SERS (Surface Enhanced Raman Scattering) substrate and detection method for blood concentration of epirubicin

Abstract

The invention provides an SERS (Surface Enhanced Raman Scattering) substrate and a detection method for the blood concentration of epirubicin, and belongs to the technical field of detection.The SERS substrate is prepared by the following steps: firstly, respectively preparing 40nm and 20nm gold nanoparticles through a sodium citrate reduction method, and constructing the SERS substrate on a silicon dioxide sheet through ABA sandwich dispensing; an epirubicin blood sample is pretreated through an acetonitrile precipitation method and then dropwise added to the substrate to be dried away from light, and the 1236 cm <-1 > characteristic peak intensity is detected through a 785 nm Raman spectrum. By establishing a quantitative curve of epirubicin concentration and peak intensity in serum, rapid quantitative detection of clinical samples is realized. The method is simple in sample treatment, high in detection sensitivity, good in repeatability, consistent with LC-MS / MS results, and suitable for bedside treatment drug monitoring.

Description

Technical Field

[0001] This invention belongs to the field of detection technology, specifically relating to a SERS substrate for epirubicin blood concentration and a detection method thereon. Background Technology

[0002] Epirubicin (EPI) is an anthracycline antibiotic used to treat tumors. It is an isomer of doxorubicin (doxorubicin) and inhibits DNA and RNA synthesis by directly intercalating between DNA base pairs, interfering with transcription, and preventing mRNA formation. This drug has inhibitory effects on various solid tumors such as leukemia, malignant lymphoma, breast cancer, lung cancer, ovarian cancer, and gastric cancer.

[0003] Epirubicin has a narrow therapeutic window, with an effective peak plasma concentration range typically between 0.1 and 1 μg / mL (approximately 1.72 × 10⁻⁶). -7 ~1.72×10 -6 M). When peak plasma concentrations exceed this range, severe toxic reactions are likely to occur. When plasma concentrations >2 μg / mL (3.45 × 10⁻⁶), severe toxic reactions are more likely to occur. -6 At times (M), the risk of cardiotoxicity in patients is significantly increased. The incidence and severity of epirubicin cardiotoxicity are directly proportional to the cumulative dose in the body. Delayed severe heart failure usually occurs after six months of use or when the total dose exceeds 700-800 mg / m². 2 It happens at any time.

[0004] Epirubicin has complex pharmacokinetic characteristics, exhibiting a three-compartment distribution in vivo. It is primarily excreted via the hepatobiliary system, with 40%–45% of the administered dose excreted in feces and only 7%–23% excreted in urine via the kidneys. This relatively long terminal half-life means that the drug may accumulate in the body, especially in patients requiring multiple cycles of treatment. Therefore, long-term monitoring of blood drug concentrations is crucial for individualized dosing and safety management.

[0005] Epirubicin pharmacokinetics vary significantly among individuals and are affected by multiple factors: hepatic function status (50% dose reduction for moderate hepatic impairment, 75% dose reduction for severe hepatic impairment); renal function status (no dose adjustment required for moderate renal impairment, but dose reduction should be considered for severe renal impairment); age (caused by caution in elderly patients, especially those with impaired cardiac function, and the total cumulative dose should be reduced accordingly); and combination therapy (increased risk of cardiotoxicity when used in combination with other potentially cardiotoxic drugs or in patients who have previously received chest radiotherapy, requiring dose adjustment).

[0006] Given epirubicin's narrow therapeutic window, significant individual pharmacokinetic variability, and potential serious toxicities (especially dose-cumulative cardiomyopathy and myelosuppression), therapeutic drug monitoring (TDM) during treatment is extremely important. Reliable TDM can guide clinicians to adjust the dosing regimen in a timely manner based on the patient's actual blood drug concentration, maximizing efficacy while minimizing toxicity risks, thus achieving personalized and precise treatment. However, current mainstream methods have significant limitations: ① High-performance liquid chromatography (HPLC) requires complex sample pretreatment (such as solid-phase extraction), analysis time can exceed 30 minutes, and the equipment is expensive, making it difficult to meet the needs of clinical point-of-care testing. ② Liquid chromatography-mass spectrometry (LC-MS) has stringent requirements for instrument environment and maintenance, with a single test costing over a thousand yuan. ③ Enzyme-linked immunosorbent assay (ELISA) has low sensitivity and a high risk of false negatives. ④ Although electrochemical sensor technology (such as molecularly imprinted polymers) has been explored in recent years, its practical application still faces many problems, including technical complexity, reliance on large-scale instruments, the need for professional personnel to operate, high cost, and poor stability.

[0007] This invention aims to propose a rapid detection system for epirubicin blood drug concentration. By utilizing the SERS characteristic peak of epirubicin to distinguish and identify epirubicin, a drug gradient concentration quantitative model is established for drug concentration quantification. It features rapid detection, low cost, high sensitivity, and high specificity. Summary of the Invention

[0008] This invention addresses the limitations of existing detection methods and shortcomings in previous research by proposing a SERS substrate and detection method for epirubicin blood concentration. The method utilizes a constructed ABA-sandwich SERS substrate to detect trace amounts of epirubicin in patient blood. Specifically, after simple blood sample processing, the sample is dropped onto the SERS substrate for detection, yielding quantitative results. This detection method is convenient, rapid, low-cost, highly sensitive, and highly specific. Physicians can perform the test at the bedside without relying on the involvement of physicians from pathology, laboratory, or other related departments.

[0009] This invention preprocesses blood samples for testing and uses a SERS substrate for epirubicin detection. This method can obtain epirubicin blood concentration results within minutes.

[0010] To solve the above-mentioned technical problems, the specific technical solution of the present invention is as follows:

[0011] A SERS method for detecting epirubicin blood concentration includes the following steps:

[0012] 1. Blood sample processing:

[0013] (1) Take 1 ml of peripheral blood sample and centrifuge it at 4℃, 3000 r / min for 10 min.

[0014] (2) Take the supernatant obtained from (1) of this section, discard the precipitate, add 0.1 ml of acetonitrile to 0.2 ml of serum sample, mix well and let stand for 1 min. After obvious precipitation, centrifuge at 5000 r / min for a total of 5 min.

[0015] (3) Take the supernatant obtained from (2) of this section, discard the precipitate, add 0.01 ml of acetonitrile again, mix well, let stand for 1 min, centrifuge at 8000 r / min for a total of 5 min;

[0016] (4) Obtain the supernatant from (3) of this section as the test sample and discard the precipitate.

[0017] 2. Constructing high-efficiency SERS substrates using gold nanoparticles of different diameters:

[0018] (1) Using HAuCl4 as a seed and sodium citrate as a reducing agent, two types of gold nanoparticles, A and B, with diameters of 40 nm and 20 nm respectively, were prepared in 1:1 and 1:4 addition environments. The concentrations were 6 × 10⁻⁶ ppm. 8 cells / ml, 2.4×10 9 Two gold nanoparticle-sodium citrate solutions, A and B, were prepared at 4500 r / min for 10 min at room temperature. The liquid in the tube was discarded, and ddH2O was added to the precipitate at 80 times its own volume and mixed well to form a gold nanoparticle suspension.

[0019] (2) Take 5 μL of the above two suspensions, A and B. First, gently drop A onto the silicon dioxide wafer and let it air dry at room temperature. Then, drop B onto the wafer and let it air dry again. Then, drop A onto the wafer and let it air dry again. After the nanoparticles are dried, an ABA sandwich structure high-efficiency SERS substrate is formed on the surface of the silicon wafer.

[0020] 3. Identification of characteristic peaks of the standard product:

[0021] (1) Preparation of epirubicin standard solution: Dissolve 5.80 mg of epirubicin in 10 ml of ultrapure water to prepare a solution of 1×10 -3 M epirubicin standard solution; subsequently serially diluted to 1×10 -5 Up to 1×10 -9 M cyclophosphamide standard solution; process should be protected from light and high temperatures;

[0022] (2) Take 5 μL of the sample to be tested prepared in (1) of this section and drop it onto the constructed SERS substrate and let it dry;

[0023] (3) SERS detection was performed using a portable Raman spectrometer, model RPB-785-1.5-FS. The excitation wavelength of the Raman spectrometer was 785 nm, the detection power was 30 mW, and the integration time was 0.5 s. The spectrum of the sample was obtained, and the characteristic shift of the pararubidium star was 1202 cm⁻¹. -1 1236cm -1 .

[0024] 4. Construction of SERS quantification curve for epirubicin in serum:

[0025] (1) Preparation of serum epirubicin solution: Prepare 1×10 according to section 3(1). -3 M epirubicin standard solution; add serum to prepare 1×10 -4 M's serum drug mixture solution; subsequently serially diluted to 1×10 -5 M to 1×10 -9 M epirubicin serum solution; process should be protected from light and high temperatures;

[0026] (2) The serum epirubicin solutions of different concentrations obtained in step (1) were pretreated according to the above blood sample processing method to obtain 1×10 -5 M to 1×10 -9 M epirubicin serum solution;

[0027] (3) Take 5 μL of the sample to be tested and drop it onto the constructed SERS substrate and let it dry;

[0028] (4) SERS detection was performed using a portable Raman spectrometer, model RPB-785-1.5-FS. The excitation wavelength of the Raman spectrometer was 785 nm, the detection power was 30 mW, and the integration time was 0.5 s. The spectrum of the sample was obtained, and the characteristic shift of the epirubicin was 1207 cm⁻¹. -1 1236cm -1 .

[0029] (5) Plot quantitative curves from the SERS spectra of epirubicin serum solutions of different concentrations.

[0030] 5. SERS detection and data output of epirubicin blood concentration in cancer patients:

[0031] (1) On the second day after epirubicin chemotherapy in cancer patients, peripheral blood samples were taken and blood was processed according to the method in section 1;

[0032] (2) After adding 5 μL of the serum sample to be tested onto the constructed SERS substrate, air dry at room temperature in the dark;

[0033] (3) SERS detection was performed using a portable Raman spectrometer, model RPB-785-1.5-FS. The excitation wavelength of the Raman spectrometer was 785 nm, the detection power was 30 mW, and the integration time was 0.5 s. The spectrum of the sample was obtained and observed at 1207 cm⁻¹. -1 1236cm -1 Spectral peak at the displacement;

[0034] (4) The measured spectral peaks are incorporated into the quantitative curve to obtain the drug concentration of epirubicin.

[0035] Beneficial effects:

[0036] 1. The serum sample processing method of the present invention is simple, portable, low-cost, and effective.

[0037] 2. This invention provides a SERS method for detecting epirubicin blood drug concentration. This method is simple to operate, highly sensitive, and fast, with the time from blood sample collection to result output not exceeding half an hour; in batch testing of multiple samples, the average time per sample is only about 2 minutes, making it widely applicable for rapid and accurate detection of epirubicin blood drug concentration after chemotherapy. Attached Figure Description

[0038] Figure 1 1×10 -7 M concentration table of SERS detection spectra of rubella in different solutions and serum control.

[0039] Figure 2 Serum epirubicin SERS spectral quantitative curve.

[0040] Figure 3 For a concentration of 1×10 -7 M epirubicin serum samples were repeatedly measured (n=20 times), with spectra acquired at 1236 cm⁻¹. -1 The intensity of the Raman characteristic peak at that location.

[0041] Figure 4 Epirubicin SERS detection and concentration prediction in clinical serum samples: raw SERS spectra of serum samples from three patients (P001-P003). Detailed Implementation

[0042] The present invention will now be described in detail with reference to the accompanying drawings and specific embodiments. However, the following embodiments are only for explaining the present invention, and the scope of protection of the present invention should include all the contents of the claims. Moreover, through the description of the following embodiments, those skilled in the art can fully implement all the contents of the claims of the present invention.

[0043] Example 1:

[0044] Patient P001, female, 55 years old, was diagnosed with breast cancer in April 2025 and underwent epirubicin chemotherapy.

[0045] (1) 1 ml of peripheral blood was collected using a coagulation-promoting tube 24 h after the patient received intravenous epirubicin and centrifuged for 10 min at 4°C and 3000 r / min.

[0046] Take 0.2 ml of serum, add 0.1 ml of acetonitrile, mix well and let stand for 1 min. After obvious precipitation, centrifuge at 5000 r / min for 5 min and discard the precipitate. Add 0.01 ml of acetonitrile again, mix well and let stand for 1 min, centrifuge at 8000 r / min for 5 min and discard the precipitate again to obtain the sample to be tested.

[0047] (2) Using HAuCl4 as a seed and sodium citrate as a reducing agent, two types of gold nanoparticles, 40 nm and 20 nm in solution A and solution B, were prepared in 1:1 and 1:4 addition environments, respectively. (Solution A: diameter 40 nm, Solution B: diameter 20 nm) 8 cells / ml, 2.4×10 9 Two gold nanoparticle-sodium citrate solutions, A and B, were prepared at 4500 r / min for 10 min at room temperature. The liquid in the tube was discarded, and ddH2O was added to the precipitate at 80 times its own volume and mixed well to form a gold nanoparticle suspension.

[0048] (3) Take 5 μL of the above two suspensions, A and B. First, gently drop A onto the silicon dioxide wafer and let it air dry at room temperature. Then, drop B onto the wafer and let it air dry again. Then, drop A onto the wafer and let it air dry again. After the nanoparticles are dried, an ABA sandwich structure high-efficiency SERS substrate is formed on the surface of the silicon wafer.

[0049] (4) Take 5 μL of the sample to be tested and drop it onto the substrate to air dry at room temperature in the dark; set the excitation wavelength of the Raman spectrometer to 785 nm, the detection power to 30 mW, and the integration time to 0.5 s to obtain the spectrum of the sample to be tested, and observe it at 1207 cm⁻¹. -1 1236cm -1 Spectral peak at the displacement;

[0050] (5) The measured 1236cm -1 The spectral peak at the displacement was incorporated into the quantitative curve, yielding a serum epirubicin drug concentration of 5.36 × 10⁻⁶. -8 M.

[0051] Example 2:

[0052] Patient P002, female, 49 years old, was diagnosed with breast cancer in April 2025 and underwent epirubicin chemotherapy.

[0053] (1) 24 hours after the patient received an intravenous infusion of epirubicin, 1 ml of peripheral blood was collected using a coagulation-promoting tube and centrifuged for 10 min at 4°C and 3000 r / min. 0.2 ml of serum was taken, 0.1 ml of acetonitrile was added, mixed, and allowed to stand for 1 min. After a clear precipitate appeared, centrifugation was performed at 5000 r / min for a total of 5 min. The precipitate was then discarded. 0.01 ml of acetonitrile was added again, mixed, and allowed to stand for 1 min. The mixture was then centrifuged at 8000 r / min for a total of 5 min. The precipitate was discarded again to obtain the sample to be tested.

[0054] (2) Using HAuCl4 as a seed and sodium citrate as a reducing agent, two types of gold nanoparticles, 40 nm and 20 nm in solution A and solution B, were prepared in 1:1 and 1:4 addition environments, respectively. (Solution A: diameter 40 nm, Solution B: diameter 20 nm) 8 cells / ml, 2.4×10 9 Two gold nanoparticle-sodium citrate solutions, A and B, were prepared at 4500 r / min for 10 min at room temperature. The liquid in the tube was discarded, and ddH2O was added to the precipitate at 80 times its own volume and mixed well to form a gold nanoparticle suspension.

[0055] (3) Take 5 μL of the above two suspensions, A and B. First, gently drop A onto the silicon dioxide wafer and let it air dry at room temperature. Then, drop B onto the wafer and let it air dry again. Then, drop A onto the wafer and let it air dry again. After the nanoparticles are dried, an ABA sandwich structure high-efficiency SERS substrate is formed on the surface of the silicon wafer.

[0056] (4) Take 5 μL of the sample to be tested and drop it onto the substrate to air dry at room temperature in the dark; set the excitation wavelength of the Raman spectrometer to 785 nm, the detection power to 30 mW, and the integration time to 0.5 s to obtain the spectrum of the sample to be tested, and observe it at 1207 cm⁻¹. -1 1236cm -1 Spectral peak at the displacement;

[0057] (5) The measured 1236cm -1 The spectral peak at the displacement was incorporated into the quantitative curve, yielding a serum epirubicin drug concentration of 1.85 × 10⁻⁶. -8 M.

[0058] Example 3:

[0059] Patient P003, female, 52 years old, was diagnosed with breast cancer in May 2025 and underwent epirubicin chemotherapy.

[0060] (1) 24 hours after the patient received an intravenous infusion of epirubicin, 1 ml of peripheral blood was collected using a coagulation-promoting tube and centrifuged for 10 min at 4°C and 3000 r / min. 0.2 ml of serum was taken, 0.1 ml of acetonitrile was added, mixed, and allowed to stand for 1 min. After a clear precipitate appeared, centrifugation was performed at 5000 r / min for a total of 5 min. The precipitate was then discarded. 0.01 ml of acetonitrile was added again, mixed, and allowed to stand for 1 min. The mixture was then centrifuged at 8000 r / min for a total of 5 min. The precipitate was discarded again to obtain the sample to be tested.

[0061] (2) Using HAuCl4 as a seed and sodium citrate as a reducing agent, two types of gold nanoparticles, 40 nm and 20 nm in solution A and solution B, were prepared in 1:1 and 1:4 addition environments, respectively. (Solution A: diameter 40 nm, Solution B: diameter 20 nm) 8 cells / ml, 2.4×10 9 Two gold nanoparticle-sodium citrate solutions, A and B, were prepared at 4500 r / min for 10 min at room temperature. The liquid in the tube was discarded, and ddH2O was added to the precipitate at 80 times its own volume and mixed well to form a gold nanoparticle suspension.

[0062] (3) Take 5 μL of the above two suspensions, A and B. First, gently drop A onto the silicon dioxide wafer and let it air dry at room temperature. Then, drop B onto the wafer and let it air dry again. Then, drop A onto the wafer and let it air dry again. After the nanoparticles are dried, an ABA sandwich structure high-efficiency SERS substrate is formed on the surface of the silicon wafer.

[0063] (4) Take 5 μL of the sample to be tested and drop it onto the substrate to air dry at room temperature in the dark; set the excitation wavelength of the Raman spectrometer to 785 nm, the detection power to 30 mW, and the integration time to 0.5 s to obtain the spectrum of the sample to be tested, and observe it at 1207 cm⁻¹. -1 1236cm -1 Spectral peak at the displacement;

[0064] (5) The measured 1236cm -1 The spectral peak at the shift point was incorporated into the quantitative curve, yielding a serum epirubicin drug concentration of 6.66 × 10⁻⁶. -8 M.

[0065] Analysis of test and experimental results:

[0066] like Figure 1 As shown, Figure 1 1×10 -7 SERS spectra of epirubicin at concentration M in double-distilled water and serum. Epirubicin was detected by SERS in double-distilled water, with a characteristic shift of 1202 cm⁻¹. -1 1236cm -1After processing in serum, SERS was performed, and the characteristic shift was 1207 cm⁻¹. -1 1236cm -1 .

[0067] like Figure 2 As shown, Figure 2 The SERS spectrum of epirubicin in serum was used to quantify the drug. Epirubicin serum solutions of different concentrations were subjected to SERS spectroscopy. The optimal molecular weight of epirubicin at 1236 cm⁻¹ was selected. -1 The characteristic Raman vibration peak at this location was used as the target peak for quantitative analysis. This peak is attributed to the CH, COH, and CO vibrations of the anthracene ring skeleton and exhibits a significant and stable Raman signal. Figure 2 As shown, the intensity of this characteristic peak (y-axis, I) and the concentration of epirubicin in serum (x-axis, lg(c)) are related in the range of 1×10⁻⁶. -9 Up to 1×10 -4 A good linear relationship is observed within the range of M. Through linear fitting, the linear regression equation is obtained as I = 19302 + 1782 × lg(c), and its correlation coefficient (R²) is [missing value]. 2 The linearity is 0.9933, indicating that the quantitative model has high linearity and reliability.

[0068] like Figure 3 As shown, Figure 3 The concentration shown is 1×10 -7 M epirubicin serum samples were repeatedly measured (n=20 times), with spectra acquired at 1236 cm⁻¹. -1 The Raman characteristic peak intensity at the location was measured. The signal intensity obtained from multiple measurements was closely distributed around the average value, with a relative standard deviation (RSD) of 7.65%. This method exhibits good repeatability and high precision in detecting epirubicin blood concentration.

[0069] like Figure 4 As shown, to verify the clinical applicability of this SERS detection method, blood samples were collected from patients who received epirubicin chemotherapy 24 hours after administration and analyzed in a blinded test. Figure 4 As shown, the original SERS spectra of the three patients (P001-P003) were in the range of 600-1600 cm⁻¹. -1 Characteristic signals of Epirubicin were successfully acquired within the entire range. Extraction was performed at 1236 cm⁻¹. -1The Raman characteristic peak intensity was calculated and substituted into the established standard curve equation (I=19302+1782×lg(c)) to successfully predict the trough concentration of epirubicin in the serum of the three patients, as shown in Table 1 below. To confirm the accuracy of the SERS method established in this study, we used liquid chromatography-tandem mass spectrometry (LC-MS / MS), the recognized gold standard, to perform blinded validation analysis on the serum samples of the above three patients (P001, P002, P003). As shown in Table 1 below, the predicted results of the SERS method were compared with the mass spectrometry results, and the two showed a high degree of consistency. This serum epirubicin SERS detection method can rapidly detect results, providing real-time evidence for personalized and precise clinical drug administration.

[0070] Table 1 shows the predicted concentration of epirubicin, the LC-MS / MS verified concentration, and the relative error calculated based on the characteristic peak intensity and the standard curve.

[0071] Table 1

[0072] The above description is merely a specific embodiment of this application, enabling those skilled in the art to understand or implement this application. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of this application. Therefore, this application is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features claimed herein.

Claims

1. A SERS substrate for epirubicin blood concentration, characterized in that, Its preparation process includes the following steps: Preparation of 40nm gold nanoparticles in solution A: Synthesized in a 1:1 addition environment using HauCl4 as seed and sodium citrate as reducing agent; Preparation of 20nm gold nanoparticles in solution B: Synthesized in a 1:4 addition environment using HAuCl4 as seed and sodium citrate as reducing agent. The concentration is 6×10 8 A suspension of particles A at a concentration of 2.4 × 10⁻⁶ / mL and a concentration of 2.4 × 10⁻⁶ / mL. 9 The B particle suspension was centrifuged at 4500 r / min for 10 min, the supernatant was discarded, and the precipitate was resuspended in 80 volumes of ddH2O. 5 μL of solution A was added dropwise to a silica substrate and allowed to dry. Then 5 μL of solution B was added dropwise and allowed to dry. Then 5 μL of solution A was added dropwise and allowed to dry, forming an ABA sandwich structure SERS substrate.

2. The SERS substrate according to claim 1, characterized in that, The diameter of gold nanoparticle A is 40±5nm, and the diameter of gold nanoparticle B is 20±3nm.

3. A SERS method for detecting epirubicin blood concentration, characterized in that, Includes the following steps: Blood sample pretreatment: Take 0.2 mL of serum, add 0.1 mL of acetonitrile, mix well, let stand for 1 min, then centrifuge at 5000 r / min for 5 min; take the supernatant, add 0.01 mL of acetonitrile, mix well, then centrifuge at 8000 r / min for 5 min to obtain the sample to be tested; Using the SERS substrate described in claim 1 or 2, add 5 μL of the sample to be tested and air dry in the dark; Detection was performed using a Raman spectrometer with an excitation wavelength of 785 nm and a power of 30 mW. The integration time was 0.5 s, and a sample size of 1236 cm⁻¹ was collected. -1 Characteristic peak intensity; The concentration of tabularubicin was calculated based on a pre-established quantitative curve.

4. The method according to claim 3, characterized in that, Before pretreatment, the blood samples need to be centrifuged at 4°C and 3000 r / min for 10 min to separate the serum.

5. The method according to claim 3, characterized in that, The quantitative curve is established through the following steps: Prepare 1×10 -4 M to 1×10 -9 Epirubicin serum solutions with M gradient concentrations; The serum solution underwent the same pretreatment. Detection of 1236 cm on SERS substrate -1 Peak intensity was used to establish a linear equation: I = 19302 + 1782 × lg(c).

6. The method according to claim 3, characterized in that, A 1207cm sample was collected simultaneously during the test. -1 Characteristic peaks serve as auxiliary quantitative references.

7. A method for identifying characteristic peaks of a pirouette star, characterized in that, include: Prepare 1×10 -4 M to 1×10 -9 M-type epirubicin aqueous solution; Using the SERS substrate described in claim 1 or 2, a characteristic peak at 1202 cm⁻¹ was obtained at an excitation wavelength of 785 nm. -1 and 1236cm -1 .

8. A reagent kit for detecting epirubicin blood drug concentration, characterized in that, Include: The ABA sandwich structure SERS substrate as described in claim 1 or 2; Acetonitrile sample processing solution; Epirubicin quantitative curve standard card, concentration range 1×10⁻⁶ -9 M to 1×10 -4 M.

9. The reagent kit according to claim 8, characterized in that, The quantitative curve standard card is marked 1236cm. -1 The linear equation relating peak intensity to concentration is I = 19302 + 1782 × lg(c).

10. A portable epirubicin blood drug concentration analyzer, characterized in that, integrated: The SERS substrate loading module as described in claim 1 or 2; 785nm laser source and spectral detector; The quantitative curve algorithm described in claim 5 is incorporated.

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