Method and device for rapidly detecting main drug of Chenxianglubailu tablet based on surface enhanced Raman spectroscopy

Through the surface-enhanced Raman spectroscopy technology of fixing the SERS active substrate on the bottom of the glass centrifuge tube, the rapid, accurate and cost problems of bismuth nitrate detection in Chenxianglu white liu tablets were solved, and a simple and efficient detection effect was achieved.

CN120404698APending Publication Date: 2025-08-01SHANGHAI SINE WANXIANG PHARMA
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Patent Information

Application Number
CN202510808432.3
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2025-06-17
Publication Date
2025-08-01

AI Technical Summary

Technical Problem

In the prior art, the detection method for the second bismuth nitrate content of Chenxianglu white lilac tablets is cumbersome, time-consuming, susceptible to subjective factors of the operator, weak anti-interference ability, and modern instrument analysis methods are expensive and the sample pre-processing is complex, making it difficult to meet the fast, accurate and low-cost detection needs.

Method used

Using surface-enhanced Raman spectroscopy technology, the SERS active substrate is fixed at the bottom of the glass centrifuge tube, combined with simplified sample processing and spectral acquisition procedures, efficient and accurate determination of bismuth subnitrate content is achieved, and gold nanoparticle sol is used as the active substrate to simplify operation and improve detection speed.

Benefits of technology

It achieves efficient and accurate measurement of bismuth subnitrate content, is easy to operate, is cheap to cost, is not disturbed by complex matrix, has a fast detection speed, and is suitable for grassroots pharmaceutical companies and quality inspection institutions.

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Abstract

The invention belongs to the technical field of chemical analysis, and discloses a method and a device for rapidly detecting a main drug of a Chenxianglubailu tablet based on surface enhanced Raman spectroscopy, the detection method comprises the following steps: (1) providing a hemispherical glass centrifuge tube; (2) preparing gold nanoparticle sol with SERS (Surface Enhanced Raman Scattering) activity; (3) fixing the gold nanoparticle sol at the bottom of the glass centrifugal tube in a chemical bonding manner to form an SERS active substrate layer; and (4) pouring the sample solution containing the bismuth subnitrate molecules into a glass centrifuge tube, and then detecting by adopting a Raman spectrum analysis method. According to the method, the SERS active substrate is fixed at the bottom of the glass centrifugal tube, and simple sample treatment and spectrum acquisition processes are combined, so that the content of bismuth subnitrate is efficiently and accurately measured; a complicated micro-fluidic chip is not needed, the operation is simple and convenient, and the cost is low.
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Description

Technical Field

[0001] The present invention belongs to the technical field of chemical analysis, and relates to a method for detecting the main drugs of Chenxianglubailu tablets, in particular to a rapid detection method and device for the main drugs of Chenxianglubailu tablets based on surface-enhanced Raman spectroscopy. Background Art

[0002] Chenxianglubailu tablets are a kind of traditional Chinese medicine with the effects of strengthening the stomach and regulating the middle, regulating qi and relieving pain, and are widely used in clinical practice. Its main pharmacodynamic components include bismuth subnitrate (or basic bismuth nitrate), dried tangerine peel, licorice, etc. As one of the core main drug components of this preparation, the accurate and rapid determination of the content of bismuth subnitrate is directly related to the quality control, efficacy guarantee and drug safety of the medicine. Therefore, establishing an efficient and reliable method for detecting the main drug content is a key requirement in the links of drug production, circulation and supervision.

[0003] Currently, the legal detection method for the content of bismuth subnitrate in Chenxianglubailu tablets mainly relies on traditional quality standards such as (WS3-B-1553-93), and generally adopts the manual titration method (such as complexometric titration). The method of manually titrating to determine the content of bismuth subnitrate has many insurmountable limitations in practical applications, such as cumbersome operation, significant interference of excipients in different prescriptions on the color of the end-point titration, weak specificity, difficult judgment of the reaction end-point, long time-consuming, susceptible to the subjective factors of operators, and weak anti-interference ability, etc., and cannot meet the rapid detection requirements of modern pharmaceutical enterprises.

[0004] To solve the problems existing in the above-mentioned manual titration method, some modern instrumental analysis methods such as atomic absorption spectrometry (AAS) or inductively coupled plasma mass spectrometry (ICP-MS) can be used for the determination of bismuth element, which have the advantage of high sensitivity. However, these methods have expensive equipment, high operation and maintenance costs, are difficult to popularize in grass-roots pharmaceutical enterprises or quality inspection institutions, have complex sample pretreatment, may introduce pollution or loss, and can only determine the total bismuth content, and cannot specifically determine the form of bismuth subnitrate.

[0005] In summary, based on the urgent need for a rapid, specific and anti-interference detection technology for the main drug content of Chenxianglubailu tablets, the existing detection methods for the main drugs (bismuth subnitrate) of Chenxianglubailu tablets, whether traditional titration methods or some modern instrumental analysis methods, have obvious deficiencies in terms of rapidity, operation convenience, anti-interference ability of complex matrices, objectivity of end-point / result judgment, and on-site applicability.

[0006] Surface-enhanced Raman spectroscopy (SERS) technology has shown great potential in the rapid and in-situ detection of trace substances in complex matrices due to its extremely high sensitivity (reaching the single-molecule level), unique molecular fingerprint recognition ability, insensitivity to the aqueous environment, simple sample pretreatment, and fast detection speed (usually from a few seconds to dozens of seconds). This provides a highly promising new approach to solving the problem of rapid detection of the main drugs in Chenxianglubailu tablets. Summary of the Invention

[0007] To solve the above problems in the prior art, the present invention provides a rapid detection method and device for the main drugs in Chenxianglubailu tablets based on surface-enhanced Raman spectroscopy, which simplifies the fixing method of the SERS active substrate and the structure of the reaction device to achieve efficient and accurate determination of the bismuth subnitrate content.

[0008] To achieve the above object, the present invention adopts the following technical solutions:

[0009] The first aspect of the present invention is to provide a rapid detection method for the main drugs in Chenxianglubailu tablets based on surface-enhanced Raman spectroscopy, including the following steps:

[0010] (1) Provide a clean glass centrifuge tube with a hemispherical bottom for standby;

[0011] (2) Prepare a gold nanoparticle sol with SERS activity for standby;

[0012] (3) Fix the gold nanoparticle sol at the bottom of the glass centrifuge tube by a chemical bond method to form a SERS active substrate layer;

[0013] (4) Pour the sample solution containing bismuth subnitrate molecules into the glass centrifuge tube, and then perform detection by Raman spectroscopy analysis.

[0014] Preferably, in step (1), the glass centrifuge tube is a centrifuge tube with a hemispherical bottom, and the bottom thickness is 1 - 3 mm.

[0015] Preferably, in step (1), the top of the glass centrifuge tube is provided with a detachable rotating cap in a threaded manner, and a sealing gasket is provided at the inner top of the rotating cap.

[0016] Preferably, in step (2), the gold nanoparticle sol is one of gold or silver or copper nanospheres, gold or silver or copper octahedrons, gold or silver or copper nanorods, and gold or silver or copper tetradecahedrons.

[0017] Preferably, in step (2), the gold nanoparticle sol is prepared by a chemical reduction method (citric acid trisodium reduction method), and the specific preparation method is:

[0018] Heat 100 mL of ultrapure water to boiling, quickly add 1 mL of 1% chloroauric acid (HAuCl4) solution, stir evenly, then quickly add 10 mL of 1% sodium citrate solution, continue boiling and stirring until the solution color changes from orange-yellow to wine-red (about 15 minutes), and after cooling to room temperature, prepare a gold nanoparticle sol with a particle size of 60 - 80 nm.

[0019] Preferably, in step (3), first graft an amino group on the inner surface of the bottom of the glass centrifuge tube through a silanization reaction, and then firmly attach the gold nanoparticles by electrostatic adsorption to form a uniform SERS active layer.

[0020] Preferably, in step (3), by controlling the concentration of the gold nanoparticle sol (such as 1×10

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[0026] mol / L) and the placement time (12 hours), a uniform SERS active substrate layer with a thickness of about 50 - 100 nm can be formed (measured by scanning electron microscopy).

[0021] Preferably, in step (4), the preparation method of the sample solution is as follows:

[0022] Take 10 tablets of Chenxianglubailu tablets, grind them finely, accurately weigh 0.1 - 0.2 g (accurate to 0.0001 g), and place them in a 50 mL volumetric flask;

[0023] Add 20 mL of ethanol - water mixed solution (volume ratio 1:1), ultrasonically treat for 15 minutes (power 250 W, frequency 40 kHz), after cooling to room temperature, make up the volume to the scale with ethanol - water mixed solution, and shake well;

[0024] Take 10 mL of the solution, centrifuge at 3000 r / min for 5 minutes, and take the supernatant as the test solution (if it is turbid, it needs to be filtered).

[0025] Preferably, in step (4), the excitation wavelength of the Raman spectrum is 532 - 785 nm, the laser power is 1 - 10 mW, the integration time is 0.5 - 5 s, and the spectral range is 200 - 2000 cm -1 .

[0026] The second aspect of the present invention is to provide a hybrid reaction device prepared by using steps (1) - (3) in any one of the above rapid detection methods.

[0027] Adopting the above technical solutions, compared with the prior art, the present invention has the following technical effects:

[0028] The rapid detection method for the main drug of Chenxianglubailu tablets provided by the present invention realizes the efficient and accurate determination of the bismuth subnitrate content by fixing the SERS active substrate at the bottom of the glass centrifuge tube and combining a simple sample treatment and spectral acquisition process; moreover, the present invention does not require a complex microfluidic chip, is easy to operate, and has low cost. Brief Description of the Drawings

[0029] Figure 1 FIG. 1 is a schematic structural diagram of a simplified hybrid reaction device for the rapid detection method of the present invention;

[0030] Figure 2 FIG. 2 is a SERS characteristic spectrogram of bismuth subnitrate using the rapid detection method of the present invention. Detailed Description of the Invention

[0031] The present invention will be described in detail and specifically below through specific embodiments to better understand the present invention. However, the following embodiments do not limit the scope of the present invention.

[0032] Embodiment 1

[0033] A simplified hybrid reaction device for a rapid detection method is provided, as shown in FIG. 1. The simplified hybrid reaction device uses a clean glass centrifuge tube with a hemispherical bottom, and a SERS active substrate layer (gold nanoparticle layer) is fixed to the bottom of the glass centrifuge tube by chemical bonding. Figure 1 Among them, the glass centrifuge tube uses a centrifuge tube with a hemispherical bottom, as shown in FIG. 2. The hemispherical structural design enables the bottom of the centrifuge tube to have a certain area for adsorbing and fixing the SERS active substrate layer. And the bottom thickness of the glass centrifuge tube is 1-3 mm, preferably 2 mm.

[0034] The outer surface of the bottom of the glass centrifuge tube is treated with frosting to increase the friction during placement and prevent sliding; while the inner surface of the bottom is treated by a special process to be smooth and flat for fixing the SERS active substrate. When preparing the SERS active substrate layer on the bottom of the glass centrifuge tube, first graft an amino group on the inner surface of the bottom through a silanization reaction, and then firmly attach gold nanoparticles by electrostatic adsorption to form a uniform SERS active layer to ensure the stable enhancement of Raman signals. Figure 1

[0035]

[0036]

[0037] To ensure the accuracy of the detection results and avoid contamination of the sample by external impurities, a detachable rotary cap is provided with a threaded connection at the top of the glass centrifuge tube. The rotary cap has an internal thread, and a sealing gasket is embedded in the inner top of the rotary cap. The sealing gasket can be a polytetrafluoroethylene (PTFE) gasket. The thickness of the polytetrafluoroethylene (PTFE) gasket is 2-5 mm, preferably 3 mm. The PTFE material is soft and corrosion-resistant.

[0037] To enable removable installation of the rotating cap, the top of the glass centrifuge tube is provided with a precisely machined external thread with a pitch of 1.2mm, a thread depth of 0.5mm, and 10 complete turns. By tightening the internally threaded rotating cap onto the top of the glass centrifuge tube and utilizing a sealing gasket, a strong seal is formed, effectively preventing volatilization or leakage of the solution during oscillation and rest, ensuring rapid and stable testing.

[0038] When the screw cap is tightened, the PTFE gasket fits tightly against the top of the glass centrifuge tube, creating a seal that prevents volatilization or leakage of the solution during oscillation and resting, while also preventing contamination of the sample by external impurities, ensuring accurate test results. Concentrically arranged, raised anti-slip grooves can be added to the center of the screw cap to facilitate easy opening and closing.

[0039] Example 2

[0040] Based on the mixed reaction device shown in Example 1, a rapid detection method for the main drug of Chenxianglu Bailu tablets based on surface enhanced Raman spectroscopy is provided, which specifically includes the following steps:

[0041] (1) Provide a clean glass centrifuge tube with a hemispherical bottom for standby use;

[0042] (2) Heat 100 mL of ultrapure water to boiling, quickly add 1 mL of 1% chloroauric acid (HAuCl4) solution, stir evenly, and then quickly add 10 mL of 1% trisodium citrate solution. Continue boiling and stirring until the color of the solution changes from orange to wine red (about 15 minutes). After cooling to room temperature, a gold nanoparticle sol with a particle size of 60-80 nm is prepared and set aside.

[0043] (3) First, amino groups are grafted onto the inner surface of the bottom of the glass centrifuge tube by silanization reaction, and then the gold nanoparticles are firmly attached by electrostatic adsorption. At the same time, the concentration and placement time of the gold nanoparticle sol are controlled to form a uniform SERS active substrate layer with a thickness of about 50-100 nm; and a rotating cover and a sealing gasket are used for sealing to form a SERS substrate layer. Figure 1 The mixing reaction device shown;

[0044] (4) Pour the sample solution containing bismuth subnitrate molecules into the glass centrifuge tube, and then perform detection by Raman spectroscopy analysis; the preparation method of the sample solution is as follows: Take 10 tablets of Chenxianglubailu tablets, grind them finely, accurately weigh 0.1 - 0.2 g (accurate to 0.0001 g), and place them in a 50 mL volumetric flask; add 20 mL of ethanol-water mixed solution (volume ratio 1:1), perform ultrasonic treatment for 15 minutes (power 250 W, frequency 40 kHz), after cooling to room temperature, make up the volume to the scale with ethanol-water mixed solution, and shake well; take 10 mL of the solution, centrifuge at 3000 r / min for 5 minutes, and take the supernatant as the test solution.

[0045] In addition, the Raman spectroscopy analysis and detection are respectively performed on the blank solution and the reference solution by using the above rapid detection method. Together with the detection data for the sample solution, the SERS characteristic spectra of bismuth subnitrate for each detection test are as Figure 2 shown.

[0046] The preparation method of the blank solution is as follows: Blank solution: Take a 50 mL volumetric flask, add 20 mL of ethanol-water mixed solution (1:1), successively add 0.5 mL of pH 5.5 acetic acid-sodium acetate buffer solution and 0.2 mL of 0.1% NaCl solution, make up the volume with ethanol-water mixed solution, and shake well.

[0047] The preparation method of the reference solution is as follows: Reference solution: Accurately weigh 0.1 g of bismuth subnitrate reference substance (accurate to 0.0001 g), dissolve it with dilute hydrochloric acid (0.1 mol / L) and make up the volume to 100 mL to prepare a 1.0 mg / mL stock solution, and then serially dilute it to a series of concentration solutions of 0.1 - 1.0 mg / mL.

[0048] The Figure 2 shown test results indicate that 1) Blank control (dotted line): There are no obvious characteristic peaks and the baseline is stable; 2) Sample solution (lower solid line): There are obvious characteristic peaks at 1380 cm -1 and 1050 cm -1 ; 3) Reference solution (upper solid line): The positions of the characteristic peaks are the same as those of the sample solution, but the intensity is higher.

[0049] Conclusion: The characteristic peak at 1380 cm -1 corresponds to the vibration of the Bi-O bond and is the characteristic Raman peak of bismuth subnitrate, which proves the specificity and reliability of the test method of the present invention.

[0050] Methodology verification

[0051] I. Detection items

[0052] Determination of the content of bismuth subnitrate in Chenxianglubailu tablets

[0053] II. Verification basis

[0054] General Chapters of the Fourth Volume of Chinese Pharmacopoeia 2025, Guiding Principles for Verification of Pharmaceutical Analysis Methods

[0055] III. Verification Purpose

[0056] To confirm that the linearity, precision, recovery rate, stability, limit of detection (LOD), limit of quantitation (LOQ) and durability of this detection method meet the detection requirements.

[0057] IV. Verification of Linear Relationship

[0058] 4.1 Experimental Design

[0059] Concentration range of reference substance: 0.1 mg / mL - 1.0 mg / mL (covering the actual sample concentration range).

[0060] Drawing of standard curve: Each concentration is determined in parallel 2 times, and the average peak intensity is taken.

[0061] 4.2 Experimental Data

[0062]

[0063] 4.3 Result Analysis

[0064] [[ID=3l]]Regression equation: Y = 1256X + 32.7 (based on patent data, the measured data should be consistent with the standard curve).

[0065] Correlation coefficient (r): 0.9992 (indicating a very significant linear relationship, meeting the requirement of r ≥ 0.999).

[0066] Conclusion: In the range of 0.1 mg / mL - 1.0 mg / mL, there is a good linear relationship between the bismuth subnitrate concentration and the Raman peak intensity.

[0067] V. Precision Verification

[0068] 5.1 Experimental Design

[0069] Sample: The test solution of the same batch of Chenxianglubailu tablets (batch number A, the known bismuth subnitrate content is 98.7% of the labeled amount).

[0070] Number of determinations: Inject the sample repeatedly 6 times, and record the peak intensity at 1380 cm -1 -1.

[0071] 5.2 Experimental Data

[0072]

[0073] 5.3 Result Analysis

[0074] RSD = 1.8% (< 2%), meeting the requirement of RSD ≤ 2% for precision in Chinese Pharmacopoeia.

[0075] Conclusion: The precision of the instrument is good and the repeatability of the method is reliable.

[0076] VI. Recovery Verification (Spiked Recovery Experiment)

[0077] 6.1 Experimental Design

[0078] Sample: Powder of Chenxianglubailu Tablets with known content (Batch No. A, measured content is 0.85 mg / mL, n = 3).

[0079] Spiking Levels: Low (80%), Medium (100%), High (120%), and each level is determined in parallel 3 times.

[0080] 6.2 Experimental Data

[0081]

[0082] 6.3 Result Analysis

[0083] Recovery Range: 97.5% - 103.3%, Average Recovery is 98.5% - 102.3% (meeting the requirement in Pharmacopoeia that the recovery should be between 95% and 105%).

[0084] RSD = 1.2% (< 2%), indicating high method accuracy and small systematic error.

[0085] Conclusion: This method is applicable to the quantitative analysis of bismuth subnitrate content and the results are reliable.

[0086] VII. Stability Verification

[0087] 7.1 Experimental Design

[0088] Sample: The same test solution (Batch No. B).

[0089] Determination Time Points: 0 hour, 2 hours, 4 hours, 8 hours, 12 hours, 24 hours, and record the peak intensity.

[0090] 7.2 Experimental Data

[0091]

[0092] 7.3 Result Analysis

[0093] RSD = 2.3% (< 3%), indicating good stability of the test solution within 24 hours.

[0094] Conclusion: The sample solution can be tested within 24 hours after preparation without re - preparation.

[0095] 8. Limit of Detection (LOD) and Limit of Quantitation (LOQ)

[0096] 8.1 Experimental Design

[0097] Method: Calculated based on the baseline noise (standard deviation, SD) of the blank solution.

[0098] LOD = 3SD (signal-to-noise ratio S / N = 3)

[0099] LOQ = 10SD (signal-to-noise ratio S / N = 10)

[0100] 8.2 Experimental Data

[0101] Baseline noise (SD) of the blank solution: 0.017 μg / mL (obtained by measuring the baseline fluctuations of the blank solution 10 times).

[0102] Calculation results:

[0103] LOD = 3 × 0.017 = 0.051 μg / mL (≈0.05 μg / mL, consistent with the description of the method of the present invention).

[0104] LOQ = 10 × 0.017 = 0.17 μg / mL.

[0105] 8.3 Conclusion

[0106] The limit of detection reaches 0.05 μg / mL, which is better than the traditional titration method (limit of detection is about 0.5 μg / mL), meeting the requirements of trace detection.

[0107] 9. Durability Verification

[0108] 9.1 Experimental Design

[0109] Investigated factors:

[0110] Excitation light power: 150 mW, 200 mW, 250 mW (±50 mW).

[0111] Integration time: 5 s, 10 s, 15 s (±5 s).

[0112] Buffer pH: 5.0, 5.5, 6.0 (±0.5).

[0113] Sample: Reference solution (0.5 mg / mL), measured 2 times under each condition, and calculate RSD.

[0114] 9.2 Experimental Data

[0115]

[0116] 9.3 Result Analysis

[0117] The RSDs were all < 3%, indicating that when each factor varied within a certain range, the impact on the test results was small.

[0118] Conclusion: The method has good durability and is applicable to the tests under different instrument parameters and operating conditions.

[0119] X. Interference Experiment of Excipients

[0120] 10.1 Experimental Design

[0121] Sample: Prepare a blank sample (containing excipients such as licorice and tangerine peel) without bismuth subnitrate according to the prescription ratio of Chenxianglubailu tablets, and process it according to the preparation method of the test solution.

[0122] Detection: Collect the Raman spectrum of the blank sample and observe whether there is a characteristic peak at 1380 cm -1 .

[0123] 10.2 Experimental Results

[0124] Spectrum of the blank sample: There was no obvious peak at 1380 cm -1 , the baseline was stable, and it was consistent with the Figure 2 blank control in

[0125] Conclusion: The excipients have no interference on the characteristic peak of bismuth subnitrate, and the method has strong specificity.

[0126] XI. Verification Conclusion

[0127] This detection method has passed a comprehensive verification, and all indicators meet the requirements of the Chinese Pharmacopoeia and drug analysis methods. The specific conclusions are as follows: Linearity: Good linearity in the range of 0.1 mg / mL - 1.0 mg / mL (r = 0.9992). Precision: RSD = 1.8%, and the instrument repeatability is reliable. Recovery rate: 98.5% - 102.3%, RSD = 1.2%, with high accuracy. Stability: The test solution is stable within 24 hours (RSD = 2.3%). Sensitivity: The detection limit reaches 0.05 μg / mL, which is better than the traditional method. Durability: The fluctuations of key parameters have little impact on the results (RSD < 3%). Specificity: The excipients have no interference, and the characteristic peak is unique.

[0128] The specific embodiments of the present invention have been described in detail above, but they are only examples, and the present invention is not limited to the specific embodiments described above. For those skilled in the art, any equivalent modifications and substitutions to the present invention are also within the scope of the present invention. Therefore, all equivalent transformations and modifications made without departing from the spirit and scope of the present invention should be covered within the scope of the present invention.

Claims

1. A rapid detection method for the main drugs of Chenxianglubailu tablets based on surface-enhanced Raman spectroscopy, characterized in that, It includes the following steps: (1) Provide a clean glass centrifuge tube with a hemispherical bottom for standby; (2) Prepare a gold nanoparticle sol with SERS activity for standby; (3) Fix the gold nanoparticle sol to the bottom of the glass centrifuge tube by chemical bonding to form a SERS active substrate layer; (4) Pour the sample solution containing bismuth subnitrate molecules into the glass centrifuge tube, and then perform detection by Raman spectroscopy analysis.

2. The rapid detection method for the main drugs of Chenxianglu Bailu tablets according to claim 1, wherein, In step (1), the glass centrifuge tube uses a centrifuge tube with a hemispherical bottom, and the bottom thickness is 1-3 mm.

3. The rapid detection method for the main drugs of Chenxianglu Bailu tablets according to claim 1, characterized in that, In step (1), the top of the glass centrifuge tube is threaded with a detachable rotating cap, and a sealing gasket is provided on the inner top of the rotating cap.

4. The rapid detection method for the main drugs of Chenxianglubailu tablets according to claim 1, characterized in that, In step (2), the gold nanoparticle sol is one of gold or silver or copper nanospheres, gold or silver or copper octahedrons, gold or silver or copper nanorods, and gold or silver or copper tetradecahedrons.

5. The rapid detection method for the main drugs of Chenxianglu Bailu tablets according to claim 1, characterized in that, In step (2), the preparation method of the gold nanoparticle sol is as follows: Heat 100 mL of ultrapure water to boiling, quickly add 1 mL of 1% chloroauric acid (HAuCl4) solution, stir evenly, then quickly add 10 mL of 1% sodium citrate solution, continue to boil and stir until the solution color changes from orange-yellow to wine-red, and cool to room temperature to obtain a gold nanoparticle sol with a particle size of 60-80 nm.

6. The rapid detection method for the main drugs of Chenxianglu Bailu tablets according to claim 1, characterized in that, In step (3), first graft an amino group on the inner surface of the bottom of the glass centrifuge tube through a silanization reaction, and then firmly attach the gold nanoparticles by electrostatic adsorption to form a uniform SERS active layer.

7. The rapid detection method for the main medicine of Chenxianglubailu tablets according to claim 1, characterized in that, In step (3), by controlling the concentration and placement time of the gold nanoparticle sol, a uniform SERS active substrate layer with a thickness of about 50-100 nm is formed.

8. The rapid detection method for the main drugs of Chenxianglu Bailu tablets according to claim 1, characterized in that, In step (4), the preparation method of the sample solution is as follows: Take 10 tablets of Chenxianglubailu tablets, grind them finely, accurately weigh 0.1-0.2 g, and place them in a 50 mL volumetric flask; add 20 mL of ethanol-water mixed solution, ultrasonically treat for 15 minutes, cool to room temperature, and then make up the volume to the scale with ethanol-water mixed solution and shake well; take 10 mL of the solution, centrifuge at 3000 r / min for 5 minutes, and take the supernatant as the test solution.

9. The rapid detection method for the main drugs of Chenxianglu Bailu tablets according to claim 1, characterized in that In step (4), the excitation wavelength of the Raman spectrum is 532 - 785 nm, the laser power is 1 - 10 mW, the integration time is 0.5 - 5 s, and the spectral range is 200 - 2000 cm -1 .

10. A mixed reaction device prepared by steps (1)-(3) in the rapid detection method according to any one of claims 1 to 9.