Method and apparatus for establishing glucocorticoid mass spectrometry database, method and apparatus for applying glucocorticoid mass spectrometry database, and device

Abstract

Provided are a method and apparatus for automatically establishing a glucocorticoid mass spectrometry database, and a device. The method comprises: acquiring simplified molecular input line entry specification texts of several glucocorticoid compounds, converting same into molecular structures, and adding hydrogen ions, so as to obtain mass-to-charge ratios of parent ions; searching for target-specific groups according to a particular sequence, simulating the fragmentation thereof, and calculating mass-to-charge ratios of characteristic fragment ions, wherein the target-specific groups are some or all of a plurality of preset specific fragmentation groups; summarizing the mass-to-charge ratio of the parent ion and the mass-to-charge ratio of each characteristic fragment ion, so as to obtain a simulated mass spectrogram; and organizing the simulated mass spectrogram into a CSV file according to a TraceFinder database format, so as to form a glucocorticoid mass spectrometry database. The coverage range of a database can be expanded to 7,199 types; and a quasi-targeted screening method for glucocorticoids in cosmetics that is based on the database is provided, such that glucocorticoids are accurately screened from collected mass sample mass spectrometry data, thereby improving screening efficiency and accuracy.

Description

Establishment and application methods, devices, and equipment of glucocorticoid mass spectrometry database 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 issue of illegal additives in cosmetics has continued to attract the attention of consumers and market regulators. Glucocorticoids (GCs) are often illegally added to freckle-removing and whitening cosmetics and facial masks. While these cosmetics can quickly whiten and refine the skin when first used, long-term, continuous use can lead to local side effects such as vasodilation, hormone-dependent dermatitis, and irreversible skin atrophy. They can even cause serious systemic damage such as osteoporosis, hypertension, and diabetes. Therefore, relevant regulations explicitly prohibit the addition of glucocorticoids to 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 their spatial configuration, the number of glucocorticoid compounds can reach tens of thousands, posing significant challenges to detection technology and market regulation.

[0003] Currently, traditional detection methods for glucocorticoids include thin layer chromatography (TLC), gas chromatography-mass spectrometry, high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS / MS), and liquid chromatography-high-resolution mass spectrometry. Traditional detection methods typically use reference materials for the qualitative and quantitative analysis of known glucocorticoids, which have limited coverage and make it difficult to detect unknown glucocorticoid components.

[0004] Summary of the Invention

[0005] 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.

[0006] The first aspect of the present invention discloses a method for establishing a glucocorticoid mass spectrometry database, wherein the method for establishing a mass spectrometry 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 spectrometry database; the method for establishing a mass spectrometry database comprises:

[0007] 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;

[0008] The computer device converts the simplified molecular linear input specification text of each of the sample objects into a molecular structure;

[0009] 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;

[0010] The computer device searches for target specific groups in the parent ion structure according to a specific sequence, simulates and breaks the target specific groups in sequence, and calculates the mass-to-charge ratio of the characteristic fragment ions obtained after each break; wherein the target specific group is part or all of a plurality of preset specific break groups, and the plurality of specific break groups 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 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 C=C adjacent position, 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;

[0011] 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;

[0012] 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.

[0013] The second aspect of the present invention discloses a quasi-targeted screening method for glucocorticoids in cosmetics, which uses the glucocorticoid mass spectrometry database described in the first aspect. The quasi-targeted screening method is performed by a computer device, the computer device being provided with a controller and a data storage device connected to a liquid chromatography high-resolution mass spectrometer, and the computer device being installed with TraceFinder software for performing the quasi-targeted screening method. The quasi-targeted screening method comprises:

[0014] The computer device acquires mass spectrum data of the sample to be tested;

[0015] 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;

[0016] 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;

[0017] 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.

[0018] The third aspect of the present invention discloses a device for establishing a glucocorticoid mass spectrometry database, comprising:

[0019] a text acquisition unit, configured 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;

[0020] A conversion unit, configured to convert the simplified molecular linear input specification text of each sample object into a molecular structure;

[0021] 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;

[0022] A simulated fragmentation unit is used to search for target specific groups in the parent ion structure according to a specific sequence, simulate the fragmentation of the target specific groups in sequence, and calculate the mass-to-charge ratio of the characteristic fragment ions obtained after each fragmentation; wherein the target specific group is part or all of the preset multiple specific fragmentation groups, and the multiple specific fragmentation groups 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 ≥5, alkanoyloxy on the ring with a carbon number ≥6, acetal, alkanoyloxy on the ring with a carbon number <5, -F on the ring not at the C=C adjacent position, alkanoyloxy on the ring with a carbon number <6, phosphate, oxazolidinyl, -Cl on the ring, alkoxy on the ring, -Br on the ring, and carbonylmethyl carbon cation;

[0023] 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;

[0024] The collating unit is used to organize 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.

[0025] 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. The quasi-targeted screening device comprises:

[0026] A data acquisition unit, used to acquire mass spectrometry data of the sample to be tested;

[0027] The extraction unit is used to extract the chromatographic peaks of the mass spectrum data of the sample to be tested to obtain the primary mass spectrum peaks and the secondary mass spectrum peaks;

[0028] 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;

[0029] 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 mass error of the parent ion is less than the specified error and the isotope distribution matching degree is greater than the specified matching degree.

[0030] 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.

[0031] 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.

[0032] The beneficial effects of the present invention include:

[0033] (1) Glucocorticoids share the same cyclopentaphenanthrene nucleus structure, and their mass spectrometry fragmentation is highly specific. Based on the analysis of the secondary mass spectra of several glucocorticoids, the present invention summarizes the glucocorticoid-specific mass spectrometry fragmentation patterns and independently develops a glucocorticoid-specific mass spectrometry fragmentation algorithm using computer programming technology, thereby achieving the automated establishment of a glucocorticoid mass spectrometry database and the application of screening methods.

[0034] (2) The present invention can automatically simulate the mass spectrometry fragmentation process of glucocorticoids and generate characteristic glucocorticoid fragment ions in batches with one click. Furthermore, the present invention leverages the large-scale Internet chemical database to expand the number of glucocorticoid compounds to 7,199, whose structures represent almost all available glucocorticoids and their derivatives, thus increasing the screening coverage.

[0035] (3) The present invention utilizes a developed mass spectrometry fragmentation algorithm to simulate the fragmentation of glucocorticoid compounds, constructing a large-scale glucocorticoid mass spectrometry database. Ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry (UHPLC-Q-Orbitrap MS) is used to acquire data, and TraceFinder software is used for data processing to establish a quasi-targeted screening and analysis technology for glucocorticoids. This technology can accurately screen for glucocorticoids and their derivatives within massive amounts of high-resolution mass spectrometry data.

[0036] (4) Compared with 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 matching >90%, secondary fragment mass error <5ppm, and number of matches ≥2, achieving 7 identification points, which is far greater than the regulatory requirement of at least 4 identification points (IPs), greatly improving the identification accuracy. 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. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] The accompanying drawings herein illustrate 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.

[0038] 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.

[0039] FIG1 is a flow chart of a method for establishing a glucocorticoid mass spectrometry database disclosed in the present invention;

[0040] FIG2 is a schematic diagram of the chemical structure of the glucocorticoid disclosed in the present invention;

[0041] FIG3 is a detailed execution flow chart of step 140 in FIG1 disclosed in the present invention;

[0042] FIG4 is a flow chart of a quasi-targeted screening method for glucocorticoids in cosmetics disclosed in the present invention;

[0043] FIG5 is a schematic structural diagram of a device for establishing a glucocorticoid mass spectrometry database disclosed in the present invention;

[0044] FIG6 is a schematic structural diagram of a quasi-targeted screening device for glucocorticoids in cosmetics disclosed in the present invention;

[0045] FIG7 is a schematic structural diagram of a computer device disclosed in the present invention.

[0046] Explanation of the accompanying drawings: 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 commonly understood by those skilled in the art. In the context 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. "First, second..." used herein is merely used to distinguish 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 an element is considered to be "fixed to" another element, it can be directly fixed to the other element or there can be an intermediate element; when an element is considered to be "connected to" another element, it can be directly connected to the other element or there can be an intermediate element; when an element is considered to be "mounted on" another element, it can be directly mounted on the other element or there can be an intermediate element. When an element is considered to be "located on" another element, it can be directly located on the other element or there can be an intermediate element.

[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 that are 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. For ease of understanding the present invention, the following will be described in more detail with reference to the accompanying drawings of the specification sheets, taking the computer device as the execution subject. Wherein, the computer device is provided with an executable program code, and the computer device calls the executable program code for executing the method for establishing the mass spectrum database.

[0051] As shown in FIG1 , 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] The sample objects can be expanded to cover almost all available glucocorticoid compounds by using large-scale Internet chemical databases. For example, 100 glucocorticoid compounds are used as the 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, duplicates are removed, structures are confirmed, and enantiomers are merged. Finally, 7,199 glucocorticoids and their derivatives covering almost all available glucocorticoid compounds 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 using the Simplified Molecular Input Line Entry Specification (SMILES) text, and is converted into a computer-recognizable molecular structure mol by a computer device. The glucocorticoid structure is shown in Figure 2.

[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 fragmentation of the target specific groups in sequence, and calculates the mass-to-charge ratio of the characteristic fragment ions obtained after each fragmentation.

[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 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 C=C adjacent position, 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. Exemplary, it includes the 16 groups shown in Table 1 below:

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

[0061] Since glucocorticoid molecules are + After ionization in the ion source, positively charged quasi-molecular ions are formed. These quasi-molecular ions are then fragmented by collisions with energies of 10-30 NCE in the high-energy collision cell. Studies of this fragmentation process have revealed that glucocorticoid molecules fragment according to the fragmentation process listed in Table 1 if they contain any of the 16 groups listed. When two or more groups are present, the fragmentation of the different groups occurs in a specific order, which is related to the molecular structure.

[0062] 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 a first cleavage sequence A, a second cleavage sequence B, and a third cleavage sequence C. The first cleavage sequence A 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 that is not adjacent to C=C}; the second cleavage sequence B is {-F, 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 that is not adjacent to C=C, -OH on the ring}; and the third cleavage sequence C is {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 carbocation}.

[0063] Therefore, the specific sequence can be a combination of the first cleavage sequence and the third cleavage sequence, or the specific sequence can be a combination of the second cleavage sequence and the third cleavage sequence. In step 140, it can be determined whether the specific cleavage group -F is present on the ring adjacent to the C=C position of the parent ion structure. If the specific cleavage group -F is not present on the ring adjacent to the C=C position, 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 is present on the ring adjacent to the C=C position, the specific sequence of the combination of the second cleavage sequence B and the third cleavage sequence C is used.

[0064] 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, if the specific cleavage group -F does not appear on the ring adjacent to C=C, the specific sequence is {dihydrooxazolyl, -OH on the ring, alkanoyloxy on the ring with ≥5 carbon atoms, alkanoyloxy on the 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 the ring, -Cl on the ring, alkoxy on the ring, -OH, -Br on the ring, -OH, carbonylmethyl carbocation}; if C= If a specific cleavage group -F appears on the ring at the C-orbital position, the specific sequence is {-F on the ring at the C=C-orbital 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-orbital 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}.

[0065] When searching for a target specific group according to a 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 sequence. Whenever a target specific group is found in the molecular structure, a simulated cleavage is performed. This process is performed sequentially until all specific cleavage groups in the specific sequence are traversed. Specifically, the execution flow of step 140 can be shown in Figure 3. The groups in the molecular structure are searched in the order of Figure 3. If there are groups in Table 1, the cleavage is simulated according to the cleavage process, that is, the chemical bond is broken, the corresponding group is lost, and the fragment ion m / z after the cleavage is calculated. After the cleavage, the fragments continue to perform the group search->group cleavage->output fragment operation until all groups are found.

[0066] 150. 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.

[0067] 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.

[0068] The .csv file contains a table containing the ID of each sample object, simplified molecular linear input specification text, and the m / z values ​​of the parent ion and characteristic fragment ions. It should be noted that in subsequent data analysis methods, the glucocorticoid mass spectral database plays a decisive role in the matching results. The more glucocorticoid compounds included in the glucocorticoid mass spectral database, the wider the screening range, which can improve the accuracy of the screening results. To achieve automated glucocorticoid screening, the glucocorticoid mass spectral database was imported into TraceFinder 4.1 software in a specific format to achieve automated screening of actual sample data.

[0069] 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 patterns of glucocorticoid compounds, greatly improving the screening coverage of glucocorticoid compounds in cosmetics.

[0070] As shown in FIG4 , an embodiment of the present invention further discloses a quasi-targeted screening method for glucocorticoids in cosmetics. The glucocorticoid mass spectrometry database constructed in the above embodiment is applied. The quasi-targeted screening method for glucocorticoids in cosmetics is performed by a computer device, which is provided with a controller and a data storage device connected to a liquid chromatography high-resolution mass spectrometer. The computer device is installed with TraceFinder software for performing the quasi-targeted screening method. The quasi-targeted screening method includes the following steps 310 to 330:

[0071] 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.

[0072] Specifically, a Hypersil Gold C18 column (50 mm × 2.1 mm, 1.9 μm) was selected as the ultra-high performance liquid chromatography column. A gradient elution procedure was adjusted based on column adaptation. Under these chromatographic conditions, 100 glucocorticoid compounds were effectively separated, with symmetrical peak shapes. This method, which addresses the potential for large logP values ​​of unknown glucocorticoid compounds, uses a 2-minute 100% acetonitrile elution, effectively eluting the vast majority of glucocorticoid compounds.

[0073] Using ESI + The HPLC-MS / MS mode was used, with the primary and secondary resolutions set to 70,000 and 17,500, respectively. The mass scan range was m / z 200-1500, and post-collision superposition was performed at three different normalized collision energies (NCEs): 10, 20, and 35. Under these mass spectrometric conditions, most glucocorticoid compounds showed a certain response, and both primary and secondary mass spectrometric peaks were normally collected.

[0074] 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.

[0075] Specifically, the computer device in step 320 may calculate the parent ion mass error in the following manner:

[0076] 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 using the following formula (1):

[0077] 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.

[0078] In step 320, the computer device may calculate the isotope distribution matching degree in the following manner:

[0079] The computer device matches the primary mass spectral peaks with the parent ions in the glucocorticoid mass spectral database, calculates the similarity between the measured intensities of multiple isotope mass spectral peaks and the theoretical intensities of the corresponding isotope mass spectral peaks, and determines the similarity as the isotope distribution matching degree. Preferably, multiple isotope mass spectral peaks with measured intensities greater than 2% can be selected for calculation.

[0080] For example, it can be calculated by the following formula (2):

[0081] Where MA represents the isotope distribution matching degree, Mi represents the measured intensity of the i-th isotope mass spectrum peak, Ti represents the theoretical intensity of the i-th isotope mass spectrum peak, and n represents the total number of isotope mass spectrum peaks.

[0082] 330. 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.

[0083] 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 matching is automatically performed according to the set parameters (secondary fragment mass error <5ppm, number of matches ≥2). If the secondary fragment mass error is <5ppm, the fragment match is successful. If the number of matches is ≥2, it means that the secondary mass spectrum peak successfully matches the compound in the database. The more successful secondary fragment matches, the higher the accuracy. Finally, the matching compound in the database is output as the matching result.

[0084] In summary, this method, using TraceFinder 4.1 software and setting parameters of precursor ion mass error <5 ppm, isotope pattern matching >90%, secondary fragment mass error <5 ppm, and number of matches ≥2, achieved seven identification points (IPs), far exceeding the regulatory requirement of at least four identification points (IPs), significantly improving identification accuracy. This method directly outputs screening results, significantly reducing manual intervention, ease of analysis difficulty and time investment, and significantly improving screening efficiency and accuracy.

[0085] The quasi-targeted screening method established by the present invention was used to screen 955 batches of glucocorticoids in 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 bold types are new glucocorticoids that were screened out for the first time from actual samples on the market, with a content of 5.4mg / kg to 28.6mg / kg. The relevant departments should strengthen supervision on the illegal addition of these new glucocorticoids. The results show that this method has great technical advantages in screening coverage, accuracy and automation when applied to large-scale rapid screening of glucocorticoids in cosmetics, and has broad application prospects.

[0086] Table 2 Actual sample screening positive results

[0087] The quasi-targeted screening method established by the present invention was used to screen and analyze 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), parent ion isotope matching score 100%, parent ion isotope distribution mass spectrum peak matching all 5, secondary mass spectrum peak matching number 5, showing that all results match. Combined with its fragmentation pattern, the fragment m / z 393.1708, error-3.86ppm is [M+H] + [M+H-HF] obtained by neutral loss of HF from the parent ion + 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 continued to be lost: 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). The results matched one parent ion and five secondary fragments, resulting in 2 + 2.5 * 5 = 14.5 identification points, a total of 14.5 identification points, far exceeding the regulatory requirement of 4. The screening results were consistent with those of the reference substance, demonstrating the high accuracy and automation of this method, enabling automatic matching to yield correct results and covering a wide range of compounds.

[0088] As shown in FIG5 , an embodiment of the present invention discloses a device for establishing a glucocorticoid mass spectrometry database, comprising a text acquisition unit 401 , a conversion unit 402 , a simulated ionization unit 403 , a simulated fragmentation unit 404 , a summary unit 405 , and an arrangement unit 406 , wherein:

[0089] A text acquisition unit 401 is configured 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;

[0090] A conversion unit 402 is used to convert the simplified molecular linear input specification text of each sample object into a molecular structure;

[0091] 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;

[0092] The simulated fragmentation unit 404 is used to search for target specific groups in the parent ion structure according to a specific sequence, simulate the fragmentation of the target specific groups in sequence, and calculate the mass-to-charge ratio of the characteristic fragment ions obtained after each fragmentation; wherein the target specific groups are part or all of the preset multiple specific fragmentation groups, and the multiple specific fragmentation groups 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 ≥5, alkanoyloxy on the ring with a carbon number ≥6, acetal, alkanoyloxy on the ring with a carbon number <5, -F on the ring not at the C=C adjacent position, alkanoyloxy on the ring with a carbon number <6, phosphate, oxazolidinyl, -Cl on the ring, alkoxy on the ring, -Br on the ring, and carbonylmethyl carbon cation.

[0093] 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;

[0094] The arranging unit 406 is used to arrange 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.

[0095] As shown in FIG6 , an embodiment of the present invention discloses a quasi-targeted screening device for glucocorticoids in cosmetics. The glucocorticoid mass spectrometry database described in the above embodiment is applied. 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:

[0096] The data acquisition unit 501 is used to acquire mass spectrometry data of the sample to be tested;

[0097] Extraction unit 502, used to perform chromatographic peak extraction on the mass spectrum data of the sample to be tested to obtain primary mass spectrum peaks and secondary mass spectrum peaks;

[0098] 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;

[0099] 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.

[0100] As shown in FIG7 , an embodiment of the present invention discloses a computer device, including a memory 601 storing executable program code and a processor 602 coupled to the memory 601 ;

[0101] 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.

[0102] 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.

[0103] The purpose of the above embodiments is to exemplify 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 enable the public to have a more thorough and comprehensive understanding of the disclosed content of the present invention, and it does not limit the scope of protection of the present invention.

[0104] The above embodiments are not exhaustive and may include many other embodiments not listed above. Any replacements and improvements made without violating the concept of the present invention are within the scope of protection 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, which is provided with an executable program code. 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 of the sample objects 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 target specific groups in the parent ion structure according to a specific sequence, simulates and breaks the target specific groups in sequence, and calculates the mass-to-charge ratio of the characteristic fragment ions obtained after each break; wherein the target specific group is part or all of a plurality of preset specific break groups, and the plurality of specific break groups 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 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 C=C adjacent position, 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; 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.

2. The method for establishing a glucocorticoid mass spectrometry database according to claim 1, wherein: If the specific cleavage group -F does not appear on the ring adjacent to the C=C position 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 the C=C position, 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 carbenium ion}.

3. The method for establishing a glucocorticoid mass spectrum database according to claim 1, wherein: If a 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 ≥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 carbocation}.

4. A quasi-targeted screening method for glucocorticoids in cosmetics, using the glucocorticoid mass spectrometry database according to any one of claims 1 to 3, characterized in that: The quasi-targeted screening method is performed by a computer device, which 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.

5. The quasi-targeted screening method for glucocorticoids in cosmetics according to claim 4, characterized in that: The specified error is 5 ppm, and the specified matching degree is 90%.

6. A device for establishing a glucocorticoid mass spectrum database, characterized in that: include: a text acquisition unit, configured 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, configured to convert 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; A simulated fragmentation unit is used to search for target specific groups in the parent ion structure according to a specific sequence, simulate the fragmentation of the target specific groups in sequence, and calculate the mass-to-charge ratio of the characteristic fragment ions obtained after each fragmentation; wherein the target specific group is part or all of the preset multiple specific fragmentation groups, and the multiple specific fragmentation groups 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 ≥5, alkanoyloxy on the ring with a carbon number ≥6, acetal, alkanoyloxy on the ring with a carbon number <5, -F on the ring not at the C=C adjacent position, alkanoyloxy on the ring with a carbon number <6, phosphate, oxazolidinyl, -Cl on the ring, alkoxy on the ring, -Br on the ring, and carbonylmethyl carbon cation; 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 collating unit is used to organize 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.

7. A quasi-targeted screening device for glucocorticoids in cosmetics, using the glucocorticoid mass spectrometry database according to claim 6, characterized in that: The quasi-targeted screening device comprises: A data acquisition unit, used to acquire mass spectrometry data of the sample to be tested; The extraction unit is used to extract the chromatographic peaks of the mass spectrum data of the sample to be tested to obtain the primary mass spectrum peaks and the secondary mass spectrum peaks; 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 mass error of the parent ion is less than the specified error and the isotope distribution matching degree is greater than the specified matching degree.

8. Computer equipment, characterized in that It comprises a memory storing an 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 any one of claims 1 to 3.

9. 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 4 or 5.

10. 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 any one of claims 1 to 3.

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