Method for rapidly screening and confirming 120 anti-infection drugs in cosmetics

Abstract

The invention provides a method for rapidly screening and confirming 120 anti-infective drugs in cosmetics, which comprises the following steps: preparing a mixed solution of standard substances of 120 anti-infective drugs and a to-be-detected sample solution, adopting a real-time direct analysis ion source to complete the ionization process of a target compound, and adopting a high-resolution mass spectrum to determine the content of 120 anti-infective drugs. And based on a positive ion and negative ion first-level full scanning-data dependence second-level scanning mode, collecting data and processing the data. The invention provides a detection method for rapidly screening 120 anti-infective drugs in cosmetics by real-time direct analysis ion source-high resolution mass spectrometry, the real-time direct analysis ion source-high resolution mass spectrometry is adopted, and compared with a traditional chromatographic separation technology, complex sample pretreatment and time-consuming chromatographic analysis are not needed, and the detection method has the advantages that the detection method is simple and convenient, and the detection cost is low. The method reduces the usage amount of chemical reagents, shortens the test period, avoids the interference of sample matrixes, and can be used for rapid screening of various cosmetic matrixes.

Description

Technical Field

[0001] The present invention belongs to the technical field of cosmetics detection methods, and relates to a method for rapidly screening 120 anti-infective drugs in cosmetics, and specifically to a method for rapidly screening 120 anti-infective drugs in cosmetics using a real-time direct analysis ion source-high-resolution mass spectrometer. Background Art

[0002] Anti-infective drugs include sulfonamides, quinolones, macrolides, tetracyclines, etc., which have good bactericidal and antibacterial effects. However, some unscrupulous merchants often illegally add anti-infective drugs to cosmetics in order to achieve antibacterial and anti-inflammatory purposes. If consumers use cosmetics that have been illegally added with anti-infective drugs for a long time, it will destroy the normal flora on the skin surface, causing adverse reactions such as rashes and allergies, and will also lead to drug resistance, increasing the difficulty of subsequent treatment. According to my country's "Technical Specifications for Cosmetic Safety (2015 Edition)" (hereinafter referred to as the "Technical Specifications"), the use of anti-infective drugs in cosmetics is prohibited.

[0003] Currently, the screening methods for anti-infective substances in cosmetics mostly use liquid chromatography tandem mass spectrometry, high-performance liquid chromatography-electrostatic field orbital trap high-resolution mass spectrometry, and high-performance liquid chromatography-time-of-flight high-resolution mass spectrometry. The above methods take a long time to detect large quantities of samples. Therefore, establishing a fast and accurate screening method will help improve the efficiency of supervision and the intensity of crackdown on the illegal addition of anti-infective drugs in cosmetics.

[0004] Direct analysis in real time (DART) is a novel open, atmospheric-pressure in-situ ionization technology that does not require complex sample pretreatment and time-consuming chromatographic analysis. It has the advantages of significantly reducing organic solvent consumption, shortening sample analysis time, and being environmentally friendly. It has broad application prospects in the field of rapid screening of cosmetics.

[0005] However, in the case of multi-substance detection, how to take into account the detection conditions of each test substance and avoid mutual interference between the substances to achieve rapid and accurate detection of each test object at the same time is still an issue that needs to be explored urgently. Summary of the Invention

[0006] In response to the above technical problems, the purpose of the present invention is to establish a rapid screening method for 120 anti-infective drugs in cosmetics, which is conducive to improving the daily analysis throughput of cosmetics, enhancing the efficiency of risk monitoring, and improving the technical support system for cosmetics safety control. The present invention provides a method for rapid screening of 120 anti-infective drugs in cosmetics using real-time DART-high resolution mass spectrometry (HRMS). By utilizing the resolution of the Q-Orbitrap mass spectrometer and the data acquisition mode of the first full scan-data-dependent second scan mode, the accurate mass number of the primary parent ion and secondary fragment ion of the target compound is obtained, thereby achieving accurate, rapid and effective screening of 120 anti-infective drugs in cosmetics.

[0007] The technical solutions of the present invention are as follows:

[0008] A method for rapid screening of 120 anti-infective drugs in cosmetics using direct analysis in real time-high resolution mass spectrometry (DART-HRMS). The 120 anti-infective drugs are:

[0009]

[0010] The method comprises the following steps:

[0011] (1) Preparation of a mixed series of standard working solutions of 120 anti-infective drugs:

[0012] The 120 anti-infective drug standard substances are mixed, diluted with methanol, and a mixed solution of 120 anti-infective drug standard substances is prepared; the mixed solution of 120 anti-infective drug standard substances is diluted with 80% methanol to prepare a mixed series standard working solution of 120 anti-infective drugs;

[0013] (2) Prepare the sample solution to be tested:

[0014] The cosmetics to be tested are diluted with acetonitrile, ultrasonicated, shaken, and the supernatant is separated as the sample solution to be tested;

[0015] If the extracted ion current (EIC) response is found to be more than 5×10 9 , then dilute moderately with 80% methanol.

[0016] (3) Using a real-time direct analysis ion source on the mixed solution of the standard substance prepared in steps (1) and (2) and the sample solution to be tested, the ionization process of the target compound is completed:

[0017] Real-time direct analysis ion source conditions:

[0018] The positive ion voltage is 300~400V, and the negative ion voltage is -300~-400V;

[0019] Gas temperature is 350-450℃;

[0020] The ionized gas is helium, and the pressure is 0.50 MPa;

[0021] The standby gas is nitrogen with a pressure of 0.50 MPa;

[0022] Injection parameters:

[0023] The injection mode is 12-Dip-It Samplers mode;

[0024] Sampling was performed by spot sampling with a sample volume of 3 to 5 μL;

[0025] In a particular embodiment, the sample spotting method is to use a glass rod provided with the DART, place it on a provided sample injector, and use a pipette to draw 3 to 5 μL of the test solution onto the tip of the glass rod. The sample spotting volume is 3 to 5 μL.

[0026] The injection speed is 0.6 mm / s;

[0027] (4) Using high-resolution mass spectrometry, based on positive and negative ion modes, data-dependent secondary ion full scan (FullMS, Intensity, Dynamic Exclusion, Targeted Mass, ddMS2) scanning mode;

[0028] Full MS parameters: scan range 100-1000, resolution 70000;

[0029] dd-MS 2 Parameters: resolution 17500, normalized collision energy (NCE) 20, 40, 60, 80 eV, where the NCE of ciclopirox is 80 eV;

[0030] (5) Data processing:

[0031] Extract the primary mass spectra and secondary mass spectra of 120 anti-infective drugs from the standard substance collection data, and determine the accurate mass of the parent ion and secondary mass spectrum fragment ion of each substance of the 120 anti-infective drugs;

[0032] Extract sample collection data, extract primary mass spectra, and preliminarily and quickly screen out anti-infective drugs in cosmetics. At the same time, extract secondary mass spectra for the screened anti-infective drugs, and combine them with secondary characteristic ions for further confirmation to achieve accurate characterization.

[0033] Furthermore, in the mixed series of standard working solutions of 120 anti-infective drugs in step (1), the concentration of each standard substance is one or more concentrations between 10 and 5000 ng / mL.

[0034] Furthermore, the acetonitrile dilution ratio of the cosmetic to be tested in step (2) is 2 to 200 mg / mL. Preferably, the acetonitrile dilution ratio of the cosmetic to be tested in step (2) is 20 mg / mL.

[0035] Furthermore, the ultrasonication time in step (2) is 15 minutes.

[0036] Furthermore, the separation in step (2) is centrifugal separation or filtration separation.

[0037] Furthermore, the centrifugation condition is 5000 rpm for 5 min, and the filtration is microporous membrane filtration.

[0038] Furthermore, when the content of the substance to be tested is high (for example, the extracted ion chromatogram (EIC) response exceeds 5×10 9 When the supernatant is diluted with 80% methanol, the step (2) further comprises diluting the supernatant.

[0039] Furthermore, the injection speed in step (3) is 0.6 mm / s.

[0040] Furthermore, the secondary parent ion in the Targeted Mass in step (4) is set as:

[0041]

[0042]

[0043]

[0044]

[0045] The method of the present invention needs to be set according to the above-mentioned positive and negative ion modes and the selection of parent ions, otherwise secondary missed detection (lack of secondary mass spectrum information) is likely to occur.

[0046] In one embodiment, the measured secondary mass spectrometry fragment ions are as follows. If the detection conditions of the present invention are exactly the same, no standard is required and the secondary data here can be directly referenced, with an error range of 10 ppm allowed:

[0047]

[0048]

[0049]

[0050]

[0051] In one embodiment, the cosmetic is a cream, lotion, lotion, or the like.

[0052] The beneficial effects of the present invention are:

[0053] 1. This invention proposes a method for rapid screening of 120 anti-infective drugs in cosmetics using real-time direct analysis ion source-high-resolution mass spectrometry. This method uses real-time DART-HRMS. Compared to traditional chromatographic separation techniques, it eliminates the need for complex sample pretreatment and time-consuming chromatographic analysis, reduces the use of chemical reagents, shortens the testing cycle, and avoids interference from the sample matrix. It can be used for rapid screening of various cosmetic matrices.

[0054] 2. The present invention can directly determine ciclopirox olamine without first subjecting the standard solution / sample solution to methyl esterification and derivatization with dimethyl sulfate before determination, thus simplifying the pretreatment process and avoiding the use of the toxic reagent dimethyl sulfate;

[0055] 3. This invention can rapidly screen 120 anti-infective drugs in cosmetics, complete data analysis and collection in a relatively short period of time, and provide technical support for product quality control in the cosmetics industry.

[0056] 4. The present invention is simple, fast and efficient. When testing the same batch of samples, only one sample preparation is required to screen 120 anti-infective drugs. There is no need for multiple preparations and subsequent screening, which greatly improves the efficiency of supervision work. BRIEF DESCRIPTION OF THE DRAWINGS

[0057] Figure 1 The extracted ion chromatograms of 120 mixed standard solutions are shown in Figure 1. The left, middle, and right columns are numbered 1-8, 9-16, and 17-24 from top to bottom, respectively.

[0058] Figure 2 The extracted ion chromatograms of 120 mixed standard solutions are shown in Figure 1. The left, middle, and right columns are numbered 24-32, 33-40, 41-45, and 47-49 from top to bottom, respectively.

[0059] Figure 3 The extracted ion chromatograms of 120 mixed standard solutions are shown in Figure 1. The left, middle, and right columns are numbered 50-57, 58-65, and 66-73 from top to bottom, respectively.

[0060] Figure 4 The extracted ion chromatograms of 120 mixed standard solutions are shown in Figure 1. The left, middle, and right columns are numbered 74-80, 82, 83-90, and 91-98 from top to bottom, respectively.

[0061] Figure 5The extracted ion chromatograms of 120 mixed standard solutions are shown in Figure 1. The left, middle, and right columns are numbered 99-106, 107-115, 46, 81, and 116-120 from top to bottom, respectively.

[0062] Figure 6 is the DART-HRMS primary mass spectrum and secondary mass spectrum of ciclopirox olamine; wherein, Figure 6 A is the DART-HRMS primary mass spectrum of ciclopirox olamine, Figure 6 B is the DART-HRMS secondary mass spectrum of ciclopirox olamine;

[0063] Figure 7 This is the extracted ion chromatogram of the positive sample solution, where the left, middle, and right columns are numbered 1-8, 9-16, and 17-24 from top to bottom respectively;

[0064] Figure 8 This is the extracted ion chromatogram of the positive sample solution, where the left, middle, and right columns are numbered 24-32, 33-40, 41-45, and 47-49 from top to bottom respectively;

[0065] Figure 9 This is the extracted ion chromatogram of the positive sample solution, where the left, middle, and right columns are numbered 50-57, 58-65, and 66-73 from top to bottom respectively;

[0066] Figure 10 This is the extracted ion chromatogram of the positive sample solution, where the left, middle, and right columns are numbered 74-80, 82, 83-90, and 91-98 from top to bottom respectively;

[0067] Figure 11 This is the extracted ion chromatogram of the positive sample solution, where the left, middle and right columns are substances numbered 99-106, 107-115, 46, 81, and 116-120 from top to bottom respectively. DETAILED DESCRIPTION

[0068] The present invention is further explained below with reference to the following examples, but the examples do not limit the present invention in any form.

[0069] Example 1

[0070] 1. Reagents and instruments

[0071] 1.1 Standard substances and reagents

[0072] Standard substances: Single standards of 120 anti-infective drug standards including dimetridazole (Shanghai Anpu Cuishi Standard Technology Service Co., Ltd.).

[0073] Methanol (chromatographic grade, Merck, Germany), acetonitrile (chromatographic grade, Merck, Germany).

[0074] High-purity N2 gas, He gas (purity 99.999%).

[0075] 1.2 Instruments

[0076] Q-Exactive mass spectrometer (Thermo Fisher Scientific, USA); DART real-time direct analysis source (Hydroxytech Corporation); MSE224S-CE electronic balance (Sartorius, Germany); UA22MFD ultrasonic cleaner (Wiggens, Germany); ultrapure water system (Millipore, USA).

[0077] 2 Experimental methods

[0078] 2.1 Preparation of standard solution

[0079] (1) Preparation of standard solution:

[0080] (1-1) Standard stock solution (2 mg / mL): Accurately weigh 20 mg of each standard substance, dissolve it in methanol, and dilute to 10 mL to prepare a standard stock solution (2 mg / mL) of each component. Store frozen at -18°C.

[0081] (1-2) Mixed solution of 120 anti-infective drug standard substances (10 μg / mL): Pipette 0.05 mL of the standard stock solution of each component prepared in (1-1) into a 10 mL volumetric flask, dilute with methanol and make up to the mark, mix well, and prepare a mixed solution of 120 anti-infective drug standard substances (10 μg / mL).

[0082] (1-3) Mixed series of standard working solutions of 120 anti-infective drugs: Accurately pipette an appropriate amount of a mixed solution (10 μg / mL) of 120 anti-infective drug standard substances, dilute with 80% methanol, and prepare a series of standard working solutions with concentrations of 10, 20, 50, 100, 200, 500, 1000, and 5000 ng / mL.

[0083] (2) Preparation of isomer standard solution:

[0084] (2-1) Isomeric standard stock solution (2 mg / mL): Accurately weigh 20 mg of each isomeric standard substance, dissolve them in methanol, and dilute to 10 mL. Store frozen at -18°C.

[0085] (2-2) Isomers Single Standard Working Solution (2 μg / mL): Pipette 0.01 mL of each isomeric component standard stock solution prepared in (2-1) into a 10 mL volumetric flask. Dilute the single standard stock solution to the mark with 80% methanol and mix thoroughly to prepare a 2 μg / mL single standard working solution. This isomers single standard working solution is used for method development.

[0086] The isomers or similar isomers are:

[0087]

[0088] * Groups 2 and 10 are not isomers, but because succinylsulfathiazole and clindamycin phosphate are cleaved into sulfathiazole and clindamycin, respectively, in DART, the monitored ions are the same, similar to "isomers".

[0089] (3) Preparation of single-standard working solution:

[0090] In order to determine whether the isomeric fragments are identical to the fragments of the standard structure, a single-standard working solution was prepared in this experiment:

[0091] Single standard stock solution (2 mg / mL): Accurately weigh 10 mg of each standard substance, dissolve it in methanol and make up to 5 mL, then freeze and store at -18°C.

[0092] Single-label working solution (2 μg / mL): Measure 10 μL of the single-label stock solution, dilute to 10 mL with 80% methanol, and mix thoroughly.

[0093] 2.2 Sample pretreatment

[0094] Weigh 0.2 g of cosmetics into a 10 mL centrifuge tube, add 2 mL of acetonitrile and vortex to disperse, then dilute to 10 mL, sonicate for 15 min, shake well, centrifuge at 5000 rpm for 5 min, and collect the supernatant to obtain the sample solution (20 mg / mL).

[0095] 2.3 Instrument parameters

[0096] 2.3.1Q-Exactive mass spectrometry parameters:

[0097] Positive and negative ion modes, data-dependent secondary ion full scan (Full MS / Intensity / Dynamic Exclusion / Targeted Mass / ddMS2) scanning mode. Full MS parameters: scan range 100-1000, resolution 70000; dd-MS 2 Parameters: resolution 17500; normalized collision energy (NCE) 20, 40, and 60 eV (NCE of ciclopirox olamine is 80 eV); "Targeted Mass list" is shown in Table 1, and isomers are shown in Table 2.

[0098] Table 1 Settings for secondary precursor ions in the Targeted Mass list

[0099]

[0100]

[0101]

[0102]

[0103] Table 2

[0104] serial number Serial number Chinese name Precursor ion m / z serial number Serial number Chinese name Precursor ion m / z 1 6 Ternidazole 186.08732 13 39 Sulfadiazine 285.02075 2 7 secnidazole 186.08732 14 48 Sulfadoxine 311.08085 3 18 Sulfathiazole 256.02089 15 49 Sulfadiazolidine 311.08085 4 25 Sulfatrol 268.07504 16 63 Succinylsulfathiazole 256.02089 5 26 Sulfisoxazole 268.07504 17 84 Miconazole 414.99330 6 27 Sulfamethoxazole 268.07504 18 85 Isoconazole 414.99330 7 33 Sulfadiazine 279.09102 19 86 Clindamycin 425.18715 8 34 Sulfadiazine 279.09102 20 87 Epianhydrotetracycline hydrochloride 427.14998 9 35 Sulfadiazine 281.07029 21 88 Anhydrotetracycline 427.14998 10 36 Sulfadiazine 281.07029 22 100 Clindamycin phosphate 425.18715 11 37 Sulfadiazine 281.07029 23 91 tetracycline 445.16054 12 38 Sulfadiazine 285.02075 24 92 doxycycline 445.16054

[0105] 2.3.2 Real-time direct analysis ion source conditions and injection acquisition parameters:

[0106] The positive ion voltage was 300 V, the negative ion voltage was -300 V, the temperature was 350°C, the ionization gas was helium, and the pressure was 0.50 MPa; the standby gas was nitrogen, and the injection speed was 0.6 mm / s.

[0107] 2.3.3 Injection method:

[0108] The injection mode is the 12-Dip-It Samplers mode; sampling is performed by spot sampling: the glass rod provided with the DART is placed on the provided injector, and 5 μL of a series of standard working solutions, isomer working solutions, single-label working solutions, and test solutions are pipetted onto the bottom of the glass rod for testing.

[0109] The glass rod device was placed between the DART-MS ion source gas flow outlet and the mass spectrometer inlet.

[0110] 2.3.4 Result determination method:

[0111] Secondary mass spectra of standard substance solutions were collected for library construction, and two characteristic fragments were selected (as shown in Table 3). Sample data was collected, primary mass spectra were extracted, and preliminary and rapid screening of anti-infective drugs in cosmetics was performed. Secondary mass spectra were also extracted for these screened anti-infective drugs, and further confirmation was performed using secondary characteristic ions to achieve accurate identification.

[0112] 2.4 Results 2.4.1 Determination of standard solution

[0113] In positive and negative ion Full MS / Intensity / Dynamic Exclusion / Targeted Mass / ddMS 2In scanning mode, 5 μL of a mixed series of standard working solutions of 120 anti-infective drugs at concentrations of 10, 20, 50, 100, 200, 500, 1000, and 5000 ng / mL was pipetted and spotted on the bottom of a glass rod. Automatic injection was performed to collect mass spectra of each substance of the 120 anti-infective drugs. The accurate mass of the parent ion of the substance was determined by a primary full scan. When the parent ion of the target compound was detected to reach the set threshold, the mass spectrometer automatically triggered a secondary scan to obtain the accurate mass of the secondary fragment ion. The accurate mass of the parent ion of each substance and the accurate mass of the secondary mass spectrum fragment ion were extracted and determined using the instrument software. Specific information is shown in Table 3.

[0114] Furthermore, injection results of the single-label working solution and the isomeric working solution showed that the isomeric product ions were identical to those of the corresponding standard structures, thus eliminating the need for isomeric injection during actual testing. Because the single-label working solution is used to identify isomeric fragments, the method of the present invention allows for the preparation of mixed standards, eliminating the need for separate preparations of the single-label working solution.

[0115] The extracted ion diagram of 5μg / mL mixed standard working solution is as follows Figures 1 to 5 As shown, the results show that the characteristic ion extraction peaks of 120 anti-infective drugs are clearly identifiable and have good reproducibility; 120 substances can be screened in high throughput within 1 minute with high screening efficiency.

[0116] Ciclopirox olamine can be used to determine [M+H]+ without derivatization. The primary and secondary mass spectra are shown in Figure 2. Figure 6 shown.

[0117] Table 3 Mass spectrometry results and detection limits of 120 anti-infective drugs

[0118]

[0119]

[0120]

[0121]

[0122] 2.4.2 Determination of detection limit

[0123] The detection limits of various substances were determined by adding 120 anti-infective drugs at different concentrations to blank cosmetic extracts. As shown in Table 2, the detection limits of the 120 anti-infective drugs were between 10 ng / mL and 1 μg / mL.

[0124] 2.4.3 Actual sample measurement results

[0125] The method established in this study was used to test commercially available cosmetic samples. Two glass rods were used to inject each sample. Extracted ion maps and primary precise mass numbers were used to conduct preliminary qualitative screening of 120 possible anti-infective drugs, and secondary characteristic ions were used for further confirmation.

[0126] The screening results showed that anti-infective drugs miconazole / isoconazole were detected in 1 batch of samples. Figures 7 to 11 , specifically, Figure 10 Obvious extracted ion current peaks appeared in channels 84 and 85 (the extracted ion was m / z 414.99274), so it can be determined that the anti-infective drugs miconazole / isoconazole were detected in the sample to be tested.

[0127] Comparative experiment

[0128] Comparative Example 1

[0129] This experiment investigated the effects of 200°C, 250°C, 300°C, 350°C, 400°C, 450°C, and 500°C on ionization efficiency. When the temperature is too low, metastable plasma formation becomes difficult, resulting in a very weak signal. When the temperature is too high, thermal decomposition of the analyte may occur, hindering detection. The results show that the analyte signal response is higher at 350-450°C. Therefore, the ionization gas temperature of 350-450°C was ultimately selected.

[0130] Comparative Example 2

[0131] This experiment examined the effects of different gate voltages: 200V, 250V, 300V, 350V, 400V, 450V, and 500V. The ion response intensity increased with increasing gate voltage, reaching a maximum value before weakening. The response was best at 300V to 400V, so this range was chosen for this experiment.

[0132] Comparative Example 3

[0133] This experiment examined the ionization effects of injection speeds of 0.4, 0.6, and 0.8 mm / s. When the injection speed is too fast, the number of ions entering the mass spectrometer decreases, resulting in a lower response. However, when the injection speed is too slow, the sample surface is more fully exposed to the decomposition gas and the mass spectrometer, increasing the amount entering the mass spectrometer and thus enhancing the signal. However, this can also lead to tailing of the mass spectrum peaks and even double or triple peaks. For these considerations, an injection speed of 0.6 mm / s was selected for this experiment.

[0134] Using optimized injection temperature, voltage, and carrier gas temperature, and carefully controlling the spotting location and droplet size when spotting can effectively avoid double peaks, tailing, and affecting the response of target analytes.

[0135] Comparative Example 4

[0136] This experiment examined the response when using acetonitrile, acetonitrile + saturated sodium chloride (80:20, v / v), 20% methanol, and 80% methanol as the extraction solvent. Acetonitrile produced the best peak elution of the target compound, with the highest amount, higher response, and better peak shape, so acetonitrile was selected as the extraction solvent for this experiment.

[0137] The embodiments provided above are not intended to limit the scope of the present invention, nor are the steps described to limit their execution order. Any obvious improvements to the present invention made by those skilled in the art in combination with existing common knowledge are also within the scope of protection defined by the claims of the present invention.

Claims

1. A method for rapid screening of 120 anti-infective drugs in cosmetics using real-time direct analysis and high-resolution mass spectrometry. The 120 anti-infective drugs are: It is characterized by: The method comprises the following steps: (1) Preparation of a mixed series of standard working solutions of 120 anti-infective drugs: The 120 anti-infective drug standard substances are mixed, diluted with methanol, and a mixed solution of 120 anti-infective drug standard substances is prepared; the mixed solution of 120 anti-infective drug standard substances is diluted with 80% methanol to prepare a mixed series standard working solution of 120 anti-infective drugs; (2) Prepare the sample solution to be tested: The cosmetics to be tested are diluted with acetonitrile, ultrasonicated, shaken, and the supernatant is separated as the sample solution to be tested; (3) Using a real-time direct analysis ion source on the mixed solution of the standard substance prepared in steps (1) and (2) and the sample solution to be tested, the ionization process of the target compound is completed: Real-time direct analysis ion source conditions: The positive ion voltage is 300~400V, and the negative ion voltage is -300~-400V; Gas temperature is 350-450℃; The ionized gas is helium, and the pressure is 0.50 MPa; The standby gas is nitrogen with a pressure of 0.50 MPa; Injection parameters: The injection mode is 12-Dip-It Samplers mode; Sampling was performed by spot sampling with a sample volume of 3 to 5 μL; The injection speed is 0.6 mm / s; (4) Using high-resolution mass spectrometry, based on positive and negative ion modes, data-dependent secondary ion full scan (Full MS, Intensity, Dynamic Exclusion, Targeted Mass, ddMS2) scanning mode; Full MS parameters: scan range 100-1000, resolution 70000; dd-MS 2 Parameters: resolution 17500, normalized collision energy (NCE) 20, 40, 60, 80 eV, where the NCE of ciclopirox is 80 eV; (5) Data processing: Extract the primary mass spectra and secondary mass spectra of 120 anti-infective drugs from the standard substance collection data, and determine the accurate mass of the parent ion and secondary mass spectrum fragment ion of each substance of the 120 anti-infective drugs; Extract sample collection data, extract primary mass spectra, and preliminarily and quickly screen out anti-infective drugs in cosmetics. At the same time, extract secondary mass spectra for the screened anti-infective drugs, and combine them with secondary characteristic ions for further confirmation to achieve accurate characterization.

2. The detection method according to claim 1, wherein In the mixed series of standard working solutions of 120 anti-infective drugs described in step (1), the concentration of each standard substance is one or more concentrations between 10 and 5000 ng / mL.

3. The detection method according to claim 1, wherein The acetonitrile dilution ratio of the cosmetic to be tested in step (2) is 2 to 200 mg / mL. Preferably, the acetonitrile dilution ratio of the cosmetic to be tested in step (2) is 20 mg / mL.

4. The detection method according to claim 1, wherein The ultrasonic time in step (2) is 15 minutes.

5. The detection method according to claim 1, wherein The separation in step (2) is centrifugal separation or filtration separation.

6. The detection method according to claim 5, characterized in that The centrifugation condition is 5000 rpm for 5 min, and the filtration is microporous membrane filtration.

7. The detection method according to claim 1, characterized in that When the content of the substance to be tested is high, the step (2) further comprises diluting the supernatant with 80% methanol.

8. The detection method according to claim 1, wherein The injection speed in step (3) is 0.6 mm / s.

9. The detection method according to claim 1, wherein The setting of the secondary parent ion in the Targeted Mass in step (4) is:

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