processor coupled to the memory; the processor calls the executable program code stored in the memory to execute the method for establishing a glucocorticoid mass spectrometry database according to claim 1.

7. Computer device, characterized in that It comprises a controller and a data storage device connected to a liquid chromatography high-resolution mass spectrometer, wherein the data storage device is installed with TraceFinder software, and the controller calls the TraceFinder software to execute the quasi-targeted screening method for glucocorticoids in cosmetics according to claim 2 or 3.

8. A computer-readable storage medium, characterized in that The computer-readable storage medium stores a computer program, wherein the computer program enables a computer to execute the method for establishing a glucocorticoid mass spectrometry database according to claim 1.

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