Construction method of the fingerprint spectrum of serotonic capsule and application of the standard fingerprint spectrum

Abstract

The application provides a construction method of a Sairentong capsule fingerprint and application of a standard fingerprint thereof, and belongs to the technical field of drug detection. The construction method is that: first, a test sample solution and a control solution are prepared; then, acetonitrile is used as mobile phase A, and a 0.04wt%-0.06wt% phosphoric acid solution is used as mobile phase B; the test sample solution and the control solution are respectively detected by high performance liquid chromatography to obtain the fingerprint of the Sairentong capsule; and the standard fingerprint of the Sairentong capsule is obtained by using the construction method, and the standard fingerprint is used for quality evaluation or control in the whole process of research / development / production / clinical application of the Sairentong capsule. The construction method of the Sairentong capsule fingerprint can detect the main medicinal ingredient in the Sairentong capsule; and the provided standard fingerprint can provide a scientific basis for comprehensively establishing the quality control standard of the Sairentong capsule.

Description

Technical Field

[0001] This invention relates to drug detection technology, and more particularly to a method for constructing a fingerprint spectrum of siloxane capsules and the application of its standard fingerprint spectrum. Background Technology

[0002] Seruotong capsules are a traditional Chinese medicine compound formulated by extracting effective components from ginseng, ginkgo leaves and saffron, and combining them with modern pharmacological research. It has the effects of invigorating qi and blood circulation, and improving brain function and intelligence. It is mainly used to treat ischemic cerebrovascular diseases such as vascular dementia and the recovery period of ischemic stroke.

[0003] Characteristic chromatograms are chromatograms or spectra established for analyzing one or more classes of components in a substance. Currently, characteristic chromatograms have become an internationally recognized effective method for controlling the quality of traditional Chinese medicine (TCM) or natural drugs, and are a hot topic in the TCM field. In recent years, it has been gradually recognized that quality control methods targeting only a single chemical component are no longer adequate to reflect the intrinsic quality of a product. Characteristic chromatograms of TCM, as a multi-indicator quality control model, can better control the intrinsic quality of products. Therefore, constructing a fingerprint chromatogram for Seronotong capsules is particularly important for the quality control of Seronotong capsules.

[0004] Currently, existing technologies only include chromatographic analysis studies on Ginkgo biloba extract, saffron extract, and ginseng extract. For example, the paper "HPLC-DAD-ELSD Fingerprint Study of Ginkgo Biloba Extract" (https: / / www.doc88.com / p-2728211910840.html?r=1) discloses the use of acetonitrile-methanol-formic acid as a mobile phase to obtain the fingerprint spectrum of Ginkgo biloba extract; and the paper "Establishment of HPLC Fingerprint Spectrum and Component Analysis of Saffron" (https: / / www.cnki.com.cn / Article / CJFDTotal-ZCYA201901028.htm) discloses the use of (0.2% acetic acid-acetonitrile)-methanol as a mobile phase to obtain the fingerprint spectrum of saffron extract. However, none of these studies disclose how to obtain the fingerprint spectrum of the complex-component Seronoton capsule. Summary of the Invention

[0005] To address the above problems, this invention provides a method for constructing a fingerprint spectrum of Seroton capsules, along with its standard fingerprint spectrum and applications.

[0006] To achieve the above objectives, the technical solution of the present invention is: a method for constructing a fingerprint spectrum of siloxane capsules, the method comprising the following steps:

[0007] 1) Preparation of test solution and reference solution

[0008] The test solution was prepared by taking the contents of a siloxane capsule, adding methanol solution, and then sonicating, adjusting the volume, and filtering.

[0009] The reference solution was prepared by dissolving rutin, crocin-I, and ginsenoside Rb1 reference standards in methanol and making up to volume.

[0010] 2) Take the test solution and the reference solution respectively and perform high performance liquid chromatography to detect the fingerprint of the Seroton capsule;

[0011] The mobile phase A for high-performance liquid chromatography detection is acetonitrile, and the mobile phase B is an aqueous solution of phosphoric acid with a concentration of 0.04wt%-0.06wt%.

[0012] The elution method used in the high-performance liquid chromatography detection is gradient elution.

[0013] Furthermore, the elution conditions for the gradient elution are as follows:

[0014] 0–2 min, 13% mobile phase A, 87% mobile phase B;

[0015] 2–5 min, 13% → 17% mobile phase A, 87% → 83% mobile phase B;

[0016] 5–8 min, 17% mobile phase A, 83% mobile phase B;

[0017] 8–10 min, mobile phase A 17% → 19%, mobile phase B 83% → 81%;

[0018] 10–13 min, 19% → 20% mobile phase A, 81% → 80% mobile phase B;

[0019] 13–14 min, 20% → 22% mobile phase A, 80% → 78% mobile phase B;

[0020] 14–18 min, 22% mobile phase A, 78% mobile phase B;

[0021] 18–21 min, 22% → 30% mobile phase A, 78% → 70% mobile phase B;

[0022] 21–24 min, 30% → 32% mobile phase A, 70% → 68% mobile phase B;

[0023] 24–28 min, 32% → 40% mobile phase A, 68% → 60% mobile phase B;

[0024] 28–30 min, 40% → 60% mobile phase A, 60% → 40% mobile phase B;

[0025] 30–31 min, 60% → 90% mobile phase A, 40% → 10% mobile phase B;

[0026] 31–36 min, 90% mobile phase A, 10% mobile phase B;

[0027] 36–37 min, 90% → 13% mobile phase A, 10% → 87% mobile phase B;

[0028] 37–50 min, 13% mobile phase A, 87% mobile phase B.

[0029] Furthermore, the detection wavelength of the high-performance liquid chromatography is 203 nm or 254 nm.

[0030] Furthermore, the chromatographic column used for the high-performance liquid chromatography detection is an octadecylsilane-bonded silica column.

[0031] Furthermore, the column temperature for the high-performance liquid chromatography detection is 28-32℃, and the flow rate is 0.35-0.45 ml / min.

[0032] Furthermore, the methanol solution used in preparing the test solution is a 50% (v / v) methanol aqueous solution.

[0033] The fingerprint spectrum of Seruotong capsules obtained using the above construction method is used in the quality evaluation or control of the entire process of research / development / production / clinical application of Seruotong capsules. The obtained standard fingerprint spectrum is a standard fingerprint spectrum under the wavelength of 203nm, which includes 7 common characteristic peaks. Taking ginsenoside Rb1 (No. 3) as the reference peak, the relative retention times of the common peaks are as follows: Peak 1: 0.713±10%, Peak 2: 0.917±10%, Peak 3: 1.000±10%, Peak 4: 1.022±10%, Peak 5: 1.030±10%, Peak 6: 1.042±10%, Peak 7: 1.084±10%.

[0034] Furthermore, peak 1 is ginsenoside Rg1, peak 2 is ginsenoside Rf, peak 3 is ginsenoside Rb1, peak 4 is ginsenoside Rc, peak 5 is ginsenoside Ro, and peak 7 is ginsenoside Rd.

[0035] The application of the fingerprint spectrum of serlotinib capsules obtained using the above construction method in the quality evaluation or control of the entire process of research / development / production / clinical application of serlotinib capsules is characterized by the fact that the obtained standard fingerprint spectrum is a standard fingerprint spectrum under the wavelength condition of 254nm, including 16 common characteristic peaks, with rutin (peak 7) as the reference peak. The relative retention times of the common characteristic peaks are as follows: peak 1: 0.738±10%, peak 2: 0.751±10%, peak 3: 0.789±10%, peak 4: 0.868±10%. 10%, Peak 5: 0.893±10%, Peak 6: 0.925±10%, Peak 7: 1.000±10%, Peak 8: 1.339±10%, Peak 9: 1.381±10%, Peak 10: 1.489±10%, Peak 11: 1.757±10%, Peak 12: 2.127±10%, Peak 13: 2.217±10%, Peak 14: 2.558±10%, Peak 15: 2.752±10%, Peak 16: 3.484±10%.

[0036] Furthermore, peak 5 is kaempferol-3-O-β-D-sophoroside, peak 7 is rutin, peak 9 is kaempferol-3-O-rutinoside, peak 13 is crocin-I, peak 15 is crocin-II, and peak 16 is crocin-III.

[0037] The beneficial effects of the method for constructing the fingerprint spectrum of siloxane capsules, the standard fingerprint spectrum, and its application are as follows:

[0038] This invention achieves effective separation of different active ingredients in siloxane capsules by altering the elution system and utilizing the varying physicochemical properties of the different active ingredients. This is achieved by changing their flow rates within the chromatographic column. Furthermore, by adjusting the mobile phase composition, this invention yields a standard fingerprint chromatogram with good resolution, a stable baseline, numerous peaks, and a more accurate reflection of the quality of siloxane capsules. By selecting appropriate chromatographic columns, detection wavelengths, elution gradients, and other process conditions, this invention effectively optimizes the separation conditions, thereby improving the peak stability of the siloxane capsule standard fingerprint chromatogram. The construction method of this invention also demonstrates good feasibility, stability, and reproducibility.

[0039] The standard fingerprint spectrum of Seruotong capsules obtained by this invention has 7 common characteristic peaks at 203 nm wavelength and 16 chromatographic peaks at 254 nm wavelength. This provides effective assurance for quality monitoring of Seruotong capsules throughout the research, development, production, and clinical application processes. By utilizing the presence and characteristics of common characteristic peaks in the standard fingerprint spectrum of Seruotong capsules obtained by this invention, the quality of raw materials, semi-finished products, and finished products of Seruotong capsules can be monitored. By comparing the similarity of chromatographic fingerprint characteristics, the quality, stability, and consistency of Seruotong capsules can be evaluated, thus compensating for the deficiencies of current quality control methods. At the same time, the stability of the production process of Seruotong capsules can also be monitored, ensuring the stability, uniformity, and controllability of its quality. Attached Figure Description

[0040] The present invention will now be described in further detail with reference to the accompanying drawings and specific embodiments.

[0041] Figure 1 These are the fingerprint spectra of each sample under the 203nm detection condition in Example 7 of this invention;

[0042] Figure 2 These are the fingerprint spectra of each sample under the 254nm detection condition in Example 7 of this invention;

[0043] Figure 3 This is the standard fingerprint spectrum under the 203nm detection condition in Embodiment 7 of the present invention;

[0044] Figure 4 This is the standard fingerprint spectrum under the 254nm detection condition in Embodiment 7 of the present invention;

[0045] Figure 5 This is the UPLC image of the overall fingerprint spectrum of Seruotong capsules (203nm) in Experimental Example 1 of the present invention. From bottom to top, the images are blank, corn starch, silicon dioxide, ginsenoside Rb1 and Seruotong capsules-2010111.

[0046] Figure 6 This is the UPLC image of the overall fingerprint spectrum of Seroton capsules (254nm) in Experimental Example 1 of the present invention. From bottom to top, the images are blank, corn starch, silica, rutin and Seroton capsules-2010111.

[0047] Figure 7 This is a comparison of the repeatability of the fingerprint spectrum of Seroton capsules (203nm) in Experimental Example 1 of the present invention by UPLC. The repeatability is 1-6 from bottom to top in the figure.

[0048] Figure 8This is a comparison of the repeatability of the fingerprint spectrum of Seroton capsules (254nm) in Experimental Example 1 of the present invention by UPLC. The repeatability is 1-6 from bottom to top in the figure.

[0049] Figure 9 This is a UPLC comparison of the fingerprint stability of Seroton capsules (203nm) in Experimental Example 1 of the present invention. The chromatograms from bottom to top in the figure are the chromatograms of stability at 0h, 8h, 16h, 24h, 32h, 40h and 48h.

[0050] Figure 10 This is a UPLC comparison of the fingerprint stability of Seroton capsules (254nm) in Experimental Example 1 of the present invention. The chromatograms of stability at 0h, 8h, 16h, 24h, 32h, 40h and 48h are shown from bottom to top in the figure.

[0051] Figure 11 This is a comparison of intermediate precision UPLC fingerprint spectra of Seroton capsules (203nm) in Experiment Example 1 of the present invention. The intermediate precision is 1 to 6 from bottom to top in the figure.

[0052] Figure 12 This is a comparison of intermediate precision UPLC fingerprint spectra of Seroton capsules (254nm) in Experiment Example 1 of the present invention. The intermediate precision is 1 to 6 from bottom to top in the figure.

[0053] Figure 13 This is a UPLC comparison of the robustness of the fingerprint spectrum of Seronoton capsules (203nm) in Experimental Example 1 of this invention (at different flow rates). The flow rates from bottom to top in the figure are 0.35ml / min, 0.40ml / min, and 0.45ml / min.

[0054] Figure 14 This is a UPLC comparison of the robustness of the fingerprint spectrum of Seronoton capsules (254nm) in Experimental Example 1 of this invention (at different flow rates). The flow rates from bottom to top in the figure are 0.35ml / min, 0.40ml / min, and 0.45ml / min.

[0055] Figure 15 This is a UPLC comparison of the robustness of the fingerprint spectrum of Seroton capsules (203nm) in Experimental Example 1 of this invention (at different column temperatures). The temperatures in the figure from bottom to top are 28℃, 30℃ and 32℃.

[0056] Figure 16 This is a UPLC comparison of the robustness of the fingerprint spectrum of Seroton capsules (254nm) in Experiment Example 1 of this invention (at different column temperatures). The temperatures in the figure are 28℃, 30℃ and 32℃ from bottom to top.

[0057] Figure 17This is a UPLC comparison of the robustness of the fingerprint spectrum (at different acidities) of Seroton capsules (203nm) in Experimental Example 1 of this invention. The acidities from bottom to top in the figure are 0.04% phosphoric acid, 0.05% phosphoric acid, and 0.06% phosphoric acid.

[0058] Figure 18 This is a UPLC comparison of the robustness of the fingerprint spectrum (at different acidities) of Seroton capsules (254nm) in Experimental Example 1 of this invention. The acidities from bottom to top in the figure are 0.04% phosphoric acid, 0.05% phosphoric acid, and 0.06% phosphoric acid.

[0059] Figure 19 This is a UPLC comparison chart of the robustness of the fingerprint spectrum of Seroton capsules (203nm) in Experimental Example 1 of this invention (different chromatographic columns). The column models from bottom to top in the chart are 138#, 150#, and 158#.

[0060] Figure 20 This is a UPLC comparison chart of the robustness of the fingerprint spectrum of Seroton capsules (254nm) in Experimental Example 1 of this invention (different chromatographic columns). The column models from bottom to top in the chart are 138#, 150#, and 158#.

[0061] Figure 21 This refers to the fingerprint spectrum similarity (reproducibility) of the Seroton capsule (203nm) in Experimental Example 2 of this invention;

[0062] Figure 22 This refers to the fingerprint spectrum similarity (reproducibility) of the Seroton capsule (254nm) in Experimental Example 2 of this invention;

[0063] Figure 23 The fingerprint spectrum similarity (stability) of the Seroton capsule (203nm) in Experimental Example 2 of this invention;

[0064] Figure 24 This refers to the similarity (stability) of the fingerprint spectrum of the Seroton capsule (254nm) in Experimental Example 2 of this invention;

[0065] Figure 25 This refers to the fingerprint similarity (intermediate precision) of the Seroton capsule (203nm) in Experimental Example 2 of this invention;

[0066] Figure 26 This refers to the fingerprint similarity (intermediate precision) of the Seroton capsule (254nm) in Experimental Example 2 of this invention;

[0067] Figure 27 The fingerprint similarity (durability - different flow rates) of the Seroton capsule (203nm) in Experimental Example 2 of this invention;

[0068] Figure 28The fingerprint spectrum similarity (durability - different flow rates) of the siloxane capsules (254nm) in Experimental Example 2 of this invention;

[0069] Figure 29 The fingerprint spectrum similarity (durability - different column temperatures) of the Seroton capsule (203nm) in Experimental Example 2 of this invention;

[0070] Figure 30 The fingerprint spectrum similarity (durability - different column temperatures) of the Seroton capsule (254nm) in Experimental Example 2 of this invention;

[0071] Figure 31 This is the fingerprint spectrum similarity (durability - different acidity) of the Seroton capsules (203nm) in Experimental Example 2 of this invention;

[0072] Figure 32 This is the fingerprint spectrum similarity (durability - different acidity) of the Seroton capsules (254nm) in Experimental Example 2 of this invention;

[0073] Figure 33 The fingerprint spectrum similarity (robustness - different chromatographic columns) of Seroton capsules (203nm) in Experimental Example 2 of this invention;

[0074] Figure 34 The fingerprint spectrum similarity (robustness - different chromatographic columns) of Seroton capsules (254nm) in Experimental Example 2 of this invention;

[0075] Figure 35 This is the chromatogram of Comparative Example 1 of the present invention;

[0076] Figure 36 This is a chromatogram of Seroton capsules, Ginkgo biloba extract and saffron extract in Comparative Example 2 of the present invention. From bottom to top, the chromatogram represents Seroton capsules, Ginkgo biloba extract and saffron extract respectively.

[0077] Figure 37 This is a chromatogram of Seruotong capsules, ginseng extract and ginsenoside reference standard in Comparative Example 2 of the present invention. From bottom to top, the figures represent ginseng extract, ginsenoside reference standard and Seruotong capsules, respectively.

[0078] Figure 38 This is a chromatogram of the mobile phase changed in Comparative Example 3 of the present invention. From bottom to top, the chromatogram represents Ginkgo biloba extract, saffron extract, and Seroton capsules.

[0079] Figure 39 This is a chromatogram of the mobile phase changed in Comparative Example 3 of the present invention. From bottom to top, the chromatogram represents ginseng extract, siluotong capsules, and ginsenoside reference standard.

[0080] Figure 40This is a chromatogram of the gradient elution program changed in Comparative Example 4 of the present invention. The figure shows the chromatograms of two Seronoton capsule samples. Detailed Implementation

[0081] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Many specific details are set forth in the following description to provide a thorough understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art can make similar extensions without departing from the spirit of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0082] Example 1: A method for constructing a fingerprint spectrum of siloxane capsules

[0083] In this embodiment, the fingerprint spectrum was constructed using Seroton capsules produced by Shenwei Pharmaceutical. The construction method includes the following steps:

[0084] 1) Preparation of test solution and reference solution

[0085] Preparation of the test solution: Take 10 capsules of Seronoton, pour out the contents, mix well, take about 50mg, accurately weigh it, put it in a 25ml volumetric flask, add an appropriate amount of 50% methanol, stopper tightly, sonicate for 10 minutes, take it out, let it cool, make up the lost weight with 50% methanol, shake well, filter, and take the filtrate to obtain the test solution.

[0086] Preparation of reference solutions: Take appropriate amounts of rutin, crocin-I, and ginsenoside Rb1 reference standards, accurately weigh them, and add methanol to prepare solutions containing 30 μg per ml.

[0087] 2) Inject 2 μl of each of the test solution and the reference solution into the liquid chromatograph for high performance liquid chromatography detection, record the chromatogram, and obtain the fingerprint chromatogram of the Seroton capsule;

[0088] The mobile phase A for high-performance liquid chromatography (HPLC) detection is acetonitrile, and the mobile phase B is a 0.05 wt% aqueous solution of phosphoric acid. The elution method for HPLC detection is gradient elution, the detection wavelength is 203 nm, the chromatographic column is an octadecylsilane-bonded silica column, the column temperature is 30 °C, and the flow rate is 0.40 ml / min. The theoretical plate number, calculated based on the ginsenoside Rb1 peak, should not be less than 5000.

[0089] The elution conditions for the gradient elution are as follows:

[0090] 0–2 min, 13% mobile phase A, 87% mobile phase B;

[0091] 2–5 min, 13% → 17% mobile phase A, 87% → 83% mobile phase B;

[0092] 5–8 min, 17% mobile phase A, 83% mobile phase B;

[0093] 8–10 min, mobile phase A 17% → 19%, mobile phase B 83% → 81%;

[0094] 10–13 min, 19% → 20% mobile phase A, 81% → 80% mobile phase B;

[0095] 13–14 min, 20% → 22% mobile phase A, 80% → 78% mobile phase B;

[0096] 14–18 min, 22% mobile phase A, 78% mobile phase B;

[0097] 18–21 min, 22% → 30% mobile phase A, 78% → 70% mobile phase B;

[0098] 21–24 min, 30% → 32% mobile phase A, 70% → 68% mobile phase B;

[0099] 24–28 min, 32% → 40% mobile phase A, 68% → 60% mobile phase B;

[0100] 28–30 min, 40% → 60% mobile phase A, 60% → 40% mobile phase B;

[0101] 30–31 min, 60% → 90% mobile phase A, 40% → 10% mobile phase B;

[0102] 31–36 min, 90% mobile phase A, 10% mobile phase B;

[0103] 36–37 min, 90% → 13% mobile phase A, 10% → 87% mobile phase B;

[0104] 37–50 min, 13% mobile phase A, 87% mobile phase B.

[0105] Meanwhile, a reference standard for the main ingredient in Seroton capsules was selected for identification studies. The information on the reference standard is shown in Table 1.

[0106] Table 1. Reference Standard Information

[0107]

[0108]

[0109] Methods for constructing fingerprint spectra of Seroton capsules (Examples 2-6)

[0110] Examples 2-6 are methods for constructing fingerprint chromatograms of siloxane capsules. Their steps are basically the same as in Example 1, the difference being the different high-performance liquid chromatography (HPLC) detection parameters, as detailed in Table 2.

[0111] Table 2. Summary of process parameters in Examples 2-6

[0112]

[0113] Specifically, when the detection wavelength is 254nm, the theoretical plate number calculated based on the rutin peak should be no less than 5000; when the detection wavelength is 203nm, the theoretical plate number calculated based on the ginsenoside Rb1 peak should be no less than 5000.

[0114] Example 7: Standard fingerprint spectrum of Seroton capsules

[0115] Using the fingerprint chromatogram construction method for Seruotong capsules in Example 1, the fingerprint chromatograms of six batches of Seruotong capsule samples were determined under 203 nm or 254 nm conditions. Under the 203 nm detection condition, the chromatogram of ginsenoside Rb1 showed good resolution, good peak shape, and moderate retention time, and was therefore labeled as peak S. Ginsenoside Rb1 standard was also used as a reference. Under the 254 nm detection condition, the chromatogram of rutin showed good resolution, good peak shape, and moderate retention time, and was therefore labeled as peak S. Rutin standard was also used as a reference.

[0116] The chromatographic peaks with good stability and suitable response values ​​in the fingerprint spectra of these 6 batches of samples were taken as common peaks, and a total of 7 common peaks were identified at a detection wavelength of 203 nm. Figure 1 ), Figure 1 Peaks with the same component in the common peaks of different batches of samples were connected by dashed lines, with each dashed line representing peak 1 through peak 7 from left to right; a total of 16 common peaks were identified at a detection wavelength of 254 nm. Figure 2 ), Figure 2 Connect the peaks with the same component in the common peaks of different batches of samples with dashed lines. The dashed lines are peaks 1-16 from left to right.

[0117] The fingerprint spectra of the above six batches of Seruotong capsules were automatically matched using the "Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine (2012 Edition)" issued by the National Pharmacopoeia Commission to form a common pattern diagram. Standard fingerprint spectra of Seruotong capsules under 203 nm and 254 nm conditions were obtained, as shown below. Figure 3 and Figure 4 As shown;

[0118] The relative retention times of each common peak are:

[0119] The standard fingerprint spectrum at a wavelength of 203 nm includes 7 common characteristic peaks. Taking ginsenoside Rb1 (No. 3) as the reference peak, the relative retention times of the common peaks are as follows: Peak 1: 0.713±10%, Peak 2: 0.917±10%, Peak 3: 1.000±10%, Peak 4: 1.022±10%, Peak 5: 1.030±10%, Peak 6: 1.042±10%, Peak 7: 1.084±10%.

[0120] The standard fingerprint spectrum at 254 nm wavelength includes 16 common characteristic peaks. Taking rutin (peak 7) as the reference peak, the relative retention times of the common characteristic peaks are as follows: Peak 1: 0.738±10%, Peak 2: 0.751±10%, Peak 3: 0.789±10%, Peak 4: 0.868±10%, Peak 5: 0.893±10%, Peak 6: 0.925±10%, Peak 7: [The remaining text appears to be incomplete and requires further context.] Peak 8: 1.000±10%, Peak 9: 1.339±10%, Peak 10: 1.489±10%, Peak 11: 1.757±10%, Peak 12: 2.127±10%, Peak 13: 2.217±10%, Peak 14: 2.558±10%, Peak 15: 2.752±10%, Peak 16: 3.484±10%. Similar to Example 1, the main component reference standard of the siloxane capsules was selected for component identification, and the results are shown in Tables 3 and 4.

[0121] Table 3

[0122] 1 Ginsenoside Rg1 2 Ginsenoside Rf 3(S) Ginsenoside Rb1 4 Ginsenoside Rc 5 Ginsenoside Ro 6 6 7 Ginsenoside Rd

[0123] Table 4

[0124] 1 1 2 2 3 3 4 4 5 Kaempferol-3-O-β-D-sophoroside 6 6 7(S) Rutin 8 8 9 Kaempferol-3-O-rutin 10 10 11 11 12 12 13 Saffron glycoside-I 14 14 15 Saffron glycoside-II 16 Saffron glycoside-III

[0125] Experiment Example 1: Investigation of Fingerprint Mapping Methodology

[0126] This experimental example examines the construction method of the fingerprint spectrum of Seroton capsule in Example 1, mainly focusing on the repeatability, stability, intermediate precision, and robustness of the construction method.

[0127] 1. Specificity test and holistic investigation

[0128] Take 10 capsules of Celosia capsules (batch number: 2010111), pour out the contents, mix well, take approximately 50 mg, accurately weigh, and operate according to the preparation method and determination method of the test solution determined in the examples, extending the detection time by 30 minutes. The overall performance of the excipient corn starch (27.5 mg, prepared by the same method), excipient silica (6.25 mg, adjusted to 250 ml), blank solvent, reference standard, and test sample was investigated. The results are as follows: Figure 5 and Figure 6 As shown in the figure, the excipients corn starch, silica, and blank solvent do not interfere with each other, indicating good specificity; there are no chromatographic peaks within the extended 30-minute period, indicating good overall consistency.

[0129] 2. Repeatability test

[0130] Take 10 capsules of Celosia capsules (batch number: 2010111), pour out the contents, mix well, and take approximately 50 mg (6 portions in total), accurately weigh them, and operate according to the preparation method and determination method of the test solution determined in Example 1. Calculate the relative retention time of the common peak. The results are as follows: Figure 7 , Figure 8 As shown in Tables 5 and 6.

[0131] Table 5. Summary of Relative Retention Time Repeatability of Seroton Capsules (203nm) Fingerprint (n=6)

[0132] 1 Ginsenoside Rg1 0.713 0.713 0.713 0.714 0.713 0.712 0.713 0.09 2 Ginsenoside Rf 0.917 0.916 0.917 0.916 0.917 0.916 0.917 0.06 3(S) Ginsenoside Rb1 1.000 1.000 1.000 1.000 1.000 1.000 1.000 0 4 Ginsenoside Rc 1.022 1.022 1.022 1.022 1.022 1.022 1.022 0 5 Ginsenoside Ro 1.030 1.030 1.030 1.030 1.030 1.030 1.030 0 6 6 1.042 1.042 1.042 1.042 1.042 1.042 1.042 0 7 Ginsenoside Rd 1.084 1.084 1.084 1.084 1.084 1.084 1.084 0

[0133] Table 6. Summary of Relative Retention Time Repeatability of Seroton Capsules (254nm) Fingerprint (n=6)

[0134] 1 1 0.738 0.737 0.738 0.739 0.738 0.737 0.738 0.10 2 2 0.751 0.750 0.751 0.752 0.751 0.750 0.751 0.10 3 3 0.789 0.788 0.789 0.790 0.789 0.788 0.789 0.10 4 4 0.868 0.868 0.868 0.868 0.868 0.868 0.868 0 5 Kaempferol-3-O-β-D-sophoroside 0.892 0.893 0.893 0.893 0.893 0.892 0.893 0.06 6 6 0.924 0.925 0.924 0.925 0.925 0.925 0.925 0.06 7(S) Rutin 1.000 1.000 1.000 1.000 1.000 1.000 1.000 0 8 8 1.339 1.340 1.339 1.339 1.340 1.338 1.339 0.06 9 Kaempferol-3-O-rutin 1.381 1.382 1.381 1.381 1.381 1.380 1.381 0.05 10 10 1.489 1.490 1.489 1.489 1.489 1.488 1.489 0.04 11 11 1.757 1.758 1.757 1.757 1.757 1.755 1.757 0.06 12 12 2.127 2.128 2.127 2.128 2.126 2.125 2.127 0.05 13 Saffron glycoside-I 2.217 2.219 2.216 2.218 2.215 2.215 2.217 0.07 14 14 2.559 2.560 2.556 2.560 2.556 2.555 2.558 0.09 15 Saffron glycoside-II 2.753 2.754 2.752 2.751 2.75 2.751 2.752 0.05 16 Saffron glycoside-III 3.485 3.487 3.484 3.483 3.482 3.485 3.484 0.05

[0135] The results showed that the relative retention times of the common peaks were not significantly different, and the RSDs were all less than 5%, indicating good repeatability.

[0136] 3. Stability test

[0137] Take 10 capsules of Celosia capsules (batch number: 2010111), pour out the contents, mix well, take approximately 50 mg, accurately weigh it, and operate according to the preparation method and determination method of the test solution determined in Example 1. Inject the sample for determination at 0, 8, 16, 24, 32, 40, and 48 hours after preparation. Calculate the relative retention time of the common peak. The results are as follows. Figure 9 , Figure 10 As shown in Tables 7 and 8.

[0138] Table 7 Summary of relative retention times of the fingerprint spectrum stability of Seroton capsules (203nm) (n=7)

[0139] 1 Ginsenoside Rg1 0.702 0.701 0.699 0.700 0.698 0.697 0.697 0.699 0.28 2 Ginsenoside Rf 0.915 0.915 0.915 0.915 0.915 0.915 0.915 0.915 0 3(S) Ginsenoside Rb1 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 0 4 Ginsenoside Rc 1.023 1.022 1.023 1.023 1.023 1.023 1.023 1.023 0.04 5 Ginsenoside Ro 1.030 1.030 1.030 1.030 1.031 1.031 1.031 1.030 0.05 6 6 1.042 1.043 1.043 1.043 1.043 1.043 1.043 1.043 0.04 7 Ginsenoside Rd 1.085 1.085 1.085 1.085 1.086 1.086 1.086 1.085 0.05

[0140] Table 8. Summary of relative retention times of the fingerprint spectrum stability of Seroton capsules (254nm) (n=7)

[0141] 1 1 0.735 0.734 0.734 0.736 0.736 0.736 0.737 0.735 0.15 2 2 0.749 0.749 0.749 0.750 0.751 0.751 0.751 0.750 0.13 3 3 0.788 0.788 0.789 0.790 0.790 0.790 0.791 0.789 0.14 4 4 0.869 0.869 0.870 0.869 0.871 0.870 0.870 0.870 0.09 5 Kaempferol-3-O-β-D-sophoroside 0.894 0.894 0.895 0.895 0.896 0.896 0.896 0.895 0.10 6 6 0.926 0.926 0.926 0.926 0.927 0.927 0.927 0.926 0.06 7(S) Rutin 1.000 1.000 1.000 1.000 1.000 1.000 1.000 1.000 0 8 8 1.334 1.334 1.332 1.332 1.330 1.328 1.328 1.331 0.19 9 Kaempferol-3-O-rutin 1.379 1.379 1.377 1.377 1.376 1.373 1.374 1.376 0.17 10 10 1.491 1.492 1.491 1.490 1.490 1.488 1.489 1.490 0.09 11 11 1.761 1.763 1.762 1.761 1.762 1.761 1.760 1.761 0.06 12 12 2.147 2.152 2.154 2.149 2.153 2.155 2.154 2.152 0.14 13 Saffron glycoside-I 2.235 2.240 2.240 2.237 2.241 2.241 2.241 2.239 0.11 14 14 2.569 2.574 2.571 2.569 2.571 2.571 2.570 2.571 0.07 15 Saffron glycoside-II 2.795 2.801 2.803 2.798 2.805 2.807 2.808 2.802 0.17 16 Saffron glycoside-III 3.553 3.562 3.570 3.561 3.572 3.576 3.577 3.567 0.25

[0142] The results showed that the relative retention times of the common peaks were not significantly different, and the RSDs were all less than 10%, indicating good stability of the test sample solution within 48 hours.

[0143] 4. Intermediate precision test

[0144] Take 10 capsules of Celosia capsules (batch number: 2010111), pour out the contents, mix well, and take approximately 50 mg (6 portions in total), accurately weigh them, change the instrument, and operate according to the preparation method and determination method of the test solution determined in Example 1. Calculate the relative retention time of its common peak, and the results are as follows: Figure 11 , Figure 12 As shown in Tables 9 and 10.

[0145] Table 9 Summary of intermediate precision and relative retention time of Seroton Capsules (203nm) fingerprint spectrum (n=6)

[0146]

[0147]

[0148] Table 10 Summary of intermediate precision and relative retention time of Seroton capsule (254nm) fingerprint spectrum (n=6)

[0149] 1 1 0.719 0.717 0.716 0.717 0.716 0.716 0.717 0.16 2 2 0.733 0.732 0.732 0.733 0.731 0.732 0.732 0.10 3 3 0.770 0.770 0.769 0.770 0.769 0.770 0.770 0.07 4 4 0.842 0.839 0.837 0.838 0.837 0.838 0.839 0.22 5 Kaempferol-3-O-β-D-sophoroside 0.874 0.872 0.871 0.872 0.871 0.871 0.872 0.13 6 6 0.911 0.909 0.908 0.909 0.908 0.908 0.909 0.13 7(S) Rutin 1.000 1.000 1.000 1.000 1.000 1.000 1.000 0 8 8 1.346 1.344 1.342 1.342 1.342 1.342 1.343 0.12 9 Kaempferol-3-O-rutin 1.381 1.379 1.377 1.377 1.376 1.377 1.378 0.13 10 10 1.474 1.472 1.469 1.469 1.468 1.470 1.470 0.15 11 11 1.741 1.736 1.733 1.735 1.732 1.734 1.735 0.18 12 12 2.066 2.056 2.050 2.055 2.050 2.052 2.055 0.29 13 Saffron glycoside-I 2.160 2.142 2.134 2.140 2.132 2.135 2.141 0.48 14 14 2.497 2.483 2.473 2.478 2.471 2.474 2.479 0.39 15 Saffron glycoside-II 2.590 2.569 2.557 2.560 2.554 2.557 2.565 0.53 16 Saffron glycoside-III 3.262 3.237 3.222 3.225 3.218 3.223 3.231 0.51

[0150] The results show that the relative retention times of the common peaks are not significantly different, and the RSDs are all less than 10%, indicating that the intermediate precision of this method is good.

[0151] 5. Durability test

[0152] This experiment investigated the robustness of three different flow rates, three different column temperatures, three different chromatographic columns, and three different acidities to the chromatographic conditions. Following the preparation and determination methods for the test solution as defined in Example 1, the relative retention times of the common peaks were calculated, and the results are as follows: Figure 13-20 As shown in Table 11-18.

[0153] Table 11 Summary of the relative retention time (at different flow rates) of the fingerprint spectrum robustness of Seroton capsules (203nm) (n=3)

[0154] 1 Ginsenoside Rg1 0.718 0.702 0.682 0.701 2.57 2 Ginsenoside Rf 0.924 0.916 0.909 0.916 0.82 3(S) Ginsenoside Rb1 1.000 1.000 1.000 1.000 0 4 Ginsenoside Rc 1.023 1.023 1.024 1.023 0.06 5 Ginsenoside Ro 1.033 1.031 1.030 1.031 0.15 6 6 1.042 1.043 1.045 1.043 0.15 7 Ginsenoside Rd 1.085 1.085 1.088 1.086 0.16

[0155] Table 12 Summary of the relative retention time (at different flow rates) of the fingerprint spectrum robustness of Seroton capsules (254nm) (n=3)

[0156]

[0157]

[0158] Table 13 Summary of relative retention times (at different column temperatures) of the fingerprint spectrum of Seroton capsules (203nm) (n=3)

[0159] 1 Ginsenoside Rg1 0.700 0.702 0.706 0.703 0.43 2 Ginsenoside Rf 0.917 0.916 0.915 0.916 0.11 3(S) Ginsenoside Rb1 1.000 1.000 1.000 1.000 0 4 Ginsenoside Rc 1.024 1.023 1.024 1.024 0.06 5 Ginsenoside Ro 1.033 1.031 1.030 1.031 0.15 6 6 1.044 1.043 1.044 1.044 0.06 7 Ginsenoside Rd 1.086 1.085 1.087 1.086 0.09

[0160] Table 14 Summary of relative retention times (at different column temperatures) of the fingerprint spectrum of Seroton capsules (254nm) (n=3)

[0161] 1 1 0.719 0.721 0.720 0.720 0.14 2 2 0.741 0.737 0.732 0.737 0.61 3 3 0.783 0.780 0.775 0.779 0.52 4 4 0.858 0.867 0.873 0.866 0.87 5 Kaempferol-3-O-β-D-sophoroside 0.885 0.892 0.899 0.892 0.78 6 6 0.915 0.925 0.934 0.925 1.03 7(S) Rutin 1.000 1.000 1.000 1.000 0 8 8 1.347 1.341 1.328 1.339 0.73 9 Kaempferol-3-O-rutin 1.388 1.387 1.378 1.384 0.40 10 10 1.493 1.501 1.505 1.500 0.41 11 11 1.759 1.770 1.776 1.768 0.49 12 12 2.137 2.160 2.186 2.161 1.13 13 Saffron glycoside-I 2.209 2.250 2.294 2.251 1.89 14 14 2.573 2.591 2.602 2.589 0.57 15 Saffron glycoside-II 2.765 2.822 2.889 2.825 2.20 16 Saffron glycoside-III 3.502 3.582 3.684 3.589 2.54

[0162] Table 15 Summary of the relative retention times (at different acidities) of the fingerprint spectrum of Seroton capsules (203nm) (n=3)

[0163]

[0164]

[0165] Table 16 Summary of the relative retention times (at different acidities) of the fingerprint spectrum of Seroton capsules (254nm) (n=3)

[0166] 1 1 0.721 0.721 0.723 0.722 0.16 2 2 0.737 0.737 0.739 0.738 0.16 3 3 0.780 0.780 0.781 0.780 0.07 4 4 0.866 0.867 0.867 0.867 0.07 5 Kaempferol-3-O-β-D-sophoroside 0.892 0.892 0.893 0.892 0.06 6 6 0.925 0.925 0.925 0.925 0 7(S) Rutin 1.000 1.000 1.000 1.000 0 8 8 1.341 1.341 1.341 1.341 0 9 Kaempferol-3-O-rutin 1.386 1.387 1.386 1.386 0.04 10 10 1.500 1.501 1.500 1.500 0.04 11 11 1.767 1.770 1.768 1.768 0.09 12 12 2.157 2.160 2.158 2.158 0.07 13 Saffron glycoside-I 2.247 2.250 2.248 2.248 0.07 14 14 2.586 2.591 2.587 2.588 0.10 15 Saffron glycoside-II 2.817 2.822 2.818 2.819 0.09 16 Saffron glycoside-III 3.577 3.582 3.576 3.578 0.09

[0167] Table 17 Summary of relative retention times (n=3) for the robustness of the fingerprint chromatograms of Seroton capsules (203nm) (different chromatographic columns)

[0168] 1 Ginsenoside Rg1 0.747 0.702 0.724 0.724 3.11 2 Ginsenoside Rf 0.926 0.916 0.924 0.922 0.57 3(S) Ginsenoside Rb1 1.000 1.000 1.000 1.000 0 4 Ginsenoside Rc 1.020 1.023 1.020 1.021 0.17 5 Ginsenoside Ro 1.030 1.031 1.029 1.030 0.10 6 6 1.040 1.043 1.041 1.041 0.15 7 Ginsenoside Rd 1.079 1.085 1.079 1.081 0.32

[0169] Table 18 Summary of relative retention times (n=3) for the robustness of the fingerprint chromatograms of Seroton capsules (254nm) (different chromatographic columns)

[0170]

[0171]

[0172] The results showed that the determination results were basically consistent under different flow rates, column temperatures, chromatographic columns, acidities, and instrument conditions. The common peaks in the chromatograms were sharp and symmetrical, with good resolution, and the relative retention times (RSD) were all less than 10%. This indicates that the method is robust to different flow rates, column temperatures, chromatographic columns, and acidities.

[0173] Experiment Example 2: Fingerprint Similarity Calculation

[0174] Similarity calculations were performed on the above fingerprint chromatograms. Specifically, a software system for evaluating the similarity of traditional Chinese medicine chromatographic fingerprint chromatograms was used. The similarity of repeatability, stability, intermediate precision, robustness, and control fingerprint chromatograms was calculated based on common peaks. The results are as follows: Figures 21-28 As shown. The similarity calculated based on the fingerprint chromatogram, the repeatability, stability, intermediate precision, and robustness compared to the reference fingerprint chromatogram are all greater than 0.90. Therefore, the fingerprint chromatogram can be selected as the evaluation standard. The test sample fingerprint chromatogram should show chromatographic peaks with the same retention times as the reference peaks. The test sample chromatogram should be substantially consistent with the reference fingerprint chromatogram, with a corresponding number of common peaks. According to the similarity evaluation system for traditional Chinese medicine chromatographic fingerprint chromatograms, the similarity is calculated based on common peaks. The similarity between the test sample fingerprint chromatogram and the reference fingerprint chromatogram should not be less than 0.90.

[0175] Comparative Example

[0176] Comparative Example 1

[0177] Based on Example 1, the 0.05 wt% phosphoric acid aqueous solution was replaced with a 0.05% formic acid aqueous solution, and the resulting chromatogram is shown below. Figure 35 As shown in the figure, it can be seen that the baseline of the chromatogram obtained after the mobile phase replacement is not stable, and the substances cannot be separated, indicating poor stability.

[0178] Comparative Example 2

[0179] Based on Example 1, ginsenosides, ginseng extract, saffron extract, and ginkgo leaf extract were simultaneously analyzed by high-performance liquid chromatography under the same chromatographic conditions. The results are as follows: Figure 36 , Figure 37 As shown in the figure, the peak shapes of the ginsenoside reference standard and the ginsenoside extract are basically the same. Ginkgo biloba extract also has a peak at the same point where ginsenoside Rg1 emerges, indicating that ginkgo biloba extract and ginseng extract may interfere with each other during chromatographic detection. However, the chromatographic conditions of this invention can effectively separate ginsenoside Rg1.

[0180] Comparative Example 3

[0181] Based on Example 1, the 0.05 wt% aqueous phosphoric acid solution was replaced with a 0.03 wt% aqueous phosphoric acid solution. Ginsenosides, ginseng extract, saffron extract, and ginkgo leaf extract were analyzed under the same chromatographic conditions as in this comparative example. The results are as follows: Figure 38 and Figure 39 As shown, although the baselines of each figure are relatively stable, the baselines of the peaks of each substance are not separated, and the separation effect is poor.

[0182] Comparative Example 4

[0183] Based on Example 1, the gradient elution conditions were changed, specifically:

[0184] 0–2 min, 13% mobile phase A, 87% mobile phase B;

[0185] 2–5 min, 13% → 15% mobile phase A, 87% → 85% mobile phase B;

[0186] 5–9 min, 15% → 20% mobile phase A, 85% → 80% mobile phase B;

[0187] 9–12 min, 20% mobile phase A, 80% mobile phase B;

[0188] 12–15 min, 20% → 22% mobile phase A, 80% → 78% mobile phase B;

[0189] 15–18 min, 22% mobile phase A, 78% mobile phase B;

[0190] 18–21 min, 22% → 30% mobile phase A, 78% → 70% mobile phase B;

[0191] 21–24 min, 30% → 33% mobile phase A, 70% → 67% mobile phase B;

[0192] 24–25 min, 33% mobile phase A, 67% mobile phase B;

[0193] 25–28 min, 33% → 60% mobile phase A, 67% → 40% mobile phase B;

[0194] 28–29 min, 60% → 90% mobile phase A, 40% → 10% mobile phase B;

[0195] 29–33 min, 90% mobile phase A, 10% mobile phase B;

[0196] 33–35 min, 90% → 13% mobile phase A, 10% → 87% mobile phase B;

[0197] 35–38 min, 13% mobile phase A, 87% mobile phase B.

[0198] The results are as follows Figure 40 As shown in the figure, the chromatograms of the two samples of the same Seroton capsules obtained under the same gradient elution conditions are quite different, indicating that changing the gradient elution program has a significant impact on the separation of each substance, and also indicates that the stability of this elution program is very poor.

[0199] In summary, the method for constructing the serosatin fingerprint spectrum of the present invention has high chromatographic stability, good stability and reproducibility.

[0200] Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

Claims

1. A method for constructing a fingerprint spectrum of siloxane capsules, characterized in that, The construction method includes the following steps: 1) Preparation of test solution and reference solution The test solution was prepared by taking the contents of a siloxane capsule, adding methanol solution, and then sonicating, adjusting the volume, and filtering. The reference solution was prepared by dissolving rutin, crocin-I, and ginsenoside Rb1 reference standards in methanol and making up to volume. 2) Take the test solution and the reference solution respectively and perform high performance liquid chromatography to obtain the fingerprint spectrum of the Seroton capsule; The mobile phase A for the high-performance liquid chromatography detection is acetonitrile, and the mobile phase B is an aqueous solution of phosphoric acid with a concentration of 0.04wt%-0.06wt%. The elution method for the high-performance liquid chromatography detection is gradient elution; The elution conditions for the gradient elution are as follows: 0–2 min, 13% mobile phase A, 87% mobile phase B; 2–5 min, 13% → 17% mobile phase A, 87% → 83% mobile phase B; 5–8 min, 17% mobile phase A, 83% mobile phase B; 8–10 min, mobile phase A 17% → 19%, mobile phase B 83% → 81%; 10–13 min, 19% → 20% mobile phase A, 81% → 80% mobile phase B; 13–14 min, 20% → 22% mobile phase A, 80% → 78% mobile phase B; 14–18 min, 22% mobile phase A, 78% mobile phase B; 18–21 min, 22% → 30% mobile phase A, 78% → 70% mobile phase B; 21–24 min, 30% → 32% mobile phase A, 70% → 68% mobile phase B; 24–28 min, 32% → 40% mobile phase A, 68% → 60% mobile phase B; 28–30 min, 40% → 60% mobile phase A, 60% → 40% mobile phase B; 30–31 min, 60% → 90% mobile phase A, 40% → 10% mobile phase B; 31–36 min, 90% mobile phase A, 10% mobile phase B; 36–37 min, 90% → 13% mobile phase A, 10% → 87% mobile phase B; 37–50 min, 13% mobile phase A, 87% mobile phase B; The detection wavelength for the high-performance liquid chromatography is 203 nm or 254 nm; The standard fingerprint spectrum of the Seroton capsule obtained by the construction method under a wavelength of 203 nm includes 7 common characteristic peaks. Taking ginsenoside Rb1 (No. 3) as the reference peak, the relative retention times of the common peaks are as follows: Peak 1: 0.713±10%, Peak 2: 0.917±10%, Peak 3: 1.000±10%, Peak 4: 1.022±10%, Peak 5: 1.030±10%, Peak 6: 1.042±10%, Peak 7: 1.084±10%. The standard fingerprint spectrum of the Seroton capsule obtained by the construction method, under a wavelength of 254 nm, includes 16 common characteristic peaks. Taking rutin (peak 7) as the reference peak, the relative retention times of the common characteristic peaks are as follows: Peak 1: 0.738±10%, Peak 2: 0.751±10%, Peak 3: 0.789±10%, Peak 4: 0.868±10%, Peak 5: 0.893±10%, Peak 6: 0.

92. Peak 5±10%, Peak 7: 1.000±10%, Peak 8: 1.339±10%, Peak 9: 1.381±10%, Peak 10: 1.489±10%, Peak 11: 1.757±10%, Peak 12: 2.127±10%, Peak 13: 2.217±10%, Peak 14: 2.558±10%, Peak 15: 2.752±10%, Peak 16: 3.484±10%; The chromatographic column used for high-performance liquid chromatography is an octadecylsilane-bonded silica column.

2. The method for constructing a fingerprint spectrum of a siloxane capsule according to claim 1, characterized in that, The column temperature for high-performance liquid chromatography (HPLC) detection is 28-32℃, and the flow rate is 0.35-0.45 ml / min.

3. The method for constructing a fingerprint spectrum of a siloxane capsule according to claim 1, characterized in that, The methanol solution used in preparing the test solution is a 50% (v / v) aqueous methanol solution.

4. The application of a fingerprint spectrum of serlotinib capsules obtained by the construction method described in any one of claims 1-3 in the quality evaluation or control of the entire process of research / development / production / clinical application of serlotinib capsules, characterized in that, The obtained standard fingerprint spectrum is a standard fingerprint spectrum under the wavelength condition of 203nm, which includes 7 common characteristic peaks. The peak 1 is ginsenoside Rg1, the peak 2 is ginsenoside Rf, the peak 3 is ginsenoside Rb1, the peak 4 is ginsenoside Rc, the peak 5 is ginsenoside Ro, and the peak 7 is ginsenoside Rd.

5. The application of a fingerprint spectrum of serlotinib capsules obtained by the construction method described in any one of claims 1-3 in the quality evaluation or control of the entire process of research / development / production / clinical application of serlotinib capsules, characterized in that, The obtained standard fingerprint spectrum is a standard fingerprint spectrum under the wavelength of 254 nm, which includes 16 common characteristic peaks. Peak 5 is kaempferol-3-O-β-D-sophoroside, peak 7 is rutin, peak 9 is kaempferol-3-O-rutinoside, peak 13 is crocin-I, peak 15 is crocin-II, and peak 16 is crocin-III.

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