Electro-polymerization of modified carbon paste sensor for detecting Azithromycin

Electro-polymerization of modified carbon paste sensor for detecting Azithromycin | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Electro-polymerization of modified carbon paste sensor for detecting Azithromycin salma mamdouh, mohammed shehata, amany fekry, magda ameer This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4737822/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted 11 You are reading this latest preprint version Abstract A carbon paste electrode (CPE) was simply modified to detect AM using poly-threonine (PT). Azithromycin (AM) is one of the prescribed drugs in pandemic medication regimen which has a paying attention. The work was characterised using electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). A very sensitive response to the oxidation of 1.0 mM AM in phosphate buffer solution (PBS) over a pH range of 5.0 to 10.0 was observed using a developed poly-threonine carbon paste electrode (PTCPE). In PBS with a pH of 7.4, the impact of different AM concentrations was investigated resulting in a detection limit of 0.32 µM and a quantification limit of 1.07 µM. Finally, the recently used electrode realized acceptable sensitivity and consistency for AM detection in pharmaceutical drugs. Earth and environmental sciences/Environmental sciences Physical sciences/Chemistry L-Threonine COVID-19 Electropolymerization Antiviral Azithromycin Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 1. Introduction The semisynthetic macrolide antibiotic AM (9-Deoxo-9a-aza-9a-methyl-9a-homoerythromycin A) (Supplementary Scheme S1A) is generated by remodeling the naturally occurring antibiotic, erythromycin (Supplementary Scheme S1B) through replacing the carbonyl group at the 9a site of the aglycone ring by a methyl-substituted nitrogen resultant in a 15-membered ring termed as an azalide [ 1 ]. AM exhibits a broad spectrum of antibacterial activity, as a result, it is typically used to treat a wide range of mild-to-moderate bacterial infections. As well as its antibacterial effects, AM has been reported to have antiviral properties in vitro and/or in vivo against a variety of viruses, including Ebola [ 2 ], Zika [ 3 ] and influenza H1N1 virus [ 4 ]. AM also manifests an antiviral activity against SARS-CoV-2 [ 5 – 9 ]. The world health organization (WHO) described COVID-19 as a global pandemic that has produced millions of fatalities globally. AM detection in real samples is important as being one of the prescribed medications alongside paracetamol, zinc and vitamin C in the treatment regimen in many countries including Egypt [ 10 ]. AM has the potential to cause serious adverse effects. Headache, nausea, dizziness, stomach aches and hepatotoxicity were the most commonly reported side effects [ 8 ]. Also, according to a preceding study, AM is likely to cause abnormal cardiac activity [ 11 ]. Long-term usage of AM may result in antibiotic resistance and even mortality in individuals who suffer from allergy to it [ 12 ]. Different analytical and electrochemical methodologies for detecting AM were presented in several studies. For instance; Raghuram et al. used reversed-phase high performance liquid chromatography (RP-HPLC) [ 13 ], El-Adl et al. employed p-chloranilic acid in their spectrophotometric analysis [ 14 ], Chavada et al. utilized colorimetric sensing [ 15 ] and Guo et al. applied a fluorescent probe using nitrogen and sulfur co-doped carbon quantum dots [ 16 ]. These analytical approaches are unsatisfactory since they are time-consuming, want an expert for complex devices, incur excessive costs and demand preparation of the drug prior to analysis. However, electrochemical techniques were a superior alternative for these restrictions since they offer a simple electrode preparation, high sensitivity, prompt response, and are affordable and timesaving. For example; Stoian et al., Rebelo et al., Zhou et al. and Jafari et al. utilized molecularly imprinted polymers (MIPs) [ 17 – 20 ], Vajdle et al. employed a silver-amalgam film electrode [ 21 ], Sharma et al. used zinc vanadate/phosphorous doped reduced graphene oxide nanostructure [ 22 ]. These adjustments, however, produced quite reasonable results, but they have some flaws, such as the use of exorbitant raw materials, complex construction of the working electrodes and engaging with hazardous metals. The choice to use CPE was rather satisfactory because it has several advantages as being affordable, easy to handle, safe and having minimal background currents over a wide array of potentials [ 23 ]. This study offers a new CPE modification that uses PT to detect AM. Threonine (Supplementary Scheme S1C) is a key component of numerous body proteins and is an essential amino acid. It, along with serine, is an immune-boosting nutrient and is one of the two proteinogenic amino acids with an alcohol group. Along with isoleucine, it is one of the two common amino acids containing a chiral side chain [ 24 ]. Electropolymerization has emerged as an effective and adaptable methodology for manufacturing customized electrodes. The application of thick polymer coatings provides an extremely high surface coverage, which gives this modification a lot of versatility. The surface of the PTCPE was analyzed using SEM and EIS. Various voltammetric techniques were used to test the feasibility of employing the PTCPE sensor to detect AM and it has proved its efficacy as being a sensitive, selective and simply fabricated electrode. The currently proposed electrochemical sensor responded effectively to pharmaceutical samples. 2. Experimental 2.1. Chemicals AM in its pure state and methanol (for HPLC ≥ 99.9%) were purchased from Sigma-Aldrich to prepare a 10 mM AM stock solution. potassium ferrocyanide, potassium chloride and graphite micro-particles (< 50 µm, for the CPE preparation) were obtained from Merck, Darmstadt, Germany. Paraffin oil was bought from Aldrich, USA. Sodium hydroxide was obtained from the International Trade Association (ITA). Sodium dihydrogen orthophosphate and disodium hydrogen orthophosphate were obtained from El Nasr Pharmaceutical Chemicals Co. (ADWIC) for the preparation of 0.1 M, pH 7.0 PBS. L-Threonine (˃ 99.0% − 101.0%) was purchased from Bio Basic Inc. AM’s medicinal samples (Zithrokan capsules, Hikma pharmaceuticals, Cairo, Egypt) were purchased from a local pharmacy. Many pharmaceutical medications were employed in the interference test, including Cephalexin (Ceporex tablets, GlaxoSmithKline (GSK), Cairo, Egypt), Clarithromycin (KLACID XL tablets, Abbott, Cairo, Egypt) and Paracetamol (Sigma-Aldrich). Urea, starch, sucrose and glucose were bought from MISR-Scientific Company. 2.2. Apparatuses and methods All electrochemical assays, including CV, SWV and EIS, were carried out under the same circumstances as in our earlier study [ 25 ]. The pH was adjusted using an Adwa 1030 digital pH meter (Romania). The surface structure and arrangement of the electrode were investigated using SEM (Model Quanta 250 Field Emission Gun). 2.3. PTCPE sensor fabrication At first, carbon paste (CP) was prepared by hand mingling of 3.0 g graphite powder with an appropriate amount of paraffin oil in a mortar for 10 minutes to get a consistent paste. Then, to obtain a CPE, this paste was inserted into a 3.0 mm diameter hole at the tip of a Teflon tube. Subsequently, the electrode’s surface was then pressed utilizing sandpaper. Eventually, the polymeric layer of PT formed on the surface of the CP was attained by means of a CV in the potential range of − 0.6 to 2.3 V with a scan rate of 0.1 V/s for 30 scan cycles in PBS of pH 9.0 in the existence of L-threonine with a concentration equals 2.5 mM. After that, the resultant adapted electrode was washed with distilled water and then air-dried to be available for assessing AM [ 26 ]. 2.4. Pharmaceutical samples preparation One 500 mg AM capsule was emptied into 250 ml distilled water and prepared as previously stated in our work [ 27 ]. 3. Results and discussion 3.1. Electropolymerization of L-Threonine on the surface of CPE The outcome of the number of electropolymerization cycles was inspected by scanning the electrode within a potential range of − 0.6 to 2.3 V at a scan rate of 0.1 V/s for 30 scan cycles in PBS of pH 9.0 as revealed in Fig. 1 A. The variation of the peak current versus the number of scan cycles is shown in Fig. 1 B. The current values amplified with increasing the number of cycles from 10.0 to 30.0 and then decayed. The uppermost was obtained for 30.0 scan cycles, so it was employed for the electropolymerization of L-Threonine on the CPE surface. 3.2. Surface characterization The surface morphology of PTCPE is demonstrated in Supplementary Fig. S1 with a cotton needles like surface with a uniform arrangement confirming the successful electropolymerization of L-Threonine on the surface of the CPE. 3.3. Electrochemical functioning of AM at the surface of the PTCPE To optimize any electrochemical sensor, it is vital to understand how it reacts with AM when compared to BCPE. The CV technique was used to test the sensitivity and validity of employing the PTCPE to detect AM. At a scan rate of 0.05 V.s − 1 , the CVs of BCPE and PTCPE in PBS (0.1 M, pH 7.4) with 1.0 mM AM are shown in Fig. 2 A. The oxidation of AM on PTCPE appears to be an irreversible process with two distinct oxidation peaks, the first at around 0.8 V, while the second happens at a more positive potential of around 1.0 V. These peaks can be justified by the fact that the AM molecule is adsorbed on the surface of PTCPE, where it go through electro-oxidation by losing an electron from the nitrogen atom in the desosamine sugar residue, forming a radical cation, and then protonation of this nitrogen by drawing a proton from the water residue in the media. Because this final state is electro-inactive, no more oxidation happens (Scheme 1 ). According to the theory that the electro-oxidation of AM is followed by a quick chemical reaction and a second electron-transfer step (ECE mechanism), a second peak arises at a greater positive potential, due to the oxidation of the chemical reaction's byproducts [ 28 ]. EIS analyses, which encompass both Bode and Nyquist plots (Fig. 2 B&C, respectively), are a convincing tool for approving the CV data and ensuring that PTCPE has a higher electro-catalytic activity than BCPE for the oxidation of 1.0 mM AM. The Nyquist plot for BCPE is a straight line while that for PTCPE is mainly a straight line with an insignificant semi-circle part signifying that the development is primarily diffusion-dependent with a slight charge-transfer reliance. The data are clearly illustrated by the model shown in Fig. 2 D with a moderate error of 1%. Where; R1 reflects the solution’s resistance, C is the double layer capacitance, which is linked in parallel to R2 "the outer layers’ resistance", Q is the constant phase element which is also linked in parallel to W "the Warburg component related to the diffusion process". An empirical coefficient (α = 0 to 1) explains the deviation from the capacitive ideality as a consequence of surface roughness, α = 1 stands for an ideal capacitor and α = 0.5 stands for a diffusion behavior. For the two electrodes, PTCPE and BCPE, The best-fitting values are listed in Table 1 . The value of R1 is relatively constant for each electrode. The greater capacitance values and lower impedance values of PTCPE when compared to BCPE imply a stronger conducting performance and guarantee the high oxidation peak current found in the CV data. Table 1 EIS data of 1.0 mM AM in 0.1 M PBS at the surface of PTCPE and BCPE. R 1 +(C/R 2 )+(Q/W) Value PTCPE BCPE R 1 (kΩ) 0.32 0.36 C (µF) 260 7.46 R 2 (kΩ) 0.156 2660 Q (µF) 629.5 10.24 W (MΩ.s − 1/2 ) 272 376 3.4. Influence of solution pH The effect of adjusting pH on the electro-oxidation of 1 mM AM in 0.1 M PBS (pH 5.0–10.0) at PTCPE was exhibited using the CV technique (Fig. 3 A). The electro-oxidation of AM is clearly pH-dependent as the current peak widens and begins to disappear in acidic medium (pH 5.0), which is due to the AM molecule being protonated and the fact that AM is only electro-active when it is not protonated. As the pH upsurges, an ideal peak emerges. For this work, pH 7.4 was applied to imitate the physiological pH of the human body. The current surges on going from pH 5.0 to 8.0, according to the influence of pH on the current peak (Fig. 3 B), and subsequently collapses at higher pH values, confirming the mechanism of AM protonation in acidic medium while remaining electro-inactive. Because AM has a pKa value of 8.7, it is understandable why the present peak values for the pH range 7.0–8.0 are relatively high. Nyquist plot (Fig. 3 C) conforms to the CV’s outcomes for changing the pH of PBS. It shows that pH 7.4 acquires the lowermost impedance value with the highest conductivity. The relationship between pH and peak potential is shown to be linear in Fig. 3 D, providing the following equation: E p (V) = 1.26 − 0.05 pH (r 2 = 0.95) This demonstrates that the electro-oxidation of AM requires a proton-transfer phase and that the anodic peak potential is dependent on pH. The slope (0.05 V/pH) matches the ideal nernestian slope at 25 ֩C (0.059 V/pH), proving that the same number of protons and electrons were exchanged during the electrochemical oxidation. 3.5. Influence of scan rate The CV approach in Fig. 4 A illustrates how the scan rate affects the anodic peak current of AM with 1.0 mM concentration in PBS (0.1 M). The peak current escalates and the peak potential shifts to higher affirmative values as the scan rate upsurges from 0.01 to 0.2 V.s − 1 , viewing an irreversible electrochemical oxidation. According to Fig. 4 B, there is a linearity amongst the anodic peak current and the square root of the scan rate, declaring the existence of a diffusion-controlled mechanism, this linear relation is illustrated by: I (µA) = 3.05 υ 1/2 + 8.02; r 2 = 0.98 for BCPE , I (µA) = 13.99 υ 1/2 – 23.46; r 2 = 0.97 for PTCPE , The excellent usage of CPE for adsorbing particles on its active surface during the electrode reaction is reflected in a linearity amongst log I versus log ν with a slope of 0.62 (Fig. 4 C), which denotes an adsorption-controlled mechanism. Thus, it is a miscellaneous diffusion-adsorption mechanism overall. These outcomes are in line with the literature on the AM’s transport characteristics at other modified electrodes [ 29 ]. The kinetic factors are generated using Laviron model (Eq. 1) from Fig. 4 D, which depicts a linear relationship amongst the peak potential and the logarithm of the scan rate represented as following [ 30 ]: E pa = E 0 + 2.3 RT / [(1- α) nF] × log ν (1) E pa (V) = 1.06 + 0.20 log ν (V.s − 1 ) (r 2 = 0.96) Where; α is the electron-transfer factor, which for irreversible processes ranges between 0.4 and 0.6 [ 31 ] and n is the number of electrons transferred in the electro-oxidation reaction, which is estimated from Eq. (1) to be roughly 1.0 for AM. Applying the Randles-Sevcik equation (Eq. 2), the active surface area of PTCPE was calculated using the CV technique in 1 mM K 4 Fe(CN) 6 and 0.1 M KCl as an electrolyte [ 32 ]: I pa = (2.69×10 5 ) n 3/2 ACD 1/2 ν 1/2 (2) Where; I pa is the anodic peak current (A), n is the number of transferred electrons through the redox process and n = 1, A is the electrode’s electro-active area (cm 2 ), C is the concentration of K 4 Fe(CN) 6 (mol.cm − 3 ), D is the diffusion coefficient (cm 2 .s − 1 ) equal to 7.6×10 − 6 , and ν is the scan rate (V.s − 1 ). The electro-active area is determined to be 0.05 cm 2 for the BCPE, and 0.15 cm 2 for the PTCPE. According to Eq. (2), (2.69×10 5 ) n 3/2 ACD 1/2 corresponds to the slope in Fig. 4 B and by substituting with the estimated area; both BCPE and PTCPE are thought to have diffusion coefficients of 51.42×10 − 3 and 120.21×10 − 3 cm 2 .s − 1 respectively. Thus, the addition of PT to the sensor dramatically improved the AM molecules’ diffusion through the electrolyte and enlarged the active surface area by a factor of 3. 3.6. Influence of accumulation time CVs for 1.0 mM AM in PBS (0.1 M, pH 7.4) were performed over various time intervals to investigate the response of PTCPE (Supplementary Fig. S2). The anodic peak currents surged when the sensor’s immersion time was enlarged until reaching a plateau after nearly 140 min, which is considered to be the optimal time for the electrode stability. 3.7. Calibration curve study A linearity among anodic peak current and multiple AM concentrations (Fig. 5 ) confirms the sensitivity of PTCPE for electro-detection of AM and it can be expressed by the linear equation: I (µA) = 2.50 + 9.31×10 − 3 C (µM) (r 2 = 0.97) The associated SWV curves for rising AM concentration from 8.88 up to 1000.0 µM in PBS (0.1 M, pH 7.4) and scan rate 0.01 V.s − 1 using PTCPE are shown in the inset of Fig. 5 . The following equations (3&4) are used to compute the limit of detection (LOD) and limit of quantification (LOQ) [ 33 , 34 ]: LOD = 3s/m (3) & LOQ = 10s/m (4) and it was discovered that they were 0.32 and 1.07 µM, respectively, proving the electrode’s sensitivity. A relative standard deviation (RSD) of 1.43% was obtained after repeating the measurements five times under the identical circumstances to test the suggested electrode's repeatability. Table 2 provides a comparative analysis of some of the formerly reported techniques for AM detection. Nevertheless, these methods require the use of expensive or toxic chemicals, in addition to being more difficult to fabricate than the edited electrode presented here. Thus, this method demonstrated its dependability and sensitivity for AM detection with a relatively low detection limit and great selectivity. Table 2 PTCPE against other analytical and electrochemical methods in the literature. Method Electrode’s material Linear range (µM) LOD (µM) Reference Spectrophotometric analysis - 6.68–66.76 1.60 [ 14 ] Colorimetric sensing - 0.2–20 0.05 [ 15 ] HPLC – ELSD a - 67.9-679.9 9.01 [ 35 ] RP-HPLC b - 33.38-367.16 16.69 [ 13 ] DPV c MIP/SPCE d 0.5–10.0 0.08 [ 18 ] SWV Hg(Ag)FE e 6.42–31.11 1.92 [ 21 ] DPV MIP/ABP f 0.10–20.0 0.01 [ 19 ] DPV FSCPE g 44-1000 11 [ 27 ] SWV PTCPE 8.88-1×10 3 0.32 This work a HPLC – ELSD: high performance liquid chromatography coupled with an evaporative light scattering detector; b RP-HPLC: reversed-phase- high performance liquid chromatography; c DPV: differential pulse voltammetry; d MIP/SPCE: molecularly imprinted polymer on a screen-printed carbon electrode; e Hg(Ag)FE: silver-amalgam film electrode; f MIP/ABP: molecularly imprinted polymer/acetylene black-mod carbon paste; g FSCPE: fumed silica carbon paste electrode. 3.8. Commercial samples study The sensor’s feasibility was assessed by detecting AM in pharmaceutical samples using SWV, by spiking the samples with standard AM concentrations applying a standard addition method. Supplementary Table S1 displays the results, which confirm that the modified electrode can accurately measure AM in pharmaceutical samples with recoveries of 99.03–103.22% and RSDs of 1.0% – 3.4% for all samples. To evaluate the level of AM in the real samples, each measurement was performed with an average of five replicate trials. 3.9. PTCPE's long-term stability, repeatability, and interference study Supplementary Table S2 provides an illustration of how different interfering substances affect PTCPE's ability to detect AM. This was accomplished by loading equal and double amounts of several substances, such as urea, sucrose, glucose, starch, and paracetamol, into a fixed concentration of AM (600 µM). To confirm the selectivity of the suggested technique against AM, it was evaluated using the same experimental settings with other antibiotics and structurally related drugs such as erythromycin, clarithromycin, ciprofloxacin, cefixime, and cephalexin. As a recommended protocol for handling COVID-19 patients, paracetamol is commonly used with AM, so it is essential to examine the PTCPE’s selectivity for it. The sensor was competent for detecting both of them at distinct peak potentials of 0.36 V and 0.80 V for paracetamol and AM, respectively (Supplementary Fig. S3) without altering the sensor’s response to AM, demonstrating the sensor’s great selectivity. Five sequent voltammetric determinations for 50 µM of AM with an RSD of 1.5% were performed to validate the reproducibility of PTCPE in terms of RSD, guaranteeing the precision of the electrode under investigation. The PTCPE was kept at room temperature for 12 days to examine its long-term stability. The sensor was then subjected to a single voltammetric measurement for AM, which revealed a current response of 97% of the value recorded right after fresh fabrication, indicating good electrode storage consistency. 4. Conclusion Based on the adjustment of CPE with PT, this work presented a sensitive and selective electrochemical sensor for identifying AM. To achieve the most sensitive determination of AM, a variety of electrochemical approaches were used to improve the experimental conditions. With a wide linear range of 8.88 – 1000.0 µM of AM and a LOD of 0.32 µM, the newly manufactured sensor demonstrated its effectiveness in detection. The proposed approach was easy to use, inexpensive and sensitive enough to detect AM in medicinal capsules under physiological circumstances. Declarations Author contributions S. Mamdouh: Did the experimental work, converted the obtained data into various figures using SigmaPlot 10.0 and ChemDraw Professional 16.0, and suggested the electro-oxidation mechanism of the drug. M. Shehata: Wrote the statistical analysis of the work, supplied the used chemicals, and helped in revising the manuscript. A.M. Fekry: Interpreted the data, demonstrated the EIS data, and wrote the SEM characterization. M.A.Ameer (corresponding author) : Interpreted and reviewed all data All authors reviewed the manuscript. Data availability statement The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Competing Interests Statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. References Zuckerman, J.M. Macrolides and ketolides: Azithromycin, clarithromycin, telithromycin. Infect. Dis. Clin. 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Supplementarydata.doc Cite Share Download PDF Status: Published Journal Publication published 06 Jan, 2025 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 28 Oct, 2024 Reviews received at journal 10 Oct, 2024 Reviewers agreed at journal 05 Oct, 2024 Reviews received at journal 24 Jul, 2024 Reviewers agreed at journal 24 Jul, 2024 Reviewers agreed at journal 23 Jul, 2024 Reviewers invited by journal 23 Jul, 2024 Editor assigned by journal 23 Jul, 2024 Editor invited by journal 23 Jul, 2024 Submission checks completed at journal 19 Jul, 2024 First submitted to journal 14 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4737822","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":337517826,"identity":"3f41c99e-141b-423d-b392-68884eca86ea","order_by":0,"name":"salma mamdouh","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"prefix":"","firstName":"salma","middleName":"","lastName":"mamdouh","suffix":""},{"id":337517827,"identity":"7ad3e556-d500-4f4d-ad73-5617d6e3bc07","order_by":1,"name":"mohammed shehata","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"prefix":"","firstName":"mohammed","middleName":"","lastName":"shehata","suffix":""},{"id":337517828,"identity":"9823eab0-18df-44d8-8705-407b7100992a","order_by":2,"name":"amany fekry","email":"","orcid":"","institution":"Cairo University","correspondingAuthor":false,"prefix":"","firstName":"amany","middleName":"","lastName":"fekry","suffix":""},{"id":337517829,"identity":"326ef4d3-56e7-49c3-a6ac-7d0e2af4a005","order_by":3,"name":"magda ameer","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYFAD9gYGZhK18BwgWYtEApFadNtPJz74uIdBTj7yjeHnggobBv727gS8WszO5G42nPGMwdjwdo6x9IwzaQwSZ85uwK/lQO42aaA3EjfOzjGQ5m07zGAgkUtAy/m323//OcBQv3HmGePfxGm5kbuNmeEAQ4K8BI8ZkbbceLtZsucAg+EGnrQya54zaTyE/XI+d+OHHwcY5OXbD2++zVNhI8ff3otfCxT8ZzA4wGEAYvEQoxwC5BvYHxCvehSMglEwCkYUAAD7NEgvHefbAwAAAABJRU5ErkJggg==","orcid":"","institution":"Cairo University","correspondingAuthor":true,"prefix":"","firstName":"magda","middleName":"","lastName":"ameer","suffix":""}],"badges":[],"createdAt":"2024-07-14 09:30:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4737822/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4737822/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-79614-6","type":"published","date":"2025-01-06T15:56:53+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":62375509,"identity":"9da38886-ef04-4b13-bd4c-d5f35148b57a","added_by":"auto","created_at":"2024-08-13 13:07:17","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":45384,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) Electropolymerization of L-Threonine on CPE for 30.0 cycles. (B) Effect of the number of cycles on the anodic current.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4737822/v1/382ec1952753787da78c9338.jpg"},{"id":62375511,"identity":"95551959-2587-449c-9aa8-66937901cf43","added_by":"auto","created_at":"2024-08-13 13:07:17","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":75265,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) AM CVs in pH 7.4 PBS (0.1 M) with a scan rate of 0.05 V/s at BCPE and PTCPE. (B, C) EIS analysis at 1.0 mM AM in pH 7.4 PBS (0.1 M) (Bode and Nyquist plots, respectively). (C. inset: Nyquist plot with high amplification). (D) The equivalent circuit with the best performance.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4737822/v1/e46319c7ca9b0068b0771efe.jpg"},{"id":62375510,"identity":"376cd123-52dc-4ca2-af24-48cf594f3503","added_by":"auto","created_at":"2024-08-13 13:07:17","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":83000,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) CVs of 1.0 mM AM in PBS 0.1 M at varying pH values (5.0-10.0) scanned at 0.05 V/s. (B) The anodic current related to the pH for PTCPE. (C) Nyquist plots of 1.0 mM AM at varying pH values. (D) The effect of pH on the anodic potential of AM at PTCPE.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4737822/v1/bad9edd1e1591a584f479ce9.jpg"},{"id":62376074,"identity":"01744aed-89aa-4cae-816f-a3273b4424b4","added_by":"auto","created_at":"2024-08-13 13:15:17","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":93118,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(A) CVs of 1.0 mM AM in pH 7.4 PBS at varying scan rates (0.01-0.2 V/s). (B) The anodic peak current versus the square root of scan rate at BCPE and PTCPE. (C) The logarithm of the anodic current related to the logarithm of the scan rate at PTCPE. (D) The anodic potentials plotted versus the\u003c/strong\u003e \u003cstrong\u003elogarithm of the scan rate at PTCPE.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4737822/v1/6a6b753d64efdc4c3fa928a5.jpg"},{"id":62375513,"identity":"cd22c1e6-fdb7-438d-8710-04af80afa204","added_by":"auto","created_at":"2024-08-13 13:07:18","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":54994,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe calibration diagram of AM in PBS (pH 7.4) using PTCPE. Inset: the equivalent curves for rising AM concentrations using SWV at scan rate 0.01 V.s\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e-1\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4737822/v1/4d15c513b7f39796fa48d621.jpg"},{"id":73693895,"identity":"a04867b9-2c57-4f38-b0de-c3ca98a5c6cf","added_by":"auto","created_at":"2025-01-13 16:09:08","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1637131,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4737822/v1/2b382e6e-1dd2-43f3-9052-cd9ef96fb74f.pdf"},{"id":62376075,"identity":"e23f04e4-67de-4a7e-ae66-eeefb7b2b866","added_by":"auto","created_at":"2024-08-13 13:15:18","extension":"jpg","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":20762,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eScheme 1.\u003c/strong\u003e \u003cstrong\u003eElectro-oxidation mechanism of AM on PTCPE.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"scheme1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4737822/v1/74d21246b0a13a99f8bcb750.jpg"},{"id":62375515,"identity":"2870f9c1-5668-49aa-a19b-180c834cdd5a","added_by":"auto","created_at":"2024-08-13 13:07:18","extension":"doc","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":621056,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarydata.doc","url":"https://assets-eu.researchsquare.com/files/rs-4737822/v1/bf1cc1893031cf72848bc139.doc"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eElectro-polymerization of modified carbon paste sensor for detecting Azithromycin \u003c/p\u003e","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eThe semisynthetic macrolide antibiotic AM (9-Deoxo-9a-aza-9a-methyl-9a-homoerythromycin A) (Supplementary Scheme S1A) is generated by remodeling the naturally occurring antibiotic, erythromycin (Supplementary Scheme S1B) through replacing the carbonyl group at the 9a site of the aglycone ring by a methyl-substituted nitrogen resultant in a 15-membered ring termed as an azalide [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. AM exhibits a broad spectrum of antibacterial activity, as a result, it is typically used to treat a wide range of mild-to-moderate bacterial infections. As well as its antibacterial effects, AM has been reported to have antiviral properties in vitro and/or in vivo against a variety of viruses, including Ebola [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], Zika [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and influenza H1N1 virus [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. AM also manifests an antiviral activity against SARS-CoV-2 [\u003cspan additionalcitationids=\"CR6 CR7 CR8\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The world health organization (WHO) described COVID-19 as a global pandemic that has produced millions of fatalities globally. AM detection in real samples is important as being one of the prescribed medications alongside paracetamol, zinc and vitamin C in the treatment regimen in many countries including Egypt [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. AM has the potential to cause serious adverse effects. Headache, nausea, dizziness, stomach aches and hepatotoxicity were the most commonly reported side effects [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Also, according to a preceding study, AM is likely to cause abnormal cardiac activity [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Long-term usage of AM may result in antibiotic resistance and even mortality in individuals who suffer from allergy to it [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Different analytical and electrochemical methodologies for detecting AM were presented in several studies. For instance; Raghuram et al. used reversed-phase high performance liquid chromatography (RP-HPLC) [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], El-Adl et al. employed p-chloranilic acid in their spectrophotometric analysis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], Chavada et al. utilized colorimetric sensing [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] and Guo et al. applied a fluorescent probe using nitrogen and sulfur co-doped carbon quantum dots [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These analytical approaches are unsatisfactory since they are time-consuming, want an expert for complex devices, incur excessive costs and demand preparation of the drug prior to analysis.\u003c/p\u003e \u003cp\u003eHowever, electrochemical techniques were a superior alternative for these restrictions since they offer a simple electrode preparation, high sensitivity, prompt response, and are affordable and timesaving. For example; Stoian et al., Rebelo et al., Zhou et al. and Jafari et al. utilized molecularly imprinted polymers (MIPs) [\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], Vajdle et al. employed a silver-amalgam film electrode [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], Sharma et al. used zinc vanadate/phosphorous doped reduced graphene oxide nanostructure [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. These adjustments, however, produced quite reasonable results, but they have some flaws, such as the use of exorbitant raw materials, complex construction of the working electrodes and engaging with hazardous metals.\u003c/p\u003e \u003cp\u003eThe choice to use CPE was rather satisfactory because it has several advantages as being affordable, easy to handle, safe and having minimal background currents over a wide array of potentials [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study offers a new CPE modification that uses PT to detect AM. Threonine (Supplementary Scheme S1C) is a key component of numerous body proteins and is an essential amino acid. It, along with serine, is an immune-boosting nutrient and is one of the two proteinogenic amino acids with an alcohol group. Along with isoleucine, it is one of the two common amino acids containing a chiral side chain [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Electropolymerization has emerged as an effective and adaptable methodology for manufacturing customized electrodes. The application of thick polymer coatings provides an extremely high surface coverage, which gives this modification a lot of versatility. The surface of the PTCPE was analyzed using SEM and EIS. Various voltammetric techniques were used to test the feasibility of employing the PTCPE sensor to detect AM and it has proved its efficacy as being a sensitive, selective and simply fabricated electrode. The currently proposed electrochemical sensor responded effectively to pharmaceutical samples.\u003c/p\u003e"},{"header":"2. Experimental","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Chemicals\u003c/h2\u003e \u003cp\u003eAM in its pure state and methanol (for HPLC\u0026thinsp;\u0026ge;\u0026thinsp;99.9%) were purchased from Sigma-Aldrich to prepare a 10 mM AM stock solution. potassium ferrocyanide, potassium chloride and graphite micro-particles (\u0026lt;\u0026thinsp;50 \u0026micro;m, for the CPE preparation) were obtained from Merck, Darmstadt, Germany. Paraffin oil was bought from Aldrich, USA. Sodium hydroxide was obtained from the International Trade Association (ITA). Sodium dihydrogen orthophosphate and disodium hydrogen orthophosphate were obtained from El Nasr Pharmaceutical Chemicals Co. (ADWIC) for the preparation of 0.1 M, pH 7.0 PBS. L-Threonine (˃ 99.0% \u0026minus;\u0026thinsp;101.0%) was purchased from Bio Basic Inc.\u003c/p\u003e \u003cp\u003eAM\u0026rsquo;s medicinal samples (Zithrokan capsules, Hikma pharmaceuticals, Cairo, Egypt) were purchased from a local pharmacy. Many pharmaceutical medications were employed in the interference test, including Cephalexin (Ceporex tablets, GlaxoSmithKline (GSK), Cairo, Egypt), Clarithromycin (KLACID XL tablets, Abbott, Cairo, Egypt) and Paracetamol (Sigma-Aldrich). Urea, starch, sucrose and glucose were bought from MISR-Scientific Company.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Apparatuses and methods\u003c/h2\u003e \u003cp\u003eAll electrochemical assays, including CV, SWV and EIS, were carried out under the same circumstances as in our earlier study [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The pH was adjusted using an Adwa 1030 digital pH meter (Romania). The surface structure and arrangement of the electrode were investigated using SEM (Model Quanta 250 Field Emission Gun).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3. PTCPE sensor fabrication\u003c/h2\u003e \u003cp\u003eAt first, carbon paste (CP) was prepared by hand mingling of 3.0 g graphite powder with an appropriate amount of paraffin oil in a mortar for 10 minutes to get a consistent paste. Then, to obtain a CPE, this paste was inserted into a 3.0 mm diameter hole at the tip of a Teflon tube. Subsequently, the electrode\u0026rsquo;s surface was then pressed utilizing sandpaper. Eventually, the polymeric layer of PT formed on the surface of the CP was attained by means of a CV in the potential range of \u0026minus;\u0026thinsp;0.6 to 2.3 V with a scan rate of 0.1 V/s for 30 scan cycles in PBS of pH 9.0 in the existence of L-threonine with a concentration equals 2.5 mM. After that, the resultant adapted electrode was washed with distilled water and then air-dried to be available for assessing AM [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4. Pharmaceutical samples preparation\u003c/h2\u003e \u003cp\u003eOne 500 mg AM capsule was emptied into 250 ml distilled water and prepared as previously stated in our work [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results and discussion","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Electropolymerization of L-Threonine on the surface of CPE\u003c/h2\u003e \u003cp\u003eThe outcome of the number of electropolymerization cycles was inspected by scanning the electrode within a potential range of \u0026minus;\u0026thinsp;0.6 to 2.3 V at a scan rate of 0.1 V/s for 30 scan cycles in PBS of pH 9.0 as revealed in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eA. The variation of the peak current versus the number of scan cycles is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003eB. The current values amplified with increasing the number of cycles from 10.0 to 30.0 and then decayed. The uppermost was obtained for 30.0 scan cycles, so it was employed for the electropolymerization of L-Threonine on the CPE surface.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Surface characterization\u003c/h2\u003e \u003cp\u003eThe surface morphology of PTCPE is demonstrated in Supplementary Fig. \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e with a cotton needles like surface with a uniform arrangement confirming the successful electropolymerization of L-Threonine on the surface of the CPE.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Electrochemical functioning of AM at the surface of the PTCPE\u003c/h2\u003e \u003cp\u003eTo optimize any electrochemical sensor, it is vital to understand how it reacts with AM when compared to BCPE. The CV technique was used to test the sensitivity and validity of employing the PTCPE to detect AM. At a scan rate of 0.05 V.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, the CVs of BCPE and PTCPE in PBS (0.1 M, pH 7.4) with 1.0 mM AM are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA. The oxidation of AM on PTCPE appears to be an irreversible process with two distinct oxidation peaks, the first at around 0.8 V, while the second happens at a more positive potential of around 1.0 V.\u003c/p\u003e \u003cp\u003eThese peaks can be justified by the fact that the AM molecule is adsorbed on the surface of PTCPE, where it go through electro-oxidation by losing an electron from the nitrogen atom in the desosamine sugar residue, forming a radical cation, and then protonation of this nitrogen by drawing a proton from the water residue in the media. Because this final state is electro-inactive, no more oxidation happens (Scheme \u003cspan refid=\"Sch1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). According to the theory that the electro-oxidation of AM is followed by a quick chemical reaction and a second electron-transfer step (ECE mechanism), a second peak arises at a greater positive potential, due to the oxidation of the chemical reaction's byproducts [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eEIS analyses, which encompass both Bode and Nyquist plots (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eB\u0026amp;C, respectively), are a convincing tool for approving the CV data and ensuring that PTCPE has a higher electro-catalytic activity than BCPE for the oxidation of 1.0 mM AM. The Nyquist plot for BCPE is a straight line while that for PTCPE is mainly a straight line with an insignificant semi-circle part signifying that the development is primarily diffusion-dependent with a slight charge-transfer reliance. The data are clearly illustrated by the model shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eD with a moderate error of 1%. Where; R1 reflects the solution\u0026rsquo;s resistance, C is the double layer capacitance, which is linked in parallel to R2 \"the outer layers\u0026rsquo; resistance\", Q is the constant phase element which is also linked in parallel to W \"the Warburg component related to the diffusion process\". An empirical coefficient (α\u0026thinsp;=\u0026thinsp;0 to 1) explains the deviation from the capacitive ideality as a consequence of surface roughness, α\u0026thinsp;=\u0026thinsp;1 stands for an ideal capacitor and α\u0026thinsp;=\u0026thinsp;0.5 stands for a diffusion behavior. For the two electrodes, PTCPE and BCPE, The best-fitting values are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The value of R1 is relatively constant for each electrode. The greater capacitance values and lower impedance values of PTCPE when compared to BCPE imply a stronger conducting performance and guarantee the high oxidation peak current found in the CV data.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eEIS data of 1.0 mM AM in 0.1 M PBS at the surface of PTCPE and BCPE.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eR\u003csub\u003e1\u003c/sub\u003e+(C/R\u003csub\u003e2\u003c/sub\u003e)+(Q/W)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eValue\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePTCPE\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBCPE\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR\u003csub\u003e1\u003c/sub\u003e (kΩ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC (\u0026micro;F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.46\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eR\u003csub\u003e2\u003c/sub\u003e (kΩ)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.156\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2660\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQ (\u0026micro;F)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e629.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eW (MΩ.s\u003csup\u003e\u0026minus;\u0026thinsp;1/2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e272\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e376\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e3.4. Influence of solution pH\u003c/h2\u003e \u003cp\u003eThe effect of adjusting pH on the electro-oxidation of 1 mM AM in 0.1 M PBS (pH 5.0\u0026ndash;10.0) at PTCPE was exhibited using the CV technique (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA). The electro-oxidation of AM is clearly pH-dependent as the current peak widens and begins to disappear in acidic medium (pH 5.0), which is due to the AM molecule being protonated and the fact that AM is only electro-active when it is not protonated. As the pH upsurges, an ideal peak emerges. For this work, pH 7.4 was applied to imitate the physiological pH of the human body.\u003c/p\u003e \u003cp\u003eThe current surges on going from pH 5.0 to 8.0, according to the influence of pH on the current peak (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eB), and subsequently collapses at higher pH values, confirming the mechanism of AM protonation in acidic medium while remaining electro-inactive. Because AM has a pKa value of 8.7, it is understandable why the present peak values for the pH range 7.0\u0026ndash;8.0 are relatively high.\u003c/p\u003e \u003cp\u003eNyquist plot (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC) conforms to the CV\u0026rsquo;s outcomes for changing the pH of PBS. It shows that pH 7.4 acquires the lowermost impedance value with the highest conductivity.\u003c/p\u003e \u003cp\u003eThe relationship between pH and peak potential is shown to be linear in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eD, providing the following equation: \u003cb\u003eE\u003c/b\u003e\u003csub\u003e\u003cb\u003ep\u003c/b\u003e\u003c/sub\u003e \u003cb\u003e(V)\u0026thinsp;=\u0026thinsp;1.26\u0026thinsp;\u0026minus;\u0026thinsp;0.05 pH (r\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.95)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThis demonstrates that the electro-oxidation of AM requires a proton-transfer phase and that the anodic peak potential is dependent on pH. The slope (0.05 V/pH) matches the ideal nernestian slope at 25 ֩C (0.059 V/pH), proving that the same number of protons and electrons were exchanged during the electrochemical oxidation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e3.5. Influence of scan rate\u003c/h2\u003e \u003cp\u003eThe CV approach in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eA illustrates how the scan rate affects the anodic peak current of AM with 1.0 mM concentration in PBS (0.1 M). The peak current escalates and the peak potential shifts to higher affirmative values as the scan rate upsurges from 0.01 to 0.2 V.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e, viewing an irreversible electrochemical oxidation.\u003c/p\u003e \u003cp\u003eAccording to Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB, there is a linearity amongst the anodic peak current and the square root of the scan rate, declaring the existence of a diffusion-controlled mechanism, this linear relation is illustrated by:\u003c/p\u003e \u003cp\u003e \u003cb\u003eI (\u0026micro;A)\u0026thinsp;=\u0026thinsp;3.05 υ\u003c/b\u003e \u003csup\u003e \u003cb\u003e1/2\u003c/b\u003e \u003c/sup\u003e\u0026thinsp;\u003cb\u003e+\u0026thinsp;8.02; r\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.98 for BCPE\u003c/b\u003e,\u003c/p\u003e \u003cp\u003e \u003cb\u003eI (\u0026micro;A)\u0026thinsp;=\u0026thinsp;13.99 υ\u003c/b\u003e \u003csup\u003e \u003cb\u003e1/2\u003c/b\u003e \u003c/sup\u003e \u003cb\u003e\u0026ndash; 23.46; r\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.97 for PTCPE\u003c/b\u003e,\u003c/p\u003e \u003cp\u003eThe excellent usage of CPE for adsorbing particles on its active surface during the electrode reaction is reflected in a linearity amongst log I versus log ν with a slope of 0.62 (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eC), which denotes an adsorption-controlled mechanism. Thus, it is a miscellaneous diffusion-adsorption mechanism overall. These outcomes are in line with the literature on the AM\u0026rsquo;s transport characteristics at other modified electrodes [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe kinetic factors are generated using Laviron model (Eq.\u0026nbsp;1) from Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eD, which depicts a linear relationship amongst the peak potential and the logarithm of the scan rate represented as following [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e \u003cb\u003eE\u003c/b\u003e \u003csub\u003e \u003cb\u003epa\u003c/b\u003e \u003c/sub\u003e \u003cb\u003e= E\u003c/b\u003e\u003csup\u003e\u003cb\u003e0\u003c/b\u003e\u003c/sup\u003e \u003cb\u003e+ 2.3 RT / [(1- α) nF] \u0026times; log ν (1)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e \u003cb\u003eE\u003c/b\u003e \u003csub\u003e \u003cb\u003epa\u003c/b\u003e \u003c/sub\u003e \u003cb\u003e(V)\u0026thinsp;=\u0026thinsp;1.06\u0026thinsp;+\u0026thinsp;0.20 log ν (V.s\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026minus;\u0026thinsp;1\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e) (r\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.96)\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eWhere; α is the electron-transfer factor, which for irreversible processes ranges between 0.4 and 0.6 [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] and n is the number of electrons transferred in the electro-oxidation reaction, which is estimated from Eq.\u0026nbsp;(1) to be roughly 1.0 for AM.\u003c/p\u003e \u003cp\u003eApplying the Randles-Sevcik equation (Eq.\u0026nbsp;2), the active surface area of PTCPE was calculated using the CV technique in 1 mM K\u003csub\u003e4\u003c/sub\u003eFe(CN)\u003csub\u003e6\u003c/sub\u003e and 0.1 M KCl as an electrolyte [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]:\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003e \u003cb\u003eI\u003c/b\u003e \u003csub\u003e \u003cb\u003epa\u003c/b\u003e \u003c/sub\u003e \u003cb\u003e= (2.69\u0026times;10\u003c/b\u003e\u003csup\u003e\u003cb\u003e5\u003c/b\u003e\u003c/sup\u003e\u003cb\u003e) n\u003c/b\u003e\u003csup\u003e\u003cb\u003e3/2\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eACD\u003c/b\u003e\u003csup\u003e\u003cb\u003e1/2\u003c/b\u003e\u003c/sup\u003e \u003cb\u003eν\u003c/b\u003e\u003csup\u003e\u003cb\u003e1/2\u003c/b\u003e\u003c/sup\u003e \u003cb\u003e(2)\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eWhere; I\u003csub\u003epa\u003c/sub\u003e is the anodic peak current (A), n is the number of transferred electrons through the redox process and n\u0026thinsp;=\u0026thinsp;1, A is the electrode\u0026rsquo;s electro-active area (cm\u003csup\u003e2\u003c/sup\u003e), C is the concentration of K\u003csub\u003e4\u003c/sub\u003eFe(CN)\u003csub\u003e6\u003c/sub\u003e (mol.cm\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e), D is the diffusion coefficient (cm\u003csup\u003e2\u003c/sup\u003e.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) equal to 7.6\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;6\u003c/sup\u003e, and ν is the scan rate (V.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e). The electro-active area is determined to be 0.05 cm\u003csup\u003e2\u003c/sup\u003e for the BCPE, and 0.15 cm\u003csup\u003e2\u003c/sup\u003e for the PTCPE.\u003c/p\u003e \u003cp\u003eAccording to Eq.\u0026nbsp;(2), (2.69\u0026times;10\u003csup\u003e5\u003c/sup\u003e) n\u003csup\u003e3/2\u003c/sup\u003eACD\u003csup\u003e1/2\u003c/sup\u003e corresponds to the slope in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eB and by substituting with the estimated area; both BCPE and PTCPE are thought to have diffusion coefficients of 51.42\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e and 120.21\u0026times;10\u003csup\u003e\u0026minus;\u0026thinsp;3\u003c/sup\u003e cm\u003csup\u003e2\u003c/sup\u003e.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e respectively. Thus, the addition of PT to the sensor dramatically improved the AM molecules\u0026rsquo; diffusion through the electrolyte and enlarged the active surface area by a factor of 3.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.6. Influence of accumulation time\u003c/h2\u003e \u003cp\u003eCVs for 1.0 mM AM in PBS (0.1 M, pH 7.4) were performed over various time intervals to investigate the response of PTCPE (Supplementary Fig. S2). The anodic peak currents surged when the sensor\u0026rsquo;s immersion time was enlarged until reaching a plateau after nearly 140 min, which is considered to be the optimal time for the electrode stability.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.7. Calibration curve study\u003c/h2\u003e \u003cp\u003eA linearity among anodic peak current and multiple AM concentrations (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) confirms the sensitivity of PTCPE for electro-detection of AM and it can be expressed by the linear equation:\u003c/p\u003e \u003cp\u003e \u003cb\u003eI (\u0026micro;A)\u0026thinsp;=\u0026thinsp;2.50\u0026thinsp;+\u0026thinsp;9.31\u0026times;10\u003c/b\u003e \u003csup\u003e \u003cb\u003e\u0026minus;\u0026thinsp;3\u003c/b\u003e \u003c/sup\u003e \u003cb\u003eC (\u0026micro;M) (r\u003c/b\u003e\u003csup\u003e\u003cb\u003e2\u003c/b\u003e\u003c/sup\u003e\u0026thinsp;\u003cb\u003e=\u0026thinsp;0.97)\u003c/b\u003e\u003c/p\u003e \u003cp\u003eThe associated SWV curves for rising AM concentration from 8.88 up to 1000.0 \u0026micro;M in PBS (0.1 M, pH 7.4) and scan rate 0.01 V.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e using PTCPE are shown in the inset of Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. The following equations (3\u0026amp;4) are used to compute the limit of detection (LOD) and limit of quantification (LOQ) [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]:\u003c/p\u003e \u003cp\u003e \u003cb\u003eLOD\u0026thinsp;=\u0026thinsp;3s/m (3) \u0026amp; LOQ\u0026thinsp;=\u0026thinsp;10s/m (4)\u003c/b\u003e \u003c/p\u003e \u003cp\u003eand it was discovered that they were 0.32 and 1.07 \u0026micro;M, respectively, proving the electrode\u0026rsquo;s sensitivity. A relative standard deviation (RSD) of 1.43% was obtained after repeating the measurements five times under the identical circumstances to test the suggested electrode's repeatability.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e provides a comparative analysis of some of the formerly reported techniques for AM detection. Nevertheless, these methods require the use of expensive or toxic chemicals, in addition to being more difficult to fabricate than the edited electrode presented here. Thus, this method demonstrated its dependability and sensitivity for AM detection with a relatively low detection limit and great selectivity.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePTCPE against other analytical and electrochemical methods in the literature.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethod\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eElectrode\u0026rsquo;s material\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLinear range (\u0026micro;M)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLOD (\u0026micro;M)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eReference\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpectrophotometric analysis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.68\u0026ndash;66.76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColorimetric sensing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.2\u0026ndash;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHPLC \u0026ndash; ELSD\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67.9-679.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRP-HPLC\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.38-367.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDPV\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMIP/SPCE\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.5\u0026ndash;10.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSWV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHg(Ag)FE\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.42\u0026ndash;31.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMIP/ABP\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.10\u0026ndash;20.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDPV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFSCPE\u003csup\u003eg\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e44-1000\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSWV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePTCPE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.88-1\u0026times;10\u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eThis work\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003eHPLC \u0026ndash; ELSD: high performance liquid chromatography coupled with an evaporative light scattering detector; \u003csup\u003eb\u003c/sup\u003eRP-HPLC: reversed-phase- high performance liquid chromatography; \u003csup\u003ec\u003c/sup\u003eDPV: differential pulse voltammetry; \u003csup\u003ed\u003c/sup\u003eMIP/SPCE: molecularly imprinted polymer on a screen-printed carbon electrode; \u003csup\u003ee\u003c/sup\u003eHg(Ag)FE: silver-amalgam film electrode; \u003csup\u003ef\u003c/sup\u003eMIP/ABP: molecularly imprinted polymer/acetylene black-mod carbon paste; \u003csup\u003eg\u003c/sup\u003eFSCPE: fumed silica carbon paste electrode.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.8. Commercial samples study\u003c/h2\u003e \u003cp\u003eThe sensor\u0026rsquo;s feasibility was assessed by detecting AM in pharmaceutical samples using SWV, by spiking the samples with standard AM concentrations applying a standard addition method. Supplementary Table \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e displays the results, which confirm that the modified electrode can accurately measure AM in pharmaceutical samples with recoveries of 99.03\u0026ndash;103.22% and RSDs of 1.0% \u0026ndash; 3.4% for all samples. To evaluate the level of AM in the real samples, each measurement was performed with an average of five replicate trials.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003e3.9. PTCPE's long-term stability, repeatability, and interference study\u003c/h2\u003e \u003cp\u003eSupplementary Table S2 provides an illustration of how different interfering substances affect PTCPE's ability to detect AM. This was accomplished by loading equal and double amounts of several substances, such as urea, sucrose, glucose, starch, and paracetamol, into a fixed concentration of AM (600 \u0026micro;M). To confirm the selectivity of the suggested technique against AM, it was evaluated using the same experimental settings with other antibiotics and structurally related drugs such as erythromycin, clarithromycin, ciprofloxacin, cefixime, and cephalexin.\u003c/p\u003e \u003cp\u003eAs a recommended protocol for handling COVID-19 patients, paracetamol is commonly used with AM, so it is essential to examine the PTCPE\u0026rsquo;s selectivity for it. The sensor was competent for detecting both of them at distinct peak potentials of 0.36 V and 0.80 V for paracetamol and AM, respectively (Supplementary Fig. S3) without altering the sensor\u0026rsquo;s response to AM, demonstrating the sensor\u0026rsquo;s great selectivity.\u003c/p\u003e \u003cp\u003eFive sequent voltammetric determinations for 50 \u0026micro;M of AM with an RSD of 1.5% were performed to validate the reproducibility of PTCPE in terms of RSD, guaranteeing the precision of the electrode under investigation.\u003c/p\u003e \u003cp\u003eThe PTCPE was kept at room temperature for 12 days to examine its long-term stability. The sensor was then subjected to a single voltammetric measurement for AM, which revealed a current response of 97% of the value recorded right after fresh fabrication, indicating good electrode storage consistency.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eBased on the adjustment of CPE with PT, this work presented a sensitive and selective electrochemical sensor for identifying AM. To achieve the most sensitive determination of AM, a variety of electrochemical approaches were used to improve the experimental conditions. With a wide linear range of 8.88 \u0026ndash; 1000.0 \u0026micro;M of AM and a LOD of 0.32 \u0026micro;M, the newly manufactured sensor demonstrated its effectiveness in detection. The proposed approach was easy to use, inexpensive and sensitive enough to detect AM in medicinal capsules under physiological circumstances.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eAuthor contributions\u003c/p\u003e\n\u003cp\u003eS. Mamdouh:\u003c/p\u003e\n\u003cp\u003eDid the experimental work, converted the obtained data into various figures using SigmaPlot 10.0 and ChemDraw Professional 16.0, and suggested the electro-oxidation mechanism of the drug.\u003c/p\u003e\n\u003cp\u003eM. Shehata:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWrote the statistical analysis of the work, supplied the used chemicals, and helped in revising the manuscript.\u003c/p\u003e\n\u003cp\u003eA.M. Fekry:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInterpreted the data, demonstrated the EIS data, and wrote the SEM characterization.\u003c/p\u003e\n\u003cp\u003eM.A.Ameer\u003cstrong\u003e\u003cem\u003e(corresponding author)\u003c/em\u003e\u003c/strong\u003e:\u003c/p\u003e\n\u003cp\u003eInterpreted and reviewed all data\u003c/p\u003e\n\u003cp\u003eAll authors reviewed the manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eData availability statement\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003eCompeting Interests Statement\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eZuckerman, J.M. 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Chem\u003c/em\u003e. \u003cstrong\u003e41,\u003c/strong\u003e 11846\u0026ndash;11852 (2017). \u003c/li\u003e\n\u003cli\u003eFekry, A.M., Shehata, M., Azab, S.M. \u0026amp; Walcarius, A. Voltammetric detection of caffeine in pharmacological and beverages samples based on simple nano- Co (II, III) oxide modified carbon paste electrode in aqueous and micellar media. \u003cem\u003eSens. Actuators, B Chem\u003c/em\u003e. \u003cstrong\u003e302,\u003c/strong\u003e 127172 (2020). \u003c/li\u003e\n\u003cli\u003eZeng, A. et al. Determination of azithromycin in raw materials and pharmaceutical formulations by HPLC coupled with an evaporative light scattering detector. \u003cem\u003eAsian J. Pharm. Sci\u003c/em\u003e. \u003cstrong\u003e9,\u003c/strong\u003e 107\u0026ndash;116 (2014). \u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Scheme 1","content":"\u003cp\u003eScheme 1 is available in the Supplementary Files section.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"L-Threonine, COVID-19, Electropolymerization, Antiviral, Azithromycin","lastPublishedDoi":"10.21203/rs.3.rs-4737822/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4737822/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eA carbon paste electrode (CPE) was simply modified to detect AM using poly-threonine (PT). Azithromycin (AM) is one of the prescribed drugs in pandemic medication regimen which has a paying attention. The work was characterised using electrochemical impedance spectroscopy (EIS) and scanning electron microscopy (SEM). A very sensitive response to the oxidation of 1.0 mM AM in phosphate buffer solution (PBS) over a pH range of 5.0 to 10.0 was observed using a developed poly-threonine carbon paste electrode (PTCPE). In PBS with a pH of 7.4, the impact of different AM concentrations was investigated resulting in a detection limit of 0.32 \u0026micro;M and a quantification limit of 1.07 \u0026micro;M. Finally, the recently used electrode realized acceptable sensitivity and consistency for AM detection in pharmaceutical drugs.\u003c/p\u003e","manuscriptTitle":"Electro-polymerization of modified carbon paste sensor for detecting Azithromycin","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-13 13:07:13","doi":"10.21203/rs.3.rs-4737822/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-10-29T02:23:41+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-10T10:31:42+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313990797771831760202448203813906717849","date":"2024-10-05T09:08:49+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-07-24T11:00:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"125879081844026309047518730684296299586","date":"2024-07-24T06:24:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"188529858283204765204193210577836957630","date":"2024-07-24T01:26:32+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-23T19:44:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-23T19:43:24+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-07-23T18:11:54+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-19T10:59:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-07-14T09:28:51+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"017bb0cd-c859-4ac1-9a2d-67ee94d021b2","owner":[],"postedDate":"August 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":35991748,"name":"Earth and environmental sciences/Environmental sciences"},{"id":35991749,"name":"Physical sciences/Chemistry"}],"tags":[],"updatedAt":"2025-01-13T16:01:29+00:00","versionOfRecord":{"articleIdentity":"rs-4737822","link":"https://doi.org/10.1038/s41598-024-79614-6","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-01-06 15:56:53","publishedOnDateReadable":"January 6th, 2025"},"versionCreatedAt":"2024-08-13 13:07:13","video":"","vorDoi":"10.1038/s41598-024-79614-6","vorDoiUrl":"https://doi.org/10.1038/s41598-024-79614-6","workflowStages":[]},"version":"v1","identity":"rs-4737822","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4737822","identity":"rs-4737822","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}