A nitrofurantoin and doxorubicin TDM electrochemical sensor and its preparation method and use

Abstract

The present invention discloses an electrochemical sensor for therapeutic drug concentration monitoring (TDM) of nitrofurantoin and doxorubicin, as well as a preparation method and use thereof. The sensor comprises a base electrode and a composite material modified on the electrode surface. The composite material has a nitrogen-doped graded porous carbon substrate and in-situ gold nanoflowers generated on the surface. The method comprises the following steps: preparing a CuNC material; uniformly coating the CuNC on the electrode surface; surface electroreduction of the gold nanoflowers; and using the electrochemical sensor to detect nitrofurantoin and doxorubicin. The present invention has a low detection limit and high sensitivity and has potential for medical and practical applications. The present invention is simple and easy to prepare and detect.

Description

Technical Field

[0001] The present invention relates to the technical field of nitrofurantoin and doxorubicin TDM detection, and in particular to a nitrofurantoin and doxorubicin TDM electrochemical sensor, a preparation method and application thereof. Background Art

[0002] Nitrofurantoin, a broad-spectrum antibiotic belonging to the nitrofuran family, is particularly effective against bacteria such as Salmonella enterica and Escherichia coli and is commonly used to treat a variety of bacterial infections in animals and humans, including tuberculosis, malaria, and urinary tract infections. Overdose of nitrofurantoin can lead to various disorders, including methemoglobinemia, hepatitis granulomas, pulmonary toxicity, autoimmune hepatitis, chronic active hepatitis, arthritis, and nephrotoxicity. Similarly, doxorubicin, an important anthraquinone antibiotic, is commonly used to treat various cancer types, including Hodgkin's and non-Hodgkin's lymphomas, soft tissue tumors, malignant melanoma, and bronchogenic carcinoma. While doxorubicin is an effective anticancer drug that kills tumor cells, it also has significant drawbacks, including dose-dependent and cumulative cardiotoxicity, liver damage, bone marrow suppression, and allergic reactions, which limit its use in medical applications. Therefore, the development of highly sensitive, convenient, and reliable TDM assays for nitrofurantoin and doxorubicin is highly desirable.

[0003] A variety of analytical methods have been applied to the quantification of nitrofurantoin and doxorubicin, including liquid chromatography-mass spectrometry, high-performance liquid chromatography, surface-enhanced Raman scattering, immunosensors, and molecular imprinting techniques. However, these methods generally require complex sample pretreatment, are difficult and time-consuming to perform, require expensive and bulky instrumentation, and exhibit poor sensitivity and selectivity. Compared to these analytical methods, electrochemical sensors are considered a promising alternative due to their high selectivity, low cost, high sensitivity, portability, and suitability for on-site analysis.

[0004] Copper-based MOFs and their derived carbon nanocomposites have attracted widespread attention in the field of electrochemistry due to their excellent electrocatalytic properties. In this patent, MOFs are combined with polyvinylpyrrolidone via a one-pot solvothermal synthesis method, followed by pyrolysis to produce CuNCs. Gold nanoflowers are then generated in situ on the surface of a modified electrode drop-coated with the materials using electrodeposition. The loading of gold nanoflowers and Cu / Cu2O nanoparticles on the CuNC surface significantly improves conductivity and provides a large number of effective active sites. Furthermore, nitrogen doping not only provides more defects but also modifies the electronic properties of the material, thereby increasing its hydrophilicity and facilitating its dispersibility in water. The gold nanoflowers on the CuNC surface and the material's multimodal pore size distribution improve charge transfer between the active sites and target molecules, enhancing their preconcentration effect and achieving electrochemical signal amplification. Finally, an electrochemical sensor based on the gold nanoflowers on the CuNC surface was successfully used for the detection of nitrofurantoin and doxorubicin TDM with a lower detection limit. Summary of the Invention

[0005] The purpose of the present invention is to provide a nitrofurantoin and doxorubicin TDM electrochemical sensor, a preparation method and an application thereof, so as to solve the problem of complex TDM detection of nitrofurantoin and doxorubicin.

[0006] To achieve the above object, the technical solution of the present invention is as follows:

[0007] A nitrofurantoin and doxorubicin TDM electrochemical sensor comprises a base electrode, a CuNC layer is coated on the surface of the base electrode, and a gold nanoflower layer is electro-reduced outside the CuNC layer.

[0008] A method for preparing a nitrofurantoin and doxorubicin TDM electrochemical sensor, the method comprising the following steps:

[0009] Step 1: Evenly apply the CuNC aqueous suspension on the surface of the base electrode and dry it to obtain a modified electrode; wherein the concentration of the CuNC aqueous suspension is 3-5 mg / mL, and the coating amount of the CuNC aqueous suspension is 0.022-0.067 mL / cm 2 .

[0010] Step 2: placing the modified electrode in a tetrachloroauric acid solution for electroreduction so that the surface of the modified electrode is covered with a gold nanoflower layer, thereby obtaining a nitrofurantoin and doxorubicin TDM electrochemical sensor.

[0011] As a further improvement, the base electrode is a 3 mm diameter glassy carbon electrode.

[0012] As a further improvement, the tetrachloroauric acid solution is a 2-4 mg / mL tetrachloroauric acid aqueous solution.

[0013] As a further improvement, the conditions for the electroreduction are: a reduction voltage of -0.2 to -0.4 volts and a time of 200 to 400 seconds.

[0014] With further improvement, the preparation method of CuNC is as follows:

[0015] 1.1) Weigh 850-900 parts by mass of copper nitrate trihydrate, 250-350 parts by mass of PVP, and 400-450 parts by mass of trimesic acid;

[0016] 1.2) Dissolve copper nitrate trihydrate and PVP in solvent 1 to obtain mixture A;

[0017] Dissolving trimesic acid in solvent 1 to obtain mixture B;

[0018] 1.3) Mix mixtures A and B evenly and transfer them to an autoclave. Control the temperature at 80-120°C and react for 20-25 hours to obtain MOF.

[0019] 1.4) Calcine the MOF at 800°C for 2 hours under a nitrogen atmosphere. After cooling, the product is collected and ground to obtain CuNC.

[0020] As a further improvement, the solvent 1 is a DMF solution, and the water content in the DMF solution is 5-20%.

[0021] A use of the above-mentioned nitrofurantoin and doxorubicin TDM electrochemical sensor is characterized in that the nitrofurantoin and doxorubicin TDM electrochemical sensor is used to detect the concentration of nitrofurantoin or doxorubicin in a solution.

[0022] A further improvement is that when detecting the concentration of nitrofurantoin or doxorubicin in a solution, the pH of the solution is 5-9, and the incubation time of the nitrofurantoin and doxorubicin TDM electrochemical sensors in the aqueous solution is 20-30 minutes; the solution is one of PBS buffer solution, Hac-NaAc buffer solution, HCl buffer solution, aqueous solution or blood.

[0023] In a further improvement, the solution is a PBS buffer solution.

[0024] The advantages of the present invention are as follows:

[0025] 1. In the present invention, gold nanoflowers and CuNC are used to construct the sensor sensing interface. By making standard samples of different concentrations of nitrofurantoin and doxorubicin, the standard samples are co-incubated with the nitrofurantoin and doxorubicin TDM electrochemical sensors to obtain a standard curve with the nitrofurantoin and doxorubicin concentrations as the horizontal axis and the electrochemical signal intensity as the vertical axis, thereby realizing the quantitative detection of the concentrations of nitrofurantoin and doxorubicin; not only has strong catalytic and conductive capabilities, but when used, the sample can be directly incubated with the nitrofurantoin and doxorubicin TDM sensor to obtain the test results. Compared with the detection methods in the prior art, the sensor of the present invention can be used directly without the steps of grinding, preparing a suspension, etc., and is simple and easy to prepare and detect.

[0026] 2. The sensor of the present invention has a detection range of 8*10 -9 -3.5*10 -7 M, the minimum detection limit is 1.405 nM (equivalent to 0.335 ng / mL); the detection range of the sensor for doxorubicin is 10 -8 -1.5*10 -6 M, the minimum detection limit is 1.278 nM (equivalent to 0.729 ng / mL); it can be seen that the sensor prepared by the present invention has an ultra-low detection limit; it has high sensitivity and a low detection limit.

[0027] 3. The nitrofurantoin and doxorubicin TDM electrochemical sensor provided by the present invention has cyclic voltammetry curves and Nyquist curves characterized as follows: Figure 2 As shown in the figure, it is proved that the TDM electrochemical sensor of nitrofurantoin and doxorubicin has strong electrochemical detection performance. The CuNC loaded on gold nanoflowers catalyzes the reaction between nitrofurantoin and doxorubicin, and then electron transfer occurs to generate sensitive current signals, which has high sensitivity for TDM detection of nitrofurantoin and doxorubicin.

[0028] 4. The preparation method of the electrochemical detection nanoprobe of the present invention is simple and easy, with low cost. In addition, the sensor membrane material is a MOF-based derivative material and can be preserved for a long time. Therefore, the sensor of the present invention has the possibility of large-scale production and has the potential for medical and practical applications. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 Schematic diagram of the preparation process of the electrochemical TDM electrochemical sensor for nitrofurantoin and doxorubicin of the present invention, and its use for detecting nitrofurantoin and doxorubicin;

[0030] Figure 2 The scanning electron microscope image and elemental mapping image of CuNC loaded with gold nanoflowers of the present invention;

[0031] Figure 3is the X-ray diffraction pattern of CuNC of the present invention;

[0032] Figure 4 is the X-ray photon energy diagram of CuNC of the present invention;

[0033] Figure 5 Specific surface area and pore size analysis diagram of CuNC of the present invention;

[0034] Figure 6 The cyclic voltammetry curve and Nyquist impedance diagram of the TDM electrochemical sensor of nitrofurantoin and doxorubicin of the present invention are shown in FIG. a a is the cyclic voltammetry curve, b is the Nyquist impedance diagram;

[0035] Figure 7 The cyclic voltammetry curves of the nitrofurantoin and doxorubicin TDM electrochemical sensor of the present invention in a PBS solution containing nitrofurantoin and doxorubicin are shown; two obvious reduction signals appear in the bare glassy carbon electrode group, namely the reduction peaks of nitrofurantoin and doxorubicin ( Figure 7 (a), while with CuNC ( Figure 7 b) and gold nanoflowers ( Figure 7 Middle c) The reduction signals of nitrofurantoin and doxorubicin on the modified glassy carbon electrode gradually increased. When the gold nanoflowers were electro-reduced on the CuNC surface, the reduction signal response of the sensor to nitrofurantoin and doxorubicin reached the highest level.

[0036] Figure 8 Response graphs of the TDM electrochemical sensor for nitrofurantoin and doxorubicin according to the present invention with respect to incubation time, pH, CuNC volume, electroreduction time, electroreduction voltage, and buffer solution;

[0037] Figure 9 Response diagrams of nitrofurantoin and doxorubicin at different scan rates of the TDM electrochemical sensor for nitrofurantoin and doxorubicin of the present invention;

[0038] Figure 10 The electric signal of the nitrofurantoin and doxorubicin TDM electrochemical sensor of the present invention is as follows: -9 -3.5*10 -7 M) and doxorubicin (10 -8 -1.5*10 -6 M) Trend diagram of the change of signal intensity when adding respectively;

[0039] Figure 11 The electric signal of the TDM electrochemical sensor of nitrofurantoin and doxorubicin according to the present invention changes with the electric signal of nitrofurantoin (10 -8 -3*10 -7 M) and doxorubicin (5*10 -8 -1.5*10 -6M) Trend graph of signal intensity changes when adding simultaneously;

[0040] Figure 12 The anti-interference ability test graph and repeatability test graph of the nitrofurantoin and doxorubicin TDM electrochemical sensors after adding different interfering substances in the present invention; DETAILED DESCRIPTION

[0041] To facilitate understanding of the present invention, the present invention will be described more fully below with reference to the accompanying drawings. Preferred embodiments of the present invention are shown in the drawings. However, the present invention may be embodied in many different forms and is not limited to the embodiments described herein. Rather, these embodiments are provided to provide a more thorough and comprehensive disclosure of the present invention.

[0042] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art in the art of the present invention. The terms used in the specification are only for describing specific implementation purposes and are not intended to limit the present invention. Example

[0043] A nitrofurantoin and doxorubicin TDM electrochemical sensor comprises a base electrode, CuNC, and electroreduced gold nanoflowers. The preparation method comprises the following steps:

[0044] Step 1: preparing MOF by hydrothermal synthesis;

[0045] Step 2: calcining the MOF to obtain CuNC;

[0046] Step 3: evenly coating CuNC on the surface of the glassy carbon electrode;

[0047] Step 4: electroreducing the gold nanoflowers in a tetrachloroauric acid solution using the modified electrode obtained in step 3; obtaining a TDM electrochemical sensor for nitrofurantoin and doxorubicin.

[0048] In this embodiment, step one specifically includes the following steps:

[0049] 875 mg of copper nitrate trihydrate and 300 mg of PVP were dissolved in 20 mL of DMF solution and stirred for 10 minutes to obtain mixture A;

[0050] Trimesic acid was also dissolved in 10 mL of DMF solution and stirred for five minutes to obtain mixture B;

[0051] Mixtures A and B were mixed evenly, transferred to a polytetrafluoroethylene autoclave, the temperature was controlled at 80° C., and reacted for 24 hours.

[0052] After the reaction is cooled, the product is collected, transferred to a centrifuge tube, vacuum-dried, and then weighed to obtain MOF.

[0053] In this embodiment, step 2 specifically includes the following steps:

[0054] 1000 mg of MOF was placed in a porcelain boat, transferred to a tube furnace, and calcined at 800 °C for 2 h under a nitrogen atmosphere;

[0055] After the reaction was cooled, the product was collected and ground using an agate mortar for 5 minutes to obtain CuNC.

[0056] In this embodiment, in step 3, the concentration of the CuNC aqueous suspension is 3 mg / mL.

[0057] In this embodiment, step 4 specifically includes the following steps:

[0058] Install the modified electrode prepared in step 3 into the three-electrode system;

[0059] The electrode was immersed in a 3 mg / mL aqueous solution of tetrachloroauric acid;

[0060] Using chronoamperometry at a voltage of -0.4 V and a time of 400 s, gold nanoflowers were electroreduced to obtain TDM electrochemical sensors of nitrofurantoin and doxorubicin.

[0061] The performance of the sensor prepared in this example was tested, and the results were as follows:

[0062] The preparation and detection of the nitrofurantoin and doxorubicin TDM electrochemical sensor Figure 1 As shown, the nitrofurantoin and doxorubicin TDM electrochemical sensor includes a base electrode as well as the CuNC and electroreduced gold nanoflowers.

[0063] like Figure 2 As shown in the ab scanning electron microscopy images, CuNC is evenly distributed on the electrode surface. Figure 2 From the ce, we can see that the surface-reduced gold nanoflowers were successfully prepared and evenly distributed;

[0064] like Figure 3 As shown, X-ray photoelectron spectroscopy shows the presence of corresponding copper and nitrogen elements in the synthesized CuNC.

[0065] like Figure 4 As shown, the prepared CuNC has a microporous-mesoporous-macroporous structure and a high specific surface area;

[0066] like Figure 5 As shown in Figure 3, the X-ray diffraction peaks of CuNC are consistent with those of the standard card of Cu and the standard card of Cu2O, proving the successful synthesis of CuNC.

[0067] like Figure 6 As shown, Figure 6Figure a is a cyclic voltammetry curve commonly used in electrochemical performance characterization. By comparing the strength of the redox signal peaks of different modified electrodes in potassium ferrocyanide solution with the same concentration, the performance of the electrochemical sensor can be preliminarily judged. Figure 6 In the figure b, EIS impedance spectrum is usually used to illustrate the surface impedance of electrochemical sensors. The impedance strength can be intuitively explained by comparing the radius of the arc segments in the impedance diagram. It can be simply understood that the larger the radius of the arc segment, the greater the material impedance. Figure 6 As shown in Figure b, the nitrofurantoin and doxorubicin TDM electrochemical sensor has strong electrical conductivity and good electrochemical performance; the nitrofurantoin and doxorubicin TDM electrochemical sensor prepared by the present invention can be used for sensitive detection of nitrofurantoin and doxorubicin.

[0068] like Figure 7 As shown, by comparing the cyclic voltammetry curves of different modified electrodes in the same PBS solution of nitrofurantoin and doxorubicin, the nitrofurantoin and doxorubicin TDM electrochemical sensor prepared by the present invention has good electrocatalytic activity for nitrofurantoin and doxorubicin.

[0069] like Figure 8 As shown in Figure (a), the effects of incubation times of 1, 5, 10, 15, 20, 25, and 30 minutes on the electrochemical sensor signal intensity were studied. As the incubation time increased to 20 minutes, the electrochemical signal intensity reached a peak. This result indicates that the TDM sensor for nitrofurantoin and doxorubicin exhibited improved sensitivity for the detection of nitrofurantoin and doxorubicin when the incubation time was 20 minutes.

[0070] like Figure 8 As shown in Figure (b), the effects of pH values ​​of 5, 6, 7, 8, and 9 on the electrochemical sensor signal intensity were studied. When the pH was less than 7, the detection sensitivity of the nitrofurantoin and doxorubicin TDM electrochemical sensor gradually decreased with decreasing pH. Conversely, when the pH was greater than 7, the detection sensitivity of the nitrofurantoin and doxorubicin TDM electrochemical sensor gradually decreased with increasing pH. These results indicate that the nitrofurantoin and doxorubicin TDM electrochemical sensor has better sensitivity for the detection of nitrofurantoin and doxorubicin at pH 7.

[0071] like Figure 8As shown in Figure (c), the effect of CuNC coating volume on the signal intensity of the TDM electrochemical sensor for nitrofurantoin and doxorubicin was investigated. When the coating volume was less than 4 μL, the detection sensitivity of the TDM electrochemical sensor for nitrofurantoin and doxorubicin decreased with decreasing volume. Conversely, when the coating volume was greater than 4 μL, the detection sensitivity of the TDM electrochemical sensor for nitrofurantoin and doxorubicin decreased with increasing volume. This result indicates that the TDM electrochemical sensor for nitrofurantoin and doxorubicin exhibited improved sensitivity when 4 μL of CuNC was applied to the surface.

[0072] like Figure 8 As shown in Figure d, the effect of the electroreduction time of gold nanoflowers on the detection sensitivity of nitrofurantoin and doxorubicin TDM electrochemical sensors was studied. When the electroreduction time was 400 seconds, the detection sensitivity of the nitrofurantoin and doxorubicin TDM electrochemical sensors reached the highest.

[0073] like Figure 8 As shown in Figure e, the relationship between the detection sensitivity of the TDM electrochemical sensor for nitrofurantoin and doxorubicin and the reduction voltage of the gold nanoflower was studied. When the reduction voltage was -0.4 volts, the TDM electrochemical sensor for nitrofurantoin and doxorubicin had higher detection sensitivity.

[0074] like Figure 8 As shown in Figure f, the effects of Hac-NaAc, PBS, and HCl buffer on the response intensity of the TDM electrochemical sensor for nitrofurantoin and doxorubicin were studied. The results showed that the TDM electrochemical sensor for nitrofurantoin and doxorubicin in PBS solution had higher sensitivity to nitrofurantoin and doxorubicin.

[0075] like Figure 9 As shown, the electrochemical responses of nitrofurantoin and doxorubicin on the surface of the nitrofurantoin and doxorubicin TDM electrochemical sensor changed with the change of scan rate. Figure 9 Figure b shows that the reduction current of nitrofurantoin is linearly correlated with the logarithm of the scan rate, while the reduction current of doxorubicin is linearly correlated with the scan rate. This indicates that nitrofurantoin is diffusion-controlled on the electrode surface, while doxorubicin is adsorption-controlled.

[0076] The quantitative detection of nitrofurantoin and doxorubicin using the nitrofurantoin and doxorubicin TDM electrochemical sensor includes the following steps:

[0077] Weigh nitrofurantoin powder and dilute it with DMF:water (1:1) to prepare a 1 mM stock solution. At the same time, weigh doxorubicin powder and dilute it with water to prepare a 1 mM stock solution. Add PBS to the nitrofurantoin stock solution and the doxorubicin stock solution at different ratios to dilute them. The standard solutions of nitrofurantoin and doxorubicin coexisting at different concentrations were obtained and used as test samples to incubate with the nitrofurantoin and doxorubicin TDM electrochemical sensor for 20 min. Repeat 3 times for each concentration and record the electrochemical signal intensity value. Figure 10 As shown in Figure 2, the electrochemical signal intensity increases with the increase of nitrofurantoin and doxorubicin concentrations. In addition, a standard curve was drawn with nitrofurantoin concentration as the horizontal axis and electrochemical signal intensity as the vertical axis. Figure 11 b, has a good linear relationship R 2 =0.9995, LOD = 1.405 nM; with doxorubicin concentration as the horizontal axis and electrochemical affinity as the vertical axis, a standard curve was drawn 11d, which showed a good linear relationship R 2 =1.278, LOD=1.278 nM. Conclusion: The linear range of nitrofurantoin detection is 8*10 -9 -3.5*10 -7 M, LOD was 1.405 nM; the linear range of detection for doxorubicin was 10 -8 -1.5*10 -6 The detection limit of the sensor system was 1.278 nM and the detection limit was 1.278 nM. The sensor system had a wide linear range and an extremely low detection limit, and had good reproducibility in repeated experiments.

[0078] A quantitative analysis was conducted on the simultaneous changes in the concentrations of nitrofurantoin and doxorubicin. Figure 12 When the concentration of doxorubicin was five times that of nitrofurantoin, the electrochemical signals of each increased simultaneously with the increase of the concentration of nitrofurantoin and doxorubicin, showing an excellent linear relationship: I = 0.06022 C + 3.3339 (R 2 =0.9982); I of doxorubicin = 0.5828 C + 4.4270 (R 2 =0.9988). These results indicate that the TDM electrochemical sensor for nitrofurantoin and doxorubicin can be used for sensitive detection of nitrofurantoin and doxorubicin.

[0079] Anti-interference experiments, repeatability and stability experiments were carried out on the TDM electrochemical sensors for nitrofurantoin and doxorubicin:

[0080] like Figure 12 a. After adding protein-precipitated serum to the standard sample, the electrochemical signal does not attenuate, indicating that the prepared electrochemical sensor has excellent anti-interference performance; the repeatability and stability test results of the sensor are shown in Figure 2. Figure 12(b-c), Five groups of different sensors were tested five times and showed good repeatability and stability.

[0081] Table 1

[0082]

[0083] Table 1 shows the contents and recoveries of nitrofurantoin and doxorubicin in standard serum samples measured by the nitrofurantoin and doxorubicin TDM electrochemical sensors of the present invention.

[0084] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions and improvements made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. A use of a nitrofurantoin and doxorubicin TDM electrochemical sensor, characterized in that: The nitrofurantoin and doxorubicin TDM electrochemical sensor comprises a base electrode, a CuNC layer is coated on the surface of the base electrode, and a gold nanoflower layer is electro-reduced on the outer surface of the CuNC layer; the nitrofurantoin and doxorubicin TDM electrochemical sensor is used to detect the concentration of nitrofurantoin or doxorubicin in a solution; The preparation method of CuNC is as follows: 1.1) Weigh 850-900 parts by mass of copper nitrate trihydrate, 250-350 parts by mass of PVP, and 400-450 parts by mass of trimesic acid; 1.2) Dissolve copper nitrate trihydrate and PVP in solvent 1 to obtain mixture A; Dissolving trimesic acid in solvent 1 to obtain mixture B; 1.3) Mix mixtures A and B evenly and transfer them to an autoclave. Control the temperature at 80-120°C and react for 20-25 hours to obtain MOF. 1.4) calcining the MOF at 800°C for 2 hours under a nitrogen atmosphere; after cooling, collecting the product and grinding it to obtain CuNC; the solvent 1 is a DMF solution, and the water content of the DMF solution is 5-20%.

2. The use of a nitrofurantoin and doxorubicin TDM electrochemical sensor according to claim 1, characterized in that: The method for preparing the nitrofurantoin and doxorubicin TDM electrochemical sensor comprises the following steps: Step 1: Evenly apply the CuNC aqueous suspension on the surface of the base electrode and dry it to obtain a modified electrode; wherein the concentration of the CuNC aqueous suspension is 3-5 mg / mL, and the coating amount of the CuNC aqueous suspension is 0.022-0.067 mL / cm 2 ; Step 2: placing the modified electrode in a tetrachloroauric acid solution for electroreduction so that the surface of the modified electrode is covered with a gold nanoflower layer, thereby obtaining a nitrofurantoin and doxorubicin TDM electrochemical sensor.

3. The use of a nitrofurantoin and doxorubicin TDM electrochemical sensor according to claim 2, characterized in that: The base electrode is a 3 mm diameter glassy carbon electrode.

4. The use of a nitrofurantoin and doxorubicin TDM electrochemical sensor according to claim 2, characterized in that: The tetrachloroauric acid solution is a 2-4 mg / mL tetrachloroauric acid aqueous solution.

5. The use of a nitrofurantoin and doxorubicin TDM electrochemical sensor according to claim 2, characterized in that: The conditions for the electroreduction are: reduction voltage of -0.2-0.4V, and time of 200-400 seconds.

6. Use of the nitrofurantoin and doxorubicin TDM electrochemical sensor according to claim 1, characterized in that: When detecting the concentration of nitrofurantoin or doxorubicin in a solution, the pH of the solution is 5-9, and the nitrofurantoin and doxorubicin TDM electrochemical sensors are incubated with the solution in the aqueous solution for 20-30 minutes; the solution is one of PBS buffer solution, Hac-NaAc buffer solution, HCl buffer solution, aqueous solution or blood.

7. Use of the nitrofurantoin and doxorubicin TDM electrochemical sensor according to claim 1, characterized in that: The solution is a PBS buffer solution.

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