Polymer free Nanocomposite from Zeolite and Carbon Black as Glassy Carbon modifier platform for Simultaneous Electrochemical Quantification of Acetaminophen and Caffeine

Polymer free Nanocomposite from Zeolite and Carbon Black as Glassy Carbon modifier platform for Simultaneous Electrochemical Quantification of Acetaminophen and Caffeine | 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 Research Article Polymer free Nanocomposite from Zeolite and Carbon Black as Glassy Carbon modifier platform for Simultaneous Electrochemical Quantification of Acetaminophen and Caffeine Firmin Parfait Tchoumi, Arnaud Kamdem Tamo, Giscard Doungmo, Cyrille Ghislain Fotsop, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3338753/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Mar, 2024 Read the published version in Journal of Applied Electrochemistry → Version 1 posted 13 You are reading this latest preprint version Abstract Nanocomposite nanozeolite/acetylene black carbon was prepared by combining a type A zeolite with acetylene carbon black (AcB) and used to modify glassy carbon electrode (GCE) without polymer. The zeolite was prepared by hydrothermal method using natural kaolin. The physicochemical characterization of the composite showed a well-integrated composite in which the cubic crystal of the zeolite A and the graphitic aggregate of the carbon black were maintained. The electrochemical impedance spectroscopy study revealed that the composite film GCE (ZA-AcB/GCE) prepared by drop coating displayed a higher kinetic charge transfer compared to pristine zeolite modified GCE (ZA/GCE) and bare GCE. ZA-AcB/GCE, ZA/GCE and GCE were subsequently used to investigate the electrochemical behaviour of acetaminophen (AC) in acidic, neutral and alkaline pHs. The results demonstrate a good electrocatalytic property toward AC at composite film GCE in all these electrolytes compared to bare GCE and confirm the dependence of the electrochemical reaction mechanism of AC on the electrolyte’s pHs. Under optimal conditions, ZA-AcB/GCE exhibited higher sensitivity and selectivity toward both analytes taken individually or simultaneously within large concentration range: 0.5–89 µM for AC and 5–99 µM for CAF with the respective limit of detection of 0.38 and 0.82 µM. The developed sensors were applied successfully in the quantification of the both analytes in pharmaceutical tablets. Acetaminophen Caffeine Zeolite-carbon composite Modified electrode Electroanalysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Introduction Acetaminophen or N-acetyl-p-aminophenol is a nonopioid non-NSAID (nonsteroidal anti-inflammatory drug) with analgesic and antipyretic action widely used to reduce fever and/or against mild to moderate pain associated to backache, headache, arthritis and postoperative pain[ 1 , 2 ]. Acetaminophen (AC) presents some side effects including the alteration of renal function and the inhibition of induction of labour[ 3 , 4 ]. In order to increase its efficiency without increasing the side effect, acetaminophen has been combined to opioids such as codeine, hydrocodone, and oxycodone. Unfortunately, this has led to an augmentation in the utilisation and misuse of opioids[ 5 ]. Moreover these combination induced some side effects with the long-time used[ 6 ]. Because of these limitations, a central nervous system stimulant: caffeine (CAF), has been used as adjuvant [ 7 , 8 ]. The presence of caffeine as adjuvant in paracetamol drug showed the enhancement and the prolonged analgesic activity of paracetamol and favoured its absorption[ 1 ]. It is therefore an increasing necessity to develop methods for the selective and sensitive detection and quantification of AC and/or CAF in biological fluid as well as in pharmaceutical formulations. Thus, for this purpose several successful methods have been developed including chromatography and UV-spectrophotometry [ 9 , 10 ], despite the fact they are costly and may require sample pre-treatment and long time. Alongside of these methods, electrochemical methods have immerged a cheap, simple, rapid, sensitive and accurate for the determination of AC and CAF. However the use of classical electrodes was limited by high positive oxidation potential of caffeine, electrode fouling by the product of the oxidation of acetaminophen and low reproducible analysis [ 11 – 13 ]. In order to overcome these drawbacks and improve the electrochemical sensitivity and selectivity, modified solid electrode substrate using different type of materials have been developed. Among the modifiers, zeolites occupy a prominent place because of their interesting physicochemical properties [ 14 ]. Zeolite modified electrodes have attacked the attention of researchers in recent years as evidenced by considerable progresses observed in this field [ 15 , 16 ]. Conventional zeolites which generally exists as fine powder made of crystals of microscopic size are easily incorporated in carbon paste to obtained carbon paste electrodes. Despite the insulating character of the zeolite, zeolite modified film electrodes have been reported in the literature and required the use of a binder (generally polymer) acting as sticker of zeolite particle together and favoured a thin layer on the electrode substrate [ 17 ]. Although the resulting polymer zeolite film electrodes were successfully applied, they are poorly mechanical stable and generally irreproducible, as reported by Shaw et al [ 18 ]. These limitations have been overcome by using nanozeolite or metal doped zeolite, but still required polymers to form a stable film electrode on various conductive substrate. In addition, the metal precursors used to prepare zeolites modified electrode are of a high cost, a limited availability, low selectivity, poor durability and often not respectful of the environment, [ 19 ]. In the present work an eco-friendly nanocomposite was prepared by mixing high surface area nanozeolite A with acetylene carbon black. The as-synthesised nanocomposite was used to form by drop coating onto GCE’s surface, a stable thin film without any binder. Taking advantage of excellent electrical conductivity offered by acetylene carbon black [ 20 , 21 ] and large specific surface area nanosize zeolite, the composite modified electrodes were successfully applied in the individual and simultaneous quantification of AC and CAF in aqueous milieu. The developed sensors were successfully used for the simultaneously quantification of the both analytes in drugs formulations. Experimental Section 1.1. Materials and chemicals The nanozeolite type A denoted “ZA” used as one composite constituent was synthesised as described in our previous work using beneficiated rich quartz kaolin as silicon and aluminium sources [ 22 ]. Acetylene carbon black (AcB), K 3 Fe(CN) 6 (> 99%), phosphoric acid (H 3 PO 4 , 85%) and N,N dimethylformamide (DMF, 99.8%) were purchased from Abcr. Caffeine (C 8 N 4 O 2 H 10 , anhydrous powder 99%), acetaminophen (95%), potassium chloride (KCl, 99%), acetic acid (CH 3 COOH, 99%), boric acid (H 3 BO 3, 99.99% ) and NaOH (97%) were from STREM chemical. The Britton–Robinson buffer (BRB) solution in the pH range from 2 to 9 was prepared by mixing H 3 BO 3 , H 3 PO 4 and CH 3 COOH in deionized water. The desired pH was obtained by adjusting the pH solution with 0.2 M NaOH. 1.2. Preparation of acetylene carbon black-zeolite composite The composite ZA-AcB was prepared by the combination of AcB with ZA. Firstly, a homogenous ZA’s suspension (2g/L) was prepared by dispersing ZA in dimethylformamide. To this suspension a given amount of AcB (2.5, 5, 10, 20 and 30%wt) was then added to ZA’s suspension under vigorous stirring. This mixture was sonicated for 30 min and then kept under stirring for 24 hours. 1.3. Instruments X-ray diffraction analysis was performed using a STOE Stadi-p X-ray powder diffractometer (Stoe & Cie GmbH, Darmstadt, Germany), with Cu Kα1 radiation (40 kV, 30 mA, and λCu = 1.54056 Å). The material’s morphology was obtained with scanning electron microscope (Amray 1610 Turbo, Anray Inc., Bedford, MA, USA) at an accelerating voltage of 15 kV. The EDX mapping was performed on Fiel-emission scanning electron microscopy equipped with energy-dispersive X-ray (EDX) spectroscopy. The surface area and porosity were determined by nitrogen adsorption–desorption isotherms recorded at 77K using a Micromeritics analyser (Termo Electron Corporation, Germany). The thermal gravimetric analysis (TGA) was performed on TA Instruments TGA, Netzsch under nitrogen atmosphere, with a heating rate of 10 ᵒ C.min − 1 . Electrochemical measurements were conducted on Corrtest Electrochemical Workstation and µ-Autolabpotentiostat/galvanostat equipped with CS Studio 5 and GPES (General Purpose Electrochemical System) respectively, in a conventional three electrodes cell with a saturated calomel electrode as reference electrode, a platinum wire as counter electrode and either bare or modified glassy carbon as working electrode. Genesys 10S Thermo Scientific spectrophotometer was used to collect UV-vis spectra. 1.4. Preparation of the working electrodes A glassy carbon electrode (GCE) was used as working electrode substrate. Prior its use, GCE was polished on a mirror-like surface with aqueous alumina slurry of three grain sizes (1, 0.3 and 0.05 µm) on individual wet polishing cloth, followed by thorough rinsing with distilled water. After that, the electrode was sonically cleaned in 1:1 water-ethanol for 20 minutes to remove any traces of alumina. ZA and ZA-AcB film working electrodes were prepared by drop coating a given volume of either ZA-AcB or ZA suspension (2 g/L) onto GCE surface, and the coating was allowed to dry at room temperature for one hour and rinsed with distilled water before use. The resulting electrodes are denoted ZA/GCE when the zeolite suspension was used and ZA-AcB/GCE when the composite suspension was dropped. 1.5. Real sample preparation Three commercial brands tablets containing AC and CAF namely Panadol (500 mg of paracetamol and 65 mg of caffeine), Ibex (325 mg paracetamol and 30 mg caffeine) and Dolimex (500 mg of paracetamol and 50 mg of caffeine) purchased in local pharmacy were used as real samples. The real sample’s solution was prepared by dissolving fine powdered tablet in distilled water. Then x microliter of the dissolved drug was then transferred into 10 mL volumetric flask and dissolved with BRB (pH 3). For UV analysis, the preparation of the real sample analyte follows the same procedure as described above. Results and discussion 2.1. Physicochemical characterisation of zeolite-carbon composite The XRD pattern of ZA-AcB composite (spectrum a in Fig. 1 A) shows 2θ peaks (7.24°, 10.2°, 12.5°, 16.2°, 20.4°, 21.64°, 23.97°, 26.14°, 27.32°, 31.03°, 32.72°, 33.43° and 34.2° ) well aligned on those of characteristic peaks of zeolite type A (spectrum c in Fig. 1 A) reported in our previous work[ 22 ], the first four peaks being increased slightly. In addition, two broad peaks clearly observed at 2θ equal to 25.77° and 43.21° on spectrum b attributed to the hexagonal graphitic structure of the carbon black [ 23 ], are absent on pattern of pristine zeolite and that of the composite. These results suggest that ZA has likely embedded the amorphous carbon without loss of their respective structural integrity as reported in the literature [ 24 , 25 ] and AcB being located in the zeolite interparticle spaces. The average crystallite size of the composite was estimated using Sherrer’s equation utilising XRD data and was found to be ca 59.62 nm, close to the average crystallite size of the pristine zeolite reported in our previous work [ 22 ]. The FTIR spectrum of ZA-AcB (Fig. 1 B, plot a) exhibited zeolite type A’s characteristic bands as do pristine ZA [ 22 ] (Fig. 1 B, plot c) in addition to characteristic bands of chemical function of acetylene black (at 1550, 1150 and 1050 cm − 1 corresponding to C = C, C-OH and C-O-C, respectively[ 26 , 27 ].) as shown in Fig. 1 B (plot b). Interestingly, two bands at 2922 and 2850 cm − 1 attributed to –C-H- bond [ 27 ] absent on the spectra of ZA and ACB were observed on the spectrum of the composite. The surface morphology of the composite and pristine zeolite was investigated by scanning electronic microscopy (SEM). Figure 1 C and D present respectively, the SEM images of pristine zeolite and zeolite acetylene carbon black composite. In Fig. 1 D, one can observe clearly a well-defined cubic shape characteristic of zeolite type A (similar with that observed on the image of pristine zeolite in Fig. 1 C) with uniformly distributed aggregate of carbon black particles. These observations indicate that the zeolite shape was not affected by the presence of carbon. The elemental mapping of ZA-AcB (Fig. 1 E) shows a homogeneous distribution of AcB within the composite highlighted by the green colour corresponding to carbon (E-1), the red colour to oxygen (E-2), bleue cyan to sodium (E-3), bleue to aluminium (E-4) and orange to silicium (E-5). EDX analysis results exhibited in Fig. 1 F confirms that the composite was made of oxygen (27%), silicon (25%), aluminium (23%), sodium (15%) and carbon (10%). The BET surface area and pore volume of the composite were found to be 27.98 m 2 /g and 0.037 cm 3 /g; respectively. The results are ca 50% of those of pristine zeolite reported previously [ 22 ], likely because AC has blocked or/and filled some zeolite micropore by creating a heterogeneous environment within the composite [ 24 ]. Figure S1 presents the thermal gravimetry analysis of the composite (curve a) and the pristine zeolite (curve b). Both materials present two main weight loss changes, the first at temperature range 60°C − 200°C and the second at 200°C – 400°C related respectively, to the loss of adsorbed water and water forming the hydration complexes with cations located in the cages of the zeolite[ 28 ]. It is worth noted that ZA-AcB displayed a weight first loss of ca 13% and the second loss of ca 2% lower than 17% and 4% obtained for pristine ZA. This behavior is attributed to the decreases of the composite’s micropore volume created by its heterogeneous structure leading to the decreases in moisture loss [ 24 ]. 2.2. Electrochemical characterisation of ZA-AcB/GCE The ability of the pristine zeolite and the composite to form a stable film onto glassy carbon electrode has been tested using cyclic voltammetry (CV) in diluted solution of [Fe(CN)6] 3− as redox probe. Figure 2 shows the multistep voltammetry recorded at modified and unmodified electrodes at 50 mV.s − 1 . As expected, at pristine zeolite modified GCE (namely ZA/GCE), CVs recorded shows poorly defined redox peak of [Fe(CN) 6 ] 3− which is due to the electrostatic repulsion between negatively charged ZA film and the anionic probe. Thus, ZA film onto GCE acts as barrier vis-a-vis of redox probe, preventing the diffusion of [Fe(CN)6] 3− to the glassy carbon electrode. In contrast, when GCE was coated with the composite film, a simultaneous growth of cathodic and anodic peaks was observed upon repetitive scan potential and reached a steady state after 30 cycles, indicating the accumulation of the negative probe within the composite film. Moreover, the maximum steady state exhibited peak to peak potential separation ∆E = 100 mV and peak current ratio Ipc/Ipa ≈ 1; illustrating a quasi-reversible process. Interestingly the maximum steady state current recorded at ZA-AcB/GCE was four time higher that that obtained at bare GCE. All these results clearly demonstrated: (i) the stability of the composite film and its pre-concentration capability of the negative probe despite the presence of the negatively charged zeolite within the film and (ii) the presence of AcB within the film thanks to its electronic conductivity and its pore, which favoured the diffusion of the probe to the GCE. The electron transfer property of the modified electrodes was studied using electrochemical impedance spectroscopy (ESI). The Nyquist plots of EIS recorded in 0.1 M KCl solution containing 0.5 mM of [Fe(CN) 6 ] 3−/4− ions are shown in Fig. 2 E. The Nyquist plot recorded at ZA/GCE (curve a), exhibited the largest semi-circle i.e largest charge transfer resistance (Rtc = 9.1 kΩ) compared with those recorded at bare GCE (Rtc = 3 kΩ) and at ZA-AcB/GCE (Rtc = 1.5 kΩ), indicating that the electron transfer rate is faster at composite modified electrode. These results are in accordance with CV result. The effective surface area of the modified electrode was evaluated by applying the Randles Sevcik equation (Eq. 1) using data obtained from the study of the effect of the scan rate on the electrochemical response recorded in [Fe(CN) 6 ] 3− at ZA-AcB/GCE as shown in Fig. S3: Ip = 2.69×10 5 × (D 0 ) 1/2 ·A·v 1/2 ·n 3/2 ·C 0 (Eq. 1) Here, for [Fe(CN) 6 ] 3− /[Fe(CN) 6 ] 4− , n = 1, C 0 = 5.10 − 7 mol.cm − 3 , D 0 = 7.6×10 − 6 cm 2 .s − 1 [ 29 ]. From the slope obtained by plotting Ipa vs. v 1/2 (inset Fig.S3C), the effective surface area of ZA-AcB/GCE was estimated to be 0.0035 cm 2 , which is 3 time that of bare GCE. Application of the composite modified electrode to the electroanalysis of acetaminophen and caffeine The electrochemical behavior of AC and CAF was study at modified electrode ZA/GCE and ZA-AcB/GCE. Because AC’s electrochemical oxidation is known to very often parallel some catalyzed oxidation in the organism[ 30 ], thus it was very important to study its oxidation which strongly depends on the solution’s pH [ 30 ]. 3.1. Electrochemical behaviour of acetaminophen at ZA-AcB/GCE The electrochemical oxidation of AC was study in various pHs (3.0, 7.0 and 11.8) utilizing cyclic voltammetry. Figure 3 shows the cyclic voltammograms recorded at bare GCE (curve a), ZA/GCE (curve b) and ZA-AcB/GCE (curve c) in various pH’s solution containing AC. One can observe that when the potential is scanned in the positive direction, the CVs recorded at modified and unmodified electrodes exhibited one main well defined oxidation peak with potential peak shifting as expected to positive potential when decreasing the solution’s pH. This observation indicates the participation of protons(s) in AC oxidation to N-acetyl-p-benzoquinone-imine (NAPQI) (see scheme 1 ). Interestingly, in the reverse scan potential in acidic solution (pH 3.0) two reduction peak C1 and C2 were observed on CVs a), b) and c); C1 ill-defined corresponding to the reactivity of the electrochemical generated NAPQI[ 30 ] and C2 to the reduction of P-benzoquinone, P-benzoquinone being the product of successive chemical reactions in acidic condition of NAPQI (scheme 1 A). The dome (A2) observed in this CV (a) at ca + 0.23 V in the positive potential scan may be the oxidation of the product of the p-benzoquinone electrochemical reduction. Moreover, it is worth noting that the current peaks corresponding to the oxidation of AC (A1) and to the reduction of p-benzoquinone (C2) recorded at ZA/GCE are greater than those recorded at bare GCE. This can be explained by the fact that in acidic media, AC (pKa 9.5) as well as NAPQI are positively charged, thus there will be a favorable electrostatic interaction between these products facilitating its detection at GCE. Indeed, since AC is essentially size excluded from zeolite A aperture (4Å) [ 31 ], its cationic form is therefore more likely trapped on the external surface of the zeolite, thus improving its electrochemical reaction at zeolite-electrode-solution interface. This suggest an extrazeolitic mechanism of AC at ZA/GCE via ion exchange properties. Interestingly at ZA-AcB/GCE (Fig. 3 A-c), the anodic peak current recorded is 1.5 time greater than that obtained at ZA-GCE. Thus, compared to GCE and ZA/GCE, there is a gain in potentials and current intensities at ZA-AcB/GCE, highlighting the good electrocatalytic activity of the composite modified electrode owing to the synergic effect of the nanoscale zeolite and high electron conductive carbon black. In phosphate buffer (pH 7.0), the CVs recorded at modified and unmodified GCE show one well defined oxidation peak when potential was scanned at either 10mVs − 1 (Fig. 3 B) or 100 mVs − 1 (dashed plots inset Fig. 3 B) in positively direction and one cathodic peak in the reversed potential scan. This quasi-reversible process corresponds to two electron electrochemical redox reaction of AC to NAQPI[ 30 ]. In addition, for all the three voltammograms of Fig. 3 B, the current ratio Ip C1 /Ip A1 was found to be 0.15 at GCE, 0.44 at ZA/GCE and 0.65 at ZA-AcB/GCE, suggesting that part of NAPQI is likely involved in the chemical reaction leading to the formation of dimer (see scheme 1 B). Interestingly one can note that the CV recorded at ZA-AcB/GCE at for example 10 mVs − 1 exhibited the separation peak to peak potential ∆E was about 0.26 V about half that of those obtained at CV (a) and (b). Moreover, both the cathodic and anodic peak currents at CV (c) significantly increased compared with those recorded at ZA/GCE and bare GCE. All these results indicate that although the reaction mechanism of AC is the same at modified and unmodified electrodes, the presence of carbon black within the composite onto the electrode surface has favored the oxidation of AC to NAQPI and vice-versa, thus highlighting electrocatalytic of composite modified electrode toward the AC in this media. Figure 3 C and D presents, respectively the CVs recorded in alkaline media (pH 11.8) containing AC at modified and unmodified electrodes at 100 mVs − 1 and at 10 mVs − 1 . One can observed that the CVs recorded at unmodified GCE (curve a)) by scanning the potential at 100 mV s − 1 exhibits mainly a well-defined anodic peak A1 at + 0.30 V attributed to the oxidation of AC (1) to NAPQI (2) and two cathodic peak C1 and C2 at + 0.13 V and − 0.15 V respectively. The ill-defined peak C1 corresponds to the reduction of NAPQI (2) to AC[ 30 ] and C2 to the reduction of O -benzoquinone (3) to N-(3,4-dihydroxyphenyl) acetamide (3-hydroxyacetaminophen) (4) [ 30 ]which oxidation (A2) is observed as a hump at − 0.04 V. At modified GCEs, the recorded CVs (curves b and c) are quite similar and exhibit an oxidation peak A1 and a reduction peak C1 as observed on CV (a) recorded at bare GCE and one reduction peak located respectively, at -0.19 V at ZA/GCE and at -0.13 V at ZA-AcB/GCE. These reduction peaks may be composite of C1 and C2 observed on CV (a). Interestingly, when the potential was scanned at low scan rate (< 50 mV.s − 1 ) with ZA-AcB/GCE and ZA/GCE, the reduction peak splitted in two reduction peaks namely C2 and C3 appearing, respectively at − 0.15 V and − 0.26 V (CV b) and c) in Fig. 3 D), the oxidation peak being unchanged in term of potential. The peak C3 at − 0.26 V was likely attributed to the reduction of P -benzoquinone (6) to N-(2,4,5- trihydroxyphenyl)acetamide (5) (reaction III), N-(2,4,5- trihydroxyphenyl)acetamide being obtained from (4) via the Micheal addition of hydroxide ion [ 30 ]. Thus, by lowering the potential scan rate, the product of reaction III may quantitatively present at the electrode interface and then led to the appearance of peak C3 (see Fig S3) corresponding to the reduction of compound (6) to compound (5). In addition, in the second potential scan (solid lines), a new anodic peak A3 appears at − 0.15 V, corresponding to the oxidation of (5). At bare GCE, the decrease in potential scan rate did not lead to any change in CV shape (CVs a) in Fig. 3 D). This behavior is a clear evidence of the good electrocatalytic properties of the composite modified electrode toward the electrochemical analysis of AC. From the above study it appeared that in acid, neutral and alkaline media, the oxidation of AC to NAPQI was well defined with peak potential dependent of solution pHs. In order to avoid the effects related to the concentration of the analyte and to preserve the authenticity of the reactions taking place, the electroanalysis of AC was carried out in buffer medium. Robinson buffer solution (RB) offers a large range of pH ranging from 2 to 12, thus it was used to perform the next steps of this work. Prior to this, CVs recorded at ZA-AcB/GCE in RB containing AC were compared with those recorded in electrolyte solution pH 3 (Fig. SA), (Fig. S4B) and 11.8 (Fig. S4C) containing the same amount of AC. It is clearly observed that all the recorded CV at ZA-AcB/GCE exhibited the same shape with peak current as well as peak potential quite the same, indicating that the electrochemical signature of AC at quite identical in both media. From all these findings, it appears that the electroanalysis of AC at modified electrodes can be monitored by studying the main oxidation peak due to the electrochemical transformation of AC to NAQPI. 3.2. Electrochemical behaviour of AC in presence of CAF at ZA-AcB/GCE As reported in the literature, the electrochemical behaviour of CAF is well highlighted in acidic media [ 32 ], thus the electrochemical behaviour of AC in the presence of CAF was studied in RB pH 3.0. Figure 4 shows CVs recorded in 0.04 M RB (pH 3.0) containing a mixture AC (98 µM) and CAF (202.8 µM) at bare GCE (curve a), ZA/GCE (curve b) and ZA-AcB/GCE (curve c). It can be observed at modified and unmodified electrodes, the forward potential scan in the positive direction led to two oxidation peaks: the first at less positive potential corresponding to the oxidation of acetaminophen and the second at more positive potential to the oxidation of caffeine. On the reverse scan, one low and ill-defined reduction peak was observed on CVs recorded at bare GCE and ZA/GCE ( ~ + 0.46 V) which corresponds to the reduction of NAPQI to AC as reported in section 3.1. Interestingly, at ZA-AcB/GCE, the recorded CV(curve c) displays a well-defined quasi-reversible process with redox peak centered at + 0.49 V with ΔE = 0.60 V (current ratio Ipc (3.5 µA)/Ipa (5.25 µA) equal to 0.7) while CAF undergoes an irreversible oxidation peak current at + 1.35 V. Furthermore, the oxidation peak potential of AC and CAF obtained on composite modified electrode are negatively shifted respectively for 38 mV and 32 mV of those recorded at bare GCE; and 53 mV and 40 mV of those recorded at ZA/GCE. Furthermore, the oxidation peaks current of AC and CAF recorded at ZA-AcB/GCE were respectively about 3.5 and 2 times greater than those obtained with bare GCE, 5 and 2.8 time greater than those recorded with ZA/GCE. Thus, the increase in peak current associated with the lowering potential demonstrated that the combination of nanozeolite with carbon black as an electrode modifier has an electrocatalytic activity towards the oxidation of both AC and CAF. This result is likely due on one hand to the favourable electrostatic interaction between cationic form of analytes and the negative charged of the nanoscale zeolite particles and on the second hand to the good electron conductor of AcB. 3.3. Effect of scan rate The relationship between the scan rate and voltammetric response gives informations about the nature of the electrochemical process occurring at nanocomposite modified electrode. Figure 5 A and 5 B shows the CVs recorded at different scan rates in RB pH 3 containing a mixture of AC and CAF, respectively. From the CVs in shown in Fig. 5 , one can note that the oxidation and reduction peak current increased as the scan rate increases for the both analytes and the plots of peak current versus square root of the scan rate resulted in a straight line (R² = 0.998 for both analytes, inset Fig. 5 ). The obtained linearity suggests that the electrochemical process governing the charge transfer is the diffusion of analytes. Additionally, the slope of log of peak current versus log of scan rate is 0.42 for CAF (line a in Fig. 5 C) and 0.38 and 0.50 for AC (lines b and c, Fig. 5 C) respectively. These values are close to the theoretical value 0.50 expected for diffusion-controlled electrode process [ 33 , 34 ]. This confirms that the electrochemical oxidation of these analytes was predominantly governed by an apparent diffusion process. 3.4. Effect of pH In order to determine the optimal pH and confirm the involvement of proton in the electrochemical reaction, the effect of the buffer’s pH on the sensitivity of ZA-AcB/GCE towards both analytes was investigated in RB’s pH ranging from 2 to 9 containing the mixture of analytes (225.5 µM CAF and 99 µM AC). Figure 6 A presents the CVs recorded at ZA-AcB/GCE. As can be observed the cathodic and anodic peak potential shifted positively with pH increase. As shown in Fig. 6 B, the plots of I pa versus pH indicate that the oxidation peak current is affected by electrolytic solution’s pH (Fig. 6 B curve a for AC and curve b for CAF), the higher peak current being obtained at pH 3. Therefore, pH 3 was chosen for the electroanalytical experiments of the both analytes. In addition, the plots of E 1/2 and Ep a versus pH result in a linear regression (Fig. 6 B) as presented by plot c for AC and plot d for CAF, respectively. The corresponding linear equations are as follows: E 1/2,AC = -0.053 pH + 0.68 (R²= 0.974) (Eq. 2) E p,CAF = -0.015 pH + 1.42 (R²= 0.970) (Eq. 3) The value of slope of Eq. 2, 53 mV/pH obtained for AC is close to the theoretical value 59 mV/pH corresponding to the involvement of equal number of electron and proton, thus for two electrons involved in the electrochemical reaction of AC, they are accompanied by two protons (scheme 1 A). For CAF, the slope of Eq. 3 is 15 mV/pH as reported elsewhere[ 35 – 37 ], suggesting there is not an equal number of proton and electrons involved in the oxidation of CAF in opposition to CAF’s electrochemical reaction exhibited in scheme 1 B. Even if the reason of the behaviour is not yet well known, it appeared that the electrooxidation of CAF at ZA-AcB/GCE is more complex. 3.5 Effect the amount of acetylene carbon black and the film thickness . The influence of the amount of AcB within the film composite onto GCE on the sensitivity of the composite modified GCE towards AC and CAF was investigated using DPV by varying the amount of AcB from 0 to 30 wt% used in the preparation of the composite. From this graph, on can observed that the electrochemical response of the oxidation of AC and CAF varied when different ZA-AcB/GCE prepared using composite with different AcB content were used to record the response in the same solution ( RB pH3 containing fix concentration of AC and CAF). The results are presented in Figure S5-A (curve a for AC and curve b for CAF). They show that the oxidation peak current of the both compounds increased with AcB content in the composite film GCE and the maximum current was obtained when the composite film was made with a composite containing 10% of AcB then levelled off. This can be explained by the fact that the high content of AcB may lead to less stable film due to its hydrophobicity. Thus, the film was further prepared using composite made of 10% of AcB. The effect of suspension’s volume allowed to dry on the sensitivity of the composite film electrode was investigated in the range of 1.5µL-7.5µL of the 10% AcB /ZA suspension. Figure S5-B depicts the effect of anodic peaks current (for AC (curve a) and CAF (curve b)) versus volume of the suspension’s volume. As can be seen, the oxidation current peak of the both analytes increased with the volume of the suspension of ZA/AcB and reached the maximum for 5µL of the suspension and then decreased for higher volume. The slight decrease of the electrochemical response could be the result of the larger film thickness which becomes not only unstable but also resistant to the diffusion of analytes onto the surface of the electrodes. 3.6. Individual and simultaneous determination of AC and CAF Figure 7 A shows the DPVs recorded at ZA-AcB/GCE in RB pH 3 in which successive addition of either AC or CAF were added. One can observe that the electrochemical oxidation current in each case increased when the concentration of the analyte was increased. It was observed that the oxidation peak current was linearly dependent on the concentration of AC ranging from 0.5 to 89 µM (see inset Fig. 7 A) and from 5 to 99 µM (see inset Fig. 7 B) for the CAF with regression equations: Ip = 0.052 [AC] + 0.010 (R² = 0.994) (Eq. 4) Ip = 0.040 [CAF] − 0.236 (R² = 0.999) (Eq. 5) Interestingly when successive additions of AC were made into the electrolyte containing fix concentration of CAF (89 µM), the oxidative peak current of AC increased synchronously while the CAF’s oxidation current remained constant (see Fig. 7 C). Similar behaviour was observed when increasing concentration of CAF was added to the electrolytic solution containing fix concentration of AC (87.6 µM) (see Fig. 7 D). These increases are linearly depended on the concentration of each added analyte with regression equations: Ip = 0.057 [AC] – 0.846 (R²= 0.994) (Eq. 6) Ip = 0.443 [CAF] – 0.330 (R²= 0.997) (Eq. 7) It is worth noted that the sensitivities of ZA-AcB/GCE obtained for individual addition of each analyte and for addition of one analyte in presence of each other was found to be quite close. These results demonstrate that the prepared sensors are a promising candidate for individual and simultaneous detection of AC and CAF without any interference. The detection limit based on S/N = 3 was estimated to be 0.38 µM and 0.82 µM for AC and CAF respectively. Further, the simultaneous addition of AC and CAF in RB pH 3 has led to two well resolved independent oxidation peak at + 0.51 V for the electro oxidation of AC and + 1.36 V electro-oxidation for CAF as shown in Fig. 7 E. The peak current increased with continuous addition of the both analytes and the peak current were linearly depended on the concentration of each analyte from 11 to 80 µM for AC (R²= 0.997) and 20 to 134 µM for CAF (R²= 0.994) with sensitivity of 0.056 µA/µM and 0.051 µA/µM for AC and CAF, respectively. Thus, the oxidation peak potentials of the obtained DPVs as well as their sensitivities match well with those obtained with individual analyte. The comparison of the performances of ZA-AcB/GCE and other electrodes reported for determination of acetaminophen and caffeine described in the literature are listed in Table 1 . It is clearly noted that the developed sensors have appreciable linear range with a detection limit of the same order of magnitude and even lower than some of previously reported works. Table 1 The comparison of the analytical performances of ZA-AcB/GCE for caffeine and paracetamol determination with previously reported electrodes. Electrodes Method Analytes Linear range (µM) Detection limit (µM) References Nafion®HNT/GCE 1 DPV AC 0.6–14 0.011 [ 33 ] CAF 0.6–20 0.173 poly(AHNSA)/GCE 2 SWV AC 10–125 0.45 [ 38 ] CAF 10–125 0.79 aGCE 3 SWV AC 10–180 2.55 [ 39 ] CAF 10–95 2.36 Lt/fMWCNT/MGCE 4 DPV AC 0.9–80 0.78 [ 2 ] CAF 10–110 3.54 CS-Fe 3 O 4 NP/GCE 5 DPV AC 50-2000 16 [ 40 ] CAF 50–900 23 GC-SnS/TiO 2 -GO 6 DPV AC 0.009-280 7.5 [ 41 ] CAF 0.0166-333 4.4 MOF-199/Naf-GCE 7 DPV AC 0.1–5 1.3 [ 36 ] CAF 0.2–5 1.2 PT/TiO 2 -Gr/GCE 8 DPV AC 0.1–90 0.034 [ 42 ] CAF 0.25–200 0.5 ZA-AcB/GCE DPV AC 0.5–89 0.38 This work CAF 5–99 0.82 1 Nafion halloysite nanotube modified glassy carbon electrode; 2 Poly(4-amino-3-hydroxynaphthalene sulfonic acid)-modified glassy carbon electrode; 3 activated glassy carbon electrode; 4 Luteolin on functionalized multi-wall carbon nanotube modified glassy carbone electrode ; 5 cassava starch-Fe 3 O 4 nanoparticles modified glassy carbone electrode; 6 Tin sulphite (SnS) and titanium dioxide (TiO 2 ) on grapheme oxide (GO) sheets modified glassy carbon electrode; 7 metal organic framework-199/nafion modified glassy carbon electrode; 8 Poly(taurine)/TiO 2 graphene composite modified glassy carbon electrode 3.7. Reproducibility, stability and Interferences study of ZA-AcB/GCE The reproducibility of ZA-AcB/GCE was evaluated by carrying out repetitive measurement-regeneration cycles. The results of the respective measurements recorded in RB (pH 3.0) containing 240 µM of CAF and 85 µM of AC are presented in Fig. 8 . The DPVs obtained display a relative standard deviation of 6.5% and 4.6% for AC and CAF respectively. This suggests that the prepared sensor exhibited a good reproducibility performance toward the simultaneous detection of these compounds. The results obtained in Fig. 7 above confirm the good operational stability of the composite modified glassy carbon electrode. The developed sensors have proven 95% of repeatability after one week of use. The interference effects of potentially interfering substances on the DPV response of AC and CAF at ZA-AcB/GCE were evaluated. Figure S6 shows DPVs of AC and CAF simultaneously introduces gradually from 2–22 µM and 20–220 µM respectively, in RB (pH 3) containing 280 µM of ascorbic acid (AA), glucose (Glu) and tyrosine (Tyr). It is clearly observed that current peak due to the oxidation of AC and CAF increased as their concentration increased. This result shows that none of the foreign molecules significantly interfered with AC and CAF (signals change below 5%) except UA (> 50 µM) was found to interfere with AC. This confirms the good selectivity of ZA-AcB/GCE in complex solution toward simultaneous detection of AC and CAF. 3.8. Simultaneous quantification of AC and CAF in pharmaceuticals formulations The developed sensors were also applied for the quantification of AC and CAF in tablets containing the both analytes using standard addition method. Each analyte was analysed by introducing a known amount of tablet sample analytes in voltametric cell and the corresponding DPVs recorded. This was followed by 3 successive simultaneous additions of AC and CAF standard solution and the resulting DPVs (added real sample: dashed line and standard solution: solid line) are presented in figure S7-A, S7-B and S7-C for Panadol , Ibex and Dolimex tablet’s brand, respectively. It is clearly observed from these CVs that simultaneous addition of AC and CAF standard solution led to an increase of current peak. From the slopes of the regression lines (shown in inset Fig. S7) obtained by plotting current intensities versus the added amount of AC and CAF versus the electrochemical oxidation’s response, the amounts of both analyte in tablets were determined and their subsequent recovery percentage were estimated to range between 94–101% and 93–100% for AC and CAF respectively (see Table 2 ). These results demonstrate that the potential applicability of ZA-AcB/GCE for the determination of AC and CAF in drug samples without any interference, which is not the case when using UV spectrophotometer because AC and CAF were found to interfere (see Fig. S8). Table 2 Determination of AC and CAF quantities in tablets using the ZA-AcB/GCE Tablets brand Added (µM) Founded (µM) a % recovery ± %RSD AC CAF AC CAF AC CAF PANADOL 70 7.2 68.84 6.78 97.91 ± 1.03 93.88 ± 5.62 IBEX 244 17.2 245.85 16.60 100.76 ± 1.52 96.55 ± 1.25 DOLIMEX 512 27 483.27 26.82 94.31 ± 2.52 99.36 ± 1.95 a average of three replicate measurements CONCLUSION In this work a nanocomposite was successfully prepared by mixing a type A nanozeolite with acetylene carbon black. The physicochemical characterization of the composite shows a good interaction between both materials in which their structural integrity was maintained. The sensors prepared by coating composite film onto glassy carbon surface were found to be stable and exhibited high charge transfer kinetic and electrocatalytic toward AC thank to the synergic effect of the structural properties of nanozeolite and the electron conductivity of the carbon black. The developed sensors were successfully used to monitor the reactivity of acetaminophen and caffeine with good sensibility. Under optimum conditions, these sensors displayed large calibration curve for acetaminophen and caffeine with low detection limits. They were then successfully applied to the quantification of AC and CAF in drugs. Declarations Conflict of Interest There is no conflict to declare Acknowledgment Financial support from the Royal Society ACBI programme (Grant AQ150029) is gratefully acknowledged References Renner B, Clarke G, Grattan T, Beisel A, Mueller C, Werner U, et al. Caffeine accelerates absorption and enhances the analgesic effect of acetaminophen. 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\u003cstrong\u003eB\u003c/strong\u003e) FTIR of a) ZA-ACB, b) ACB, c) ZA; \u003cstrong\u003eC)\u003c/strong\u003e and \u003cstrong\u003eD)\u003c/strong\u003e SEM images of ZA and ZA-ACB respectively; \u003cstrong\u003eE\u003c/strong\u003e) EDX-mapping and element distribution mapping of C, O, Na, Al and Si (from E-1 to E-5 respectively) of ZA-ACB. \u003cstrong\u003eF\u003c/strong\u003e) EDX spectrum of ZA-ACB composite\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/d3728121c5de3ca672840f27.png"},{"id":43147750,"identity":"f8c0afde-d960-4a87-a6c6-55bd0f87f4bd","added_by":"auto","created_at":"2023-09-14 17:21:31","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":35956,"visible":true,"origin":"","legend":"\u003cp\u003eMultisweep cyclic voltammograms recorded at: \u003cstrong\u003eA)\u003c/strong\u003e Bare GCE, \u003cstrong\u003eB)\u003c/strong\u003e ZA-GCE and \u003cstrong\u003eC\u003c/strong\u003e) ZA-ACB/GCE in 0.1 M KCl containing 0.5 mM Fe(CN)\u003csub\u003e6\u003c/sub\u003e\u003csup\u003e3− \u003c/sup\u003eat scan rate: 50 mV.s\u003csup\u003e-1\u003c/sup\u003e; \u003cstrong\u003eD\u003c/strong\u003e) Superposition of cyclic voltammograms at equilibrium. \u003cstrong\u003eE)\u003c/strong\u003e Nyquist plots recorded onto a) ZA/GCE, b) bare GCE and c) ZA-ACB/GCE in 0.1 M KCl in presence of 0.5 mM Fe(CN)\u003csub\u003e6\u003c/sub\u003e\u003csup\u003e3−\u003c/sup\u003e/Fe(CN)\u003csub\u003e6\u003c/sub\u003e\u003csup\u003e4−\u003c/sup\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/738410f556a8bcf2e4013512.png"},{"id":43147749,"identity":"af0d6297-3def-4618-9e4f-720d2de9b8bd","added_by":"auto","created_at":"2023-09-14 17:21:30","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":52688,"visible":true,"origin":"","legend":"\u003cp\u003eCVs recorded in KCl 0.1 M containing \u003cstrong\u003eA)\u003c/strong\u003e acetate pH 3 at scan rate 100 mV/s, \u003cstrong\u003eB)\u003c/strong\u003e 0.01M phosphate buffer pH 7 at scan rate 10 mV/s (solid line) and 100 mV/s (inset dashed line); NaOH pH 11.8 at scan rate \u003cstrong\u003eC\u003c/strong\u003e) 100 mV/s and \u003cstrong\u003eD\u003c/strong\u003e) 10 mV/s; at bare GCE (a), ZA-GCE (b) and ZA-ACB/GCE (c) containing 1mM AC\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/470dbcd91a0029738e853682.png"},{"id":43146133,"identity":"a7c30e56-8407-4f17-8e05-10759a6f7691","added_by":"auto","created_at":"2023-09-14 17:05:30","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":23701,"visible":true,"origin":"","legend":"\u003cp\u003eCVs recorded in 0.04 M RB (pH 3) containing 98 µM AC and 202.8 µM µM CAF at (a) bare GCE, (b) ZA/GCE and (c) ZA-ACB/GCE.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/8316ce62f72bf8215884f0ce.png"},{"id":43146739,"identity":"b50cb7e9-d1dd-4adb-838f-883adc02f409","added_by":"auto","created_at":"2023-09-14 17:13:31","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":31823,"visible":true,"origin":"","legend":"\u003cp\u003eCyclic voltammograms recorded on ZA-ACB/GCE in 0.04 M RB (pH 3) at different scan rates containing \u003cstrong\u003eA)\u003c/strong\u003e 105 µM AC and \u003cstrong\u003eB\u003c/strong\u003e) 110 µM CAF. Inset show plot of peak currents \u003cem\u003evs\u003c/em\u003ethe square root of scan rate. \u003cstrong\u003e(C)\u003c/strong\u003ePlot of log I versus log \u003cem\u003ev\u003c/em\u003e for \u003cstrong\u003e(a)\u003c/strong\u003e AC and \u003cstrong\u003e(b)\u003c/strong\u003e CAF.\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/87208695b0e071eff19f6f69.png"},{"id":43146738,"identity":"fbd7bfff-210e-4006-b125-60e96c9c986b","added_by":"auto","created_at":"2023-09-14 17:13:30","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":29960,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eA) \u003c/strong\u003eCVs recorded on ZA-ACB in 0.04 M RB solution at different pH and containing 99 µM of AC and 225.5 µM of CAF. \u003cstrong\u003eB)\u003c/strong\u003e Plot of the anodic peak currents \u003cem\u003evs\u003c/em\u003e pH for a) CAF and b) AC; plot of b) E\u003csub\u003e1/2-AC \u003c/sub\u003eand c) E\u003csub\u003epa-CAF \u003c/sub\u003e\u003cem\u003evs\u003c/em\u003e pH\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/a964886138bac64626d36fd9.png"},{"id":43147752,"identity":"ae08b368-4c8f-41ba-920c-f89fcea9990b","added_by":"auto","created_at":"2023-09-14 17:21:31","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":45560,"visible":true,"origin":"","legend":"\u003cp\u003eDPVs recorded in 0.04 M RB (pH 3) at ZA-ACB/GCE with successive addition of \u003cstrong\u003eA\u003c/strong\u003e) AC from 0.5-89 µM, \u003cstrong\u003eB\u003c/strong\u003e) CAF from 5-99 µM, \u003cstrong\u003eC\u003c/strong\u003e) AC with constant concentration of CAF (89µM), \u003cstrong\u003eD)\u003c/strong\u003e CAF with constant AC (87.6µM) and E) simultaneous addition of AC and CAF. The insets show the corresponding calibration curve.\u003c/p\u003e","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/435f221c5bd0e65e3b601c2c.png"},{"id":43146743,"identity":"8eaa51a0-69de-47a7-87e2-792bfb986f62","added_by":"auto","created_at":"2023-09-14 17:13:31","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":9362,"visible":true,"origin":"","legend":"\u003cp\u003eDPVs recorded in RB pH 3 containing \u003cstrong\u003e2\u003c/strong\u003e40 µM of CAF and 85 µM of AC at ZA-ACB/GC under the same experimental conditions.\u003c/p\u003e","description":"","filename":"8.png","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/0d62383119c0e43bf2f5d4b4.png"},{"id":52432112,"identity":"63e32247-1858-42c0-8a6a-30b6bee91e55","added_by":"auto","created_at":"2024-03-11 15:10:59","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1550677,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/0a0f2230-62fe-4762-91ee-750cff26984d.pdf"},{"id":43146744,"identity":"0a9251a4-d823-44ac-a5c5-f3d4731ca263","added_by":"auto","created_at":"2023-09-14 17:13:31","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":2623526,"visible":true,"origin":"","legend":"","description":"","filename":"SUPPORTINGINFORMATION.docx","url":"https://assets-eu.researchsquare.com/files/rs-3338753/v1/78c6f2b329daa851b8224a4a.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Polymer free Nanocomposite from Zeolite and Carbon Black as Glassy Carbon modifier platform for Simultaneous Electrochemical Quantification of Acetaminophen and Caffeine","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAcetaminophen or N-acetyl-p-aminophenol is a nonopioid non-NSAID (nonsteroidal anti-inflammatory drug) with analgesic and antipyretic action widely used to reduce fever and/or against mild to moderate pain associated to backache, headache, arthritis and postoperative pain[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Acetaminophen (AC) presents some side effects including the alteration of renal function and the inhibition of induction of labour[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. In order to increase its efficiency without increasing the side effect, acetaminophen has been combined to opioids such as codeine, hydrocodone, and oxycodone. Unfortunately, this has led to an augmentation in the utilisation and misuse of opioids[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Moreover these combination induced some side effects with the long-time used[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Because of these limitations, a central nervous system stimulant: caffeine (CAF), has been used as adjuvant [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. The presence of caffeine as adjuvant in paracetamol drug showed the enhancement and the prolonged analgesic activity of paracetamol and favoured its absorption[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. It is therefore an increasing necessity to develop methods for the selective and sensitive detection and quantification of AC and/or CAF in biological fluid as well as in pharmaceutical formulations. Thus, for this purpose several successful methods have been developed including chromatography and UV-spectrophotometry [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], despite the fact they are costly and may require sample pre-treatment and long time. Alongside of these methods, electrochemical methods have immerged a cheap, simple, rapid, sensitive and accurate for the determination of AC and CAF. However the use of classical electrodes was limited by high positive oxidation potential of caffeine, electrode fouling by the product of the oxidation of acetaminophen and low reproducible analysis [\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In order to overcome these drawbacks and improve the electrochemical sensitivity and selectivity, modified solid electrode substrate using different type of materials have been developed. Among the modifiers, zeolites occupy a prominent place because of their interesting physicochemical properties [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eZeolite modified electrodes have attacked the attention of researchers in recent years as evidenced by considerable progresses observed in this field [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Conventional zeolites which generally exists as fine powder made of crystals of microscopic size are easily incorporated in carbon paste to obtained carbon paste electrodes. Despite the insulating character of the zeolite, zeolite modified film electrodes have been reported in the literature and required the use of a binder (generally polymer) acting as sticker of zeolite particle together and favoured a thin layer on the electrode substrate [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Although the resulting polymer zeolite film electrodes were successfully applied, they are poorly mechanical stable and generally irreproducible, as reported by Shaw et al [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These limitations have been overcome by using nanozeolite or metal doped zeolite, but still required polymers to form a stable film electrode on various conductive substrate. In addition, the metal precursors used to prepare zeolites modified electrode are of a high cost, a limited availability, low selectivity, poor durability and often not respectful of the environment, [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the present work an eco-friendly nanocomposite was prepared by mixing high surface area nanozeolite A with acetylene carbon black. The as-synthesised nanocomposite was used to form by drop coating onto GCE\u0026rsquo;s surface, a stable thin film without any binder. Taking advantage of excellent electrical conductivity offered by acetylene carbon black [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] and large specific surface area nanosize zeolite, the composite modified electrodes were successfully applied in the individual and simultaneous quantification of AC and CAF in aqueous milieu. The developed sensors were successfully used for the simultaneously quantification of the both analytes in drugs formulations.\u003c/p\u003e"},{"header":"Experimental Section","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e1.1. Materials and chemicals\u003c/h2\u003e \u003cp\u003eThe nanozeolite type A denoted \u0026ldquo;ZA\u0026rdquo; used as one composite constituent was synthesised as described in our previous work using beneficiated rich quartz kaolin as silicon and aluminium sources [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Acetylene carbon black (AcB), K\u003csub\u003e3\u003c/sub\u003eFe(CN)\u003csub\u003e6\u003c/sub\u003e (\u0026gt;\u0026thinsp;99%), phosphoric acid (H\u003csub\u003e3\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e, 85%) and N,N dimethylformamide (DMF, 99.8%) were purchased from Abcr. Caffeine (C\u003csub\u003e8\u003c/sub\u003eN\u003csub\u003e4\u003c/sub\u003eO\u003csub\u003e2\u003c/sub\u003eH\u003csub\u003e10\u003c/sub\u003e, anhydrous powder 99%), acetaminophen (95%), potassium chloride (KCl, 99%), acetic acid (CH\u003csub\u003e3\u003c/sub\u003eCOOH, 99%), boric acid (H\u003csub\u003e3\u003c/sub\u003eBO\u003csub\u003e3,\u003c/sub\u003e 99.99% ) and NaOH (97%) were from STREM chemical. The Britton\u0026ndash;Robinson buffer (BRB) solution in the pH range from 2 to 9 was prepared by mixing H\u003csub\u003e3\u003c/sub\u003eBO\u003csub\u003e3\u003c/sub\u003e, H\u003csub\u003e3\u003c/sub\u003ePO\u003csub\u003e4\u003c/sub\u003e and CH\u003csub\u003e3\u003c/sub\u003eCOOH in deionized water. The desired pH was obtained by adjusting the pH solution with 0.2 M NaOH.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e1.2. Preparation of acetylene carbon black-zeolite composite\u003c/h2\u003e \u003cp\u003eThe composite ZA-AcB was prepared by the combination of AcB with ZA. Firstly, a homogenous ZA\u0026rsquo;s suspension (2g/L) was prepared by dispersing ZA in dimethylformamide. To this suspension a given amount of AcB (2.5, 5, 10, 20 and 30%wt) was then added to ZA\u0026rsquo;s suspension under vigorous stirring. This mixture was sonicated for 30 min and then kept under stirring for 24 hours.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e1.3. Instruments\u003c/h2\u003e \u003cp\u003eX-ray diffraction analysis was performed using a STOE Stadi-p X-ray powder diffractometer (Stoe \u0026amp; Cie GmbH, Darmstadt, Germany), with Cu Kα1 radiation (40 kV, 30 mA, and λCu\u0026thinsp;=\u0026thinsp;1.54056 \u0026Aring;). The material\u0026rsquo;s morphology was obtained with scanning electron microscope (Amray 1610 Turbo, Anray Inc., Bedford, MA, USA) at an accelerating voltage of 15 kV. The EDX mapping was performed on Fiel-emission scanning electron microscopy equipped with energy-dispersive X-ray (EDX) spectroscopy. The surface area and porosity were determined by nitrogen adsorption\u0026ndash;desorption isotherms recorded at 77K using a Micromeritics analyser (Termo Electron Corporation, Germany). The thermal gravimetric analysis (TGA) was performed on TA Instruments TGA, Netzsch under nitrogen atmosphere, with a heating rate of 10\u003csup\u003eᵒ\u003c/sup\u003eC.min\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. Electrochemical measurements were conducted on Corrtest Electrochemical Workstation and \u0026micro;-Autolabpotentiostat/galvanostat equipped with CS Studio 5 and GPES (General Purpose Electrochemical System) respectively, in a conventional three electrodes cell with a saturated calomel electrode as reference electrode, a platinum wire as counter electrode and either bare or modified glassy carbon as working electrode. Genesys 10S Thermo Scientific spectrophotometer was used to collect UV-vis spectra.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e1.4. Preparation of the working electrodes\u003c/h2\u003e \u003cp\u003eA glassy carbon electrode (GCE) was used as working electrode substrate. Prior its use, GCE was polished on a mirror-like surface with aqueous alumina slurry of three grain sizes (1, 0.3 and 0.05 \u0026micro;m) on individual wet polishing cloth, followed by thorough rinsing with distilled water. After that, the electrode was sonically cleaned in 1:1 water-ethanol for 20 minutes to remove any traces of alumina. ZA and ZA-AcB film working electrodes were prepared by drop coating a given volume of either ZA-AcB or ZA suspension (2 g/L) onto GCE surface, and the coating was allowed to dry at room temperature for one hour and rinsed with distilled water before use. The resulting electrodes are denoted ZA/GCE when the zeolite suspension was used and ZA-AcB/GCE when the composite suspension was dropped.\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section3\"\u003e \u003ch2\u003e1.5. Real sample preparation\u003c/h2\u003e \u003cp\u003eThree commercial brands tablets containing AC and CAF namely \u003cem\u003ePanadol\u003c/em\u003e (500 mg of paracetamol and 65 mg of caffeine), \u003cem\u003eIbex\u003c/em\u003e (325 mg paracetamol and 30 mg caffeine) and \u003cem\u003eDolimex\u003c/em\u003e (500 mg of paracetamol and 50 mg of caffeine) purchased in local pharmacy were used as real samples. The real sample\u0026rsquo;s solution was prepared by dissolving fine powdered tablet in distilled water. Then x microliter of the dissolved drug was then transferred into 10 mL volumetric flask and dissolved with BRB (pH 3). For UV analysis, the preparation of the real sample analyte follows the same procedure as described above.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Results and discussion","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.1. Physicochemical characterisation of zeolite-carbon composite\u003c/h2\u003e \u003cp\u003eThe XRD pattern of ZA-AcB composite (spectrum a in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA) shows 2θ peaks (7.24°, 10.2°, 12.5°, 16.2°, 20.4°, 21.64°, 23.97°, 26.14°, 27.32°, 31.03°, 32.72°, 33.43° and 34.2° ) well aligned on those of characteristic peaks of zeolite type A (spectrum c in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eA) reported in our previous work[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], the first four peaks being increased slightly. In addition, two broad peaks clearly observed at 2θ equal to 25.77° and 43.21° on spectrum b attributed to the hexagonal graphitic structure of the carbon black [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], are absent on pattern of pristine zeolite and that of the composite. These results suggest that ZA has likely embedded the amorphous carbon without loss of their respective structural integrity as reported in the literature [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] and AcB being located in the zeolite interparticle spaces. The average crystallite size of the composite was estimated using Sherrer’s equation utilising XRD data and was found to be \u003cem\u003eca\u003c/em\u003e 59.62 nm, close to the average crystallite size of the pristine zeolite reported in our previous work [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe FTIR spectrum of ZA-AcB (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eB, plot a) exhibited zeolite type A’s characteristic bands as do pristine ZA [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eB, plot c) in addition to characteristic bands of chemical function of acetylene black (at 1550, 1150 and 1050 cm\u003csup\u003e− 1\u003c/sup\u003e corresponding to C = C, C-OH and C-O-C, respectively[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].) as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eB (plot b). Interestingly, two bands at 2922 and 2850 cm\u003csup\u003e− 1\u003c/sup\u003e attributed to –C-H- bond [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] absent on the spectra of ZA and ACB were observed on the spectrum of the composite.\u003c/p\u003e \u003cp\u003eThe surface morphology of the composite and pristine zeolite was investigated by scanning electronic microscopy (SEM). Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eC and D present respectively, the SEM images of pristine zeolite and zeolite acetylene carbon black composite. In Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eD, one can observe clearly a well-defined cubic shape characteristic of zeolite type A (similar with that observed on the image of pristine zeolite in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eC) with uniformly distributed aggregate of carbon black particles. These observations indicate that the zeolite shape was not affected by the presence of carbon. The elemental mapping of ZA-AcB (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eE) shows a homogeneous distribution of AcB within the composite highlighted by the green colour corresponding to carbon (E-1), the red colour to oxygen (E-2), bleue cyan to sodium (E-3), bleue to aluminium (E-4) and orange to silicium (E-5). EDX analysis results exhibited in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003eF confirms that the composite was made of oxygen (27%), silicon (25%), aluminium (23%), sodium (15%) and carbon (10%).\u003c/p\u003e \u003cp\u003eThe BET surface area and pore volume of the composite were found to be 27.98 m\u003csup\u003e2\u003c/sup\u003e/g and 0.037 cm\u003csup\u003e3\u003c/sup\u003e/g; respectively. The results are \u003cem\u003eca\u003c/em\u003e 50% of those of pristine zeolite reported previously [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], likely because AC has blocked or/and filled some zeolite micropore by creating a heterogeneous environment within the composite [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"MOESM1\" class=\"InternalRef\"\u003eS1\u003c/span\u003e presents the thermal gravimetry analysis of the composite (curve a) and the pristine zeolite (curve b). Both materials present two main weight loss changes, the first at temperature range 60°C − 200°C and the second at 200°C – 400°C related respectively, to the loss of adsorbed water and water forming the hydration complexes with cations located in the cages of the zeolite[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. It is worth noted that ZA-AcB displayed a weight first loss of \u003cem\u003eca\u003c/em\u003e 13% and the second loss of \u003cem\u003eca\u003c/em\u003e 2% lower than 17% and 4% obtained for pristine ZA. This behavior is attributed to the decreases of the composite’s micropore volume created by its heterogeneous structure leading to the decreases in moisture loss [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.2. Electrochemical characterisation of ZA-AcB/GCE\u003c/h2\u003e \u003cp\u003eThe ability of the pristine zeolite and the composite to form a stable film onto glassy carbon electrode has been tested using cyclic voltammetry (CV) in diluted solution of [Fe(CN)6]\u003csup\u003e3−\u003c/sup\u003e as redox probe. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003e shows the multistep voltammetry recorded at modified and unmodified electrodes at 50 mV.s\u003csup\u003e− 1\u003c/sup\u003e. As expected, at pristine zeolite modified GCE (namely ZA/GCE), CVs recorded shows poorly defined redox peak of [Fe(CN)\u003csub\u003e6\u003c/sub\u003e]\u003csup\u003e3−\u003c/sup\u003e which is due to the electrostatic repulsion between negatively charged ZA film and the anionic probe. Thus, ZA film onto GCE acts as barrier vis-a-vis of redox probe, preventing the diffusion of [Fe(CN)6]\u003csup\u003e3−\u003c/sup\u003e to the glassy carbon electrode. In contrast, when GCE was coated with the composite film, a simultaneous growth of cathodic and anodic peaks was observed upon repetitive scan potential and reached a steady state after 30 cycles, indicating the accumulation of the negative probe within the composite film. Moreover, the maximum steady state exhibited peak to peak potential separation ∆E = 100 mV and peak current ratio Ipc/Ipa ≈ 1; illustrating a quasi-reversible process. Interestingly the maximum steady state current recorded at ZA-AcB/GCE was four time higher that that obtained at bare GCE. All these results clearly demonstrated: (i) the stability of the composite film and its pre-concentration capability of the negative probe despite the presence of the negatively charged zeolite within the film and (ii) the presence of AcB within the film thanks to its electronic conductivity and its pore, which favoured the diffusion of the probe to the GCE.\u003c/p\u003e \u003cp\u003eThe electron transfer property of the modified electrodes was studied using electrochemical impedance spectroscopy (ESI). The Nyquist plots of EIS recorded in 0.1 M KCl solution containing 0.5 mM of [Fe(CN)\u003csub\u003e6\u003c/sub\u003e]\u003csup\u003e3−/4−\u003c/sup\u003e ions are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e2\u003c/span\u003eE. The Nyquist plot recorded at ZA/GCE (curve a), exhibited the largest semi-circle i.e largest charge transfer resistance (Rtc = 9.1 kΩ) compared with those recorded at bare GCE (Rtc = 3 kΩ) and at ZA-AcB/GCE (Rtc = 1.5 kΩ), indicating that the electron transfer rate is faster at composite modified electrode. These results are in accordance with CV result.\u003c/p\u003e \u003cp\u003eThe effective surface area of the modified electrode was evaluated by applying the Randles Sevcik equation (Eq.\u0026nbsp;1) using data obtained from the study of the effect of the scan rate on the electrochemical response recorded in [Fe(CN)\u003csub\u003e6\u003c/sub\u003e]\u003csup\u003e3−\u003c/sup\u003e at ZA-AcB/GCE as shown in Fig. S3:\u003c/p\u003e \u003cp\u003eIp = 2.69×10\u003csup\u003e5\u003c/sup\u003e× (D\u003csub\u003e0\u003c/sub\u003e)\u003csup\u003e1/2\u003c/sup\u003e·A·v\u003csup\u003e1/2\u003c/sup\u003e·n\u003csup\u003e3/2\u003c/sup\u003e·C\u003csub\u003e0\u003c/sub\u003e (Eq.\u0026nbsp;1)\u003c/p\u003e \u003cp\u003eHere, for [Fe(CN)\u003csub\u003e6\u003c/sub\u003e]\u003csup\u003e3−\u003c/sup\u003e/[Fe(CN)\u003csub\u003e6\u003c/sub\u003e]\u003csup\u003e4−\u003c/sup\u003e, n = 1, C\u003csub\u003e0\u003c/sub\u003e = 5.10\u003csup\u003e− 7\u003c/sup\u003e mol.cm\u003csup\u003e− 3\u003c/sup\u003e, D\u003csub\u003e0\u003c/sub\u003e = 7.6×10\u003csup\u003e− 6\u003c/sup\u003e cm\u003csup\u003e2\u003c/sup\u003e.s\u003csup\u003e− 1\u003c/sup\u003e [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. From the slope obtained by plotting Ipa \u003cem\u003evs. v\u003c/em\u003e\u003csup\u003e1/2\u003c/sup\u003e (inset Fig.S3C), the effective surface area of ZA-AcB/GCE was estimated to be 0.0035 cm\u003csup\u003e2\u003c/sup\u003e, which is 3 time that of bare GCE.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003cdiv class=\"BlockQuote\"\u003e\u003c/div\u003e\u003cp\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e\u003c/p\u003e \u003c/div\u003e"},{"header":"Application of the composite modified electrode to the electroanalysis of acetaminophen and caffeine","content":"\u003cp\u003eThe electrochemical behavior of AC and CAF was study at modified electrode ZA/GCE and ZA-AcB/GCE. Because AC\u0026rsquo;s electrochemical oxidation is known to very often parallel some catalyzed oxidation in the organism[\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e], thus it was very important to study its oxidation which strongly depends on the solution\u0026rsquo;s pH [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\n\u003ch2\u003e3.1. Electrochemical behaviour of acetaminophen at ZA-AcB/GCE\u003c/h2\u003e\n\u003cp\u003eThe electrochemical oxidation of AC was study in various pHs (3.0, 7.0 and 11.8) utilizing cyclic voltammetry. Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e shows the cyclic voltammograms recorded at bare GCE (curve a), ZA/GCE (curve b) and ZA-AcB/GCE (curve c) in various pH\u0026rsquo;s solution containing AC. One can observe that when the potential is scanned in the positive direction, the CVs recorded at modified and unmodified electrodes exhibited one main well defined oxidation peak with potential peak shifting as expected to positive potential when decreasing the solution\u0026rsquo;s pH. This observation indicates the participation of protons(s) in AC oxidation to N-acetyl-p-benzoquinone-imine (NAPQI) (see scheme \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e). Interestingly, in the reverse scan potential in acidic solution (pH 3.0) two reduction peak C1 and C2 were observed on CVs a), b) and c); C1 ill-defined corresponding to the reactivity of the electrochemical generated NAPQI[\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e] and C2 to the reduction of P-benzoquinone, P-benzoquinone being the product of successive chemical reactions in acidic condition of NAPQI (scheme \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). The dome (A2) observed in this CV (a) at \u003cem\u003eca\u003c/em\u003e\u0026thinsp;+\u0026thinsp;0.23 V in the positive potential scan may be the oxidation of the product of the p-benzoquinone electrochemical reduction. Moreover, it is worth noting that the current peaks corresponding to the oxidation of AC (A1) and to the reduction of p-benzoquinone (C2) recorded at ZA/GCE are greater than those recorded at bare GCE. This can be explained by the fact that in acidic media, AC (pKa 9.5) as well as NAPQI are positively charged, thus there will be a favorable electrostatic interaction between these products facilitating its detection at GCE. Indeed, since AC is essentially size excluded from zeolite A aperture (4\u0026Aring;) [\u003cspan class=\"CitationRef\"\u003e31\u003c/span\u003e], its cationic form is therefore more likely trapped on the external surface of the zeolite, thus improving its electrochemical reaction at zeolite-electrode-solution interface. This suggest an extrazeolitic mechanism of AC at ZA/GCE via ion exchange properties. Interestingly at ZA-AcB/GCE (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eA-c), the anodic peak current recorded is 1.5 time greater than that obtained at ZA-GCE. Thus, compared to GCE and ZA/GCE, there is a gain in potentials and current intensities at ZA-AcB/GCE, highlighting the good electrocatalytic activity of the composite modified electrode owing to the synergic effect of the nanoscale zeolite and high electron conductive carbon black.\u003c/p\u003e\n\u003cp\u003eIn phosphate buffer (pH 7.0), the CVs recorded at modified and unmodified GCE show one well defined oxidation peak when potential was scanned at either 10mVs\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB) or 100 mVs\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e (dashed plots inset Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB) in positively direction and one cathodic peak in the reversed potential scan. This quasi-reversible process corresponds to two electron electrochemical redox reaction of AC to NAQPI[\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]. In addition, for all the three voltammograms of Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eB, the current ratio Ip\u003csub\u003eC1\u003c/sub\u003e/Ip\u003csub\u003eA1\u003c/sub\u003e was found to be 0.15 at GCE, 0.44 at ZA/GCE and 0.65 at ZA-AcB/GCE, suggesting that part of NAPQI is likely involved in the chemical reaction leading to the formation of dimer (see scheme \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB). Interestingly one can note that the CV recorded at ZA-AcB/GCE at for example 10 mVs\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e exhibited the separation peak to peak potential ∆E was about 0.26 V about half that of those obtained at CV (a) and (b). Moreover, both the cathodic and anodic peak currents at CV (c) significantly increased compared with those recorded at ZA/GCE and bare GCE. All these results indicate that although the reaction mechanism of AC is the same at modified and unmodified electrodes, the presence of carbon black within the composite onto the electrode surface has favored the oxidation of AC to NAQPI and vice-versa, thus highlighting electrocatalytic of composite modified electrode toward the AC in this media.\u003c/p\u003e\n\u003cp\u003eFigure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eC and D presents, respectively the CVs recorded in alkaline media (pH 11.8) containing AC at modified and unmodified electrodes at 100 mVs\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e and at 10 mVs\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e. One can observed that the CVs recorded at unmodified GCE (curve a)) by scanning the potential at 100 mV s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e exhibits mainly a well-defined anodic peak A1 at +\u0026thinsp;0.30 V attributed to the oxidation of AC (1) to NAPQI (2) and two cathodic peak C1 and C2 at +\u0026thinsp;0.13 V and \u0026minus;\u0026thinsp;0.15 V respectively. The ill-defined peak C1 corresponds to the reduction of NAPQI (2) to AC[\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e] and C2 to the reduction of \u003cem\u003eO\u003c/em\u003e-benzoquinone (3) to N-(3,4-dihydroxyphenyl) acetamide (3-hydroxyacetaminophen) (4) [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]which oxidation (A2) is observed as a hump at \u0026minus;\u0026thinsp;0.04 V. At modified GCEs, the recorded CVs (curves b and c) are quite similar and exhibit an oxidation peak A1 and a reduction peak C1 as observed on CV (a) recorded at bare GCE and one reduction peak located respectively, at -0.19 V at ZA/GCE and at -0.13 V at ZA-AcB/GCE. These reduction peaks may be composite of C1 and C2 observed on CV (a). Interestingly, when the potential was scanned at low scan rate (\u0026lt;\u0026thinsp;50 mV.s\u003csup\u003e\u0026minus;\u0026thinsp;1\u003c/sup\u003e) with ZA-AcB/GCE and ZA/GCE, the reduction peak splitted in two reduction peaks namely C2 and C3 appearing, respectively at \u0026minus;\u0026thinsp;0.15 V and \u0026minus;\u0026thinsp;0.26 V (CV b) and c) in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eD), the oxidation peak being unchanged in term of potential. The peak C3 at \u0026minus;\u0026thinsp;0.26 V was likely attributed to the reduction of \u003cem\u003eP\u003c/em\u003e-benzoquinone (6) to N-(2,4,5- trihydroxyphenyl)acetamide (5) (reaction III), N-(2,4,5- trihydroxyphenyl)acetamide being obtained from (4) via the \u003cem\u003eMicheal\u003c/em\u003e addition of hydroxide ion [\u003cspan class=\"CitationRef\"\u003e30\u003c/span\u003e]. Thus, by lowering the potential scan rate, the product of reaction III may quantitatively present at the electrode interface and then led to the appearance of peak C3 (see Fig S3) corresponding to the reduction of compound (6) to compound (5). In addition, in the second potential scan (solid lines), a new anodic peak A3 appears at \u0026minus;\u0026thinsp;0.15 V, corresponding to the oxidation of (5). At bare GCE, the decrease in potential scan rate did not lead to any change in CV shape (CVs a) in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003eD). This behavior is a clear evidence of the good electrocatalytic properties of the composite modified electrode toward the electrochemical analysis of AC.\u003c/p\u003e\n\u003cp\u003eFrom the above study it appeared that in acid, neutral and alkaline media, the oxidation of AC to NAPQI was well defined with peak potential dependent of solution pHs.\u003c/p\u003e\n\u003cp\u003eIn order to avoid the effects related to the concentration of the analyte and to preserve the authenticity of the reactions taking place, the electroanalysis of AC was carried out in buffer medium. Robinson buffer solution (RB) offers a large range of pH ranging from 2 to 12, thus it was used to perform the next steps of this work. Prior to this, CVs recorded at ZA-AcB/GCE in RB containing AC were compared with those recorded in electrolyte solution pH 3 (Fig. SA), (Fig. S4B) and 11.8 (Fig. S4C) containing the same amount of AC. It is clearly observed that all the recorded CV at ZA-AcB/GCE exhibited the same shape with peak current as well as peak potential quite the same, indicating that the electrochemical signature of AC at quite identical in both media. From all these findings, it appears that the electroanalysis of AC at modified electrodes can be monitored by studying the main oxidation peak due to the electrochemical transformation of AC to NAQPI.\u003c/p\u003e\n\u003ch2\u003e3.2. Electrochemical behaviour of AC in presence of CAF at ZA-AcB/GCE\u003c/h2\u003e\n\u003cp\u003eAs reported in the literature, the electrochemical behaviour of CAF is well highlighted in acidic media [\u003cspan class=\"CitationRef\"\u003e32\u003c/span\u003e], thus the electrochemical behaviour of AC in the presence of CAF was studied in RB pH 3.0. Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e shows CVs recorded in 0.04 M RB (pH 3.0) containing a mixture AC (98 \u0026micro;M) and CAF (202.8 \u0026micro;M) at bare GCE (curve a), ZA/GCE (curve b) and ZA-AcB/GCE (curve c). It can be observed at modified and unmodified electrodes, the forward potential scan in the positive direction led to two oxidation peaks: the first at less positive potential corresponding to the oxidation of acetaminophen and the second at more positive potential to the oxidation of caffeine. On the reverse scan, one low and ill-defined reduction peak was observed on CVs recorded at bare GCE and ZA/GCE (\u0026thinsp;~\u0026thinsp;+\u0026thinsp;0.46 V) which corresponds to the reduction of NAPQI to AC as reported in section 3.1. Interestingly, at ZA-AcB/GCE, the recorded CV(curve c) displays a well-defined quasi-reversible process with redox peak centered at +\u0026thinsp;0.49 V with \u0026Delta;E\u0026thinsp;=\u0026thinsp;0.60 V (current ratio Ipc (3.5 \u0026micro;A)/Ipa (5.25 \u0026micro;A) equal to 0.7) while CAF undergoes an irreversible oxidation peak current at +\u0026thinsp;1.35 V. Furthermore, the oxidation peak potential of AC and CAF obtained on composite modified electrode are negatively shifted respectively for 38 mV and 32 mV of those recorded at bare GCE; and 53 mV and 40 mV of those recorded at ZA/GCE. Furthermore, the oxidation peaks current of AC and CAF recorded at ZA-AcB/GCE were respectively about 3.5 and 2 times greater than those obtained with bare GCE, 5 and 2.8 time greater than those recorded with ZA/GCE. Thus, the increase in peak current associated with the lowering potential demonstrated that the combination of nanozeolite with carbon black as an electrode modifier has an electrocatalytic activity towards the oxidation of both AC and CAF. This result is likely due on one hand to the favourable electrostatic interaction between cationic form of analytes and the negative charged of the nanoscale zeolite particles and on the second hand to the good electron conductor of AcB.\u003c/p\u003e\n\u003ch2\u003e3.3. Effect of scan rate\u003c/h2\u003e\n\u003cp\u003eThe relationship between the scan rate and voltammetric response gives informations about the nature of the electrochemical process occurring at nanocomposite modified electrode. Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eA and \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eB shows the CVs recorded at different scan rates in RB pH 3 containing a mixture of AC and CAF, respectively. From the CVs in shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e, one can note that the oxidation and reduction peak current increased as the scan rate increases for the both analytes and the plots of peak current versus square root of the scan rate resulted in a straight line (R\u0026sup2; = 0.998 for both analytes, inset Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e). The obtained linearity suggests that the electrochemical process governing the charge transfer is the diffusion of analytes. Additionally, the slope of log of peak current versus log of scan rate is 0.42 for CAF (line a in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eC) and 0.38 and 0.50 for AC (lines b and c, Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003eC) respectively. These values are close to the theoretical value 0.50 expected for diffusion-controlled electrode process [\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e, \u003cspan class=\"CitationRef\"\u003e34\u003c/span\u003e]. This confirms that the electrochemical oxidation of these analytes was predominantly governed by an apparent diffusion process.\u003c/p\u003e\n\u003ch2\u003e3.4. Effect of pH\u003c/h2\u003e\n\u003cp\u003eIn order to determine the optimal pH and confirm the involvement of proton in the electrochemical reaction, the effect of the buffer\u0026rsquo;s pH on the sensitivity of ZA-AcB/GCE towards both analytes was investigated in RB\u0026rsquo;s pH ranging from 2 to 9 containing the mixture of analytes (225.5 \u0026micro;M CAF and 99 \u0026micro;M AC). Figure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eA presents the CVs recorded at ZA-AcB/GCE. As can be observed the cathodic and anodic peak potential shifted positively with pH increase. As shown in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eB, the plots of I\u003csub\u003epa\u003c/sub\u003e versus pH indicate that the oxidation peak current is affected by electrolytic solution\u0026rsquo;s pH (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eB curve a for AC and curve b for CAF), the higher peak current being obtained at pH 3. Therefore, pH 3 was chosen for the electroanalytical experiments of the both analytes. In addition, the plots of E\u003csub\u003e1/2\u003c/sub\u003e and Ep\u003csub\u003ea\u003c/sub\u003e versus pH result in a linear regression (Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003eB) as presented by plot c for AC and plot d for CAF, respectively. The corresponding linear equations are as follows:\u003c/p\u003e\n\u003cp\u003eE\u003csub\u003e1/2,AC\u003c/sub\u003e = -0.053 pH\u0026thinsp;+\u0026thinsp;0.68 (R\u0026sup2;= 0.974) (Eq.\u0026nbsp;2)\u003c/p\u003e\n\u003cp\u003eE\u003csub\u003ep,CAF\u003c/sub\u003e = -0.015 pH\u0026thinsp;+\u0026thinsp;1.42 (R\u0026sup2;= 0.970) (Eq.\u0026nbsp;3)\u003c/p\u003e\n\u003cp\u003eThe value of slope of Eq.\u0026nbsp;2, 53 mV/pH obtained for AC is close to the theoretical value 59 mV/pH corresponding to the involvement of equal number of electron and proton, thus for two electrons involved in the electrochemical reaction of AC, they are accompanied by two protons (scheme \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eA). For CAF, the slope of Eq.\u0026nbsp;3 is 15 mV/pH as reported elsewhere[\u003cspan class=\"CitationRef\"\u003e35\u003c/span\u003e\u0026ndash;\u003cspan class=\"CitationRef\"\u003e37\u003c/span\u003e], suggesting there is not an equal number of proton and electrons involved in the oxidation of CAF in opposition to CAF\u0026rsquo;s electrochemical reaction exhibited in scheme \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003eB. Even if the reason of the behaviour is not yet well known, it appeared that the electrooxidation of CAF at ZA-AcB/GCE is more complex.\u003c/p\u003e\n\u003cp\u003e\u003cspan\u003e\u003cstrong\u003e3.5 Effect the amount of acetylene carbon black and the film thickness\u003c/strong\u003e.\u003cbr\u003e\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003eThe influence of the amount of AcB within the film composite onto GCE on the sensitivity of the composite modified GCE towards AC and CAF was investigated using DPV by varying the amount of AcB from 0 to 30 wt% used in the preparation of the composite. From this graph, on can observed that the electrochemical response of the oxidation of AC and CAF varied when different ZA-AcB/GCE prepared using composite with different AcB content were used to record the response in the same solution ( RB pH3 containing fix concentration of AC and CAF). The results are presented in Figure S5-A (curve a for AC and curve b for CAF). They show that the oxidation peak current of the both compounds increased with AcB content in the composite film GCE and the maximum current was obtained when the composite film was made with a composite containing 10% of AcB then levelled off. This can be explained by the fact that the high content of AcB may lead to less stable film due to its hydrophobicity. Thus, the film was further prepared using composite made of 10% of AcB.\u003c/p\u003e\n\u003cp\u003eThe effect of suspension\u0026rsquo;s volume allowed to dry on the sensitivity of the composite film electrode was investigated in the range of 1.5\u0026micro;L-7.5\u0026micro;L of the 10% AcB /ZA suspension. Figure S5-B depicts the effect of anodic peaks current (for AC (curve a) and CAF (curve b)) versus volume of the suspension\u0026rsquo;s volume. As can be seen, the oxidation current peak of the both analytes increased with the volume of the suspension of ZA/AcB and reached the maximum for 5\u0026micro;L of the suspension and then decreased for higher volume. The slight decrease of the electrochemical response could be the result of the larger film thickness which becomes not only unstable but also resistant to the diffusion of analytes onto the surface of the electrodes.\u003c/p\u003e\n\u003ch2\u003e3.6. Individual and simultaneous determination of AC and CAF\u003c/h2\u003e\n\u003cp\u003eFigure\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eA shows the DPVs recorded at ZA-AcB/GCE in RB pH 3 in which successive addition of either AC or CAF were added. One can observe that the electrochemical oxidation current in each case increased when the concentration of the analyte was increased. It was observed that the oxidation peak current was linearly dependent on the concentration of AC ranging from 0.5 to 89 \u0026micro;M (see inset Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eA) and from 5 to 99 \u0026micro;M (see inset Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eB) for the CAF with regression equations:\u003c/p\u003e\n\u003cp\u003eIp\u0026thinsp;=\u0026thinsp;0.052 [AC]\u0026thinsp;+\u0026thinsp;0.010 (R\u0026sup2; = 0.994) (Eq.\u0026nbsp;4)\u003c/p\u003e\n\u003cp\u003eIp\u0026thinsp;=\u0026thinsp;0.040 [CAF] \u0026minus;\u0026thinsp;0.236 (R\u0026sup2; = 0.999) (Eq.\u0026nbsp;5)\u003c/p\u003e\n\u003cp\u003eInterestingly when successive additions of AC were made into the electrolyte containing fix concentration of CAF (89 \u0026micro;M), the oxidative peak current of AC increased synchronously while the CAF\u0026rsquo;s oxidation current remained constant (see Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eC). Similar behaviour was observed when increasing concentration of CAF was added to the electrolytic solution containing fix concentration of AC (87.6 \u0026micro;M) (see Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eD). These increases are linearly depended on the concentration of each added analyte with regression equations:\u003c/p\u003e\n\u003cp\u003eIp\u0026thinsp;=\u0026thinsp;0.057 [AC] \u0026ndash; 0.846 (R\u0026sup2;= 0.994) (Eq.\u0026nbsp;6)\u003c/p\u003e\n\u003cp\u003eIp\u0026thinsp;=\u0026thinsp;0.443 [CAF] \u0026ndash; 0.330 (R\u0026sup2;= 0.997) (Eq.\u0026nbsp;7)\u003c/p\u003e\n\u003cp\u003eIt is worth noted that the sensitivities of ZA-AcB/GCE obtained for individual addition of each analyte and for addition of one analyte in presence of each other was found to be quite close. These results demonstrate that the prepared sensors are a promising candidate for individual and simultaneous detection of AC and CAF without any interference. The detection limit based on S/N\u0026thinsp;=\u0026thinsp;3 was estimated to be 0.38 \u0026micro;M and 0.82 \u0026micro;M for AC and CAF respectively.\u003c/p\u003e\n\u003cp\u003eFurther, the simultaneous addition of AC and CAF in RB pH 3 has led to two well resolved independent oxidation peak at +\u0026thinsp;0.51 V for the electro oxidation of AC and +\u0026thinsp;1.36 V electro-oxidation for CAF as shown in Fig. \u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003eE. The peak current increased with continuous addition of the both analytes and the peak current were linearly depended on the concentration of each analyte from 11 to 80 \u0026micro;M for AC (R\u0026sup2;= 0.997) and 20 to 134 \u0026micro;M for CAF (R\u0026sup2;= 0.994) with sensitivity of 0.056 \u0026micro;A/\u0026micro;M and 0.051 \u0026micro;A/\u0026micro;M for AC and CAF, respectively. Thus, the oxidation peak potentials of the obtained DPVs as well as their sensitivities match well with those obtained with individual analyte.\u003c/p\u003e\n\u003cp\u003eThe comparison of the performances of ZA-AcB/GCE and other electrodes reported for determination of acetaminophen and caffeine described in the literature are listed in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. It is clearly noted that the developed sensors have appreciable linear range with a detection limit of the same order of magnitude and even lower than some of previously reported works.\u003c/p\u003e\n\u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe comparison of the analytical performances of ZA-AcB/GCE for caffeine and paracetamol determination with previously reported electrodes.\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eElectrodes\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMethod\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAnalytes\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLinear range (\u0026micro;M)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDetection limit (\u0026micro;M)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eReferences\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eNafion\u0026reg;HNT/GCE \u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6\u0026ndash;14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.6\u0026ndash;20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.173\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003epoly(AHNSA)/GCE \u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSWV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u0026ndash;125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u0026ndash;125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.79\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eaGCE \u003csup\u003e3\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eSWV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u0026ndash;180\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.55\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u0026ndash;95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.36\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eLt/fMWCNT/MGCE \u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.9\u0026ndash;80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u0026ndash;110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.54\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eCS-Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003eNP/GCE \u003csup\u003e5\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50-2000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u0026ndash;900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e23\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eGC-SnS/TiO\u003csub\u003e2\u003c/sub\u003e-GO \u003csup\u003e6\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.009-280\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.0166-333\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eMOF-199/Naf-GCE \u003csup\u003e7\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e36\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.2\u0026ndash;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003ePT/TiO\u003csub\u003e2\u003c/sub\u003e-Gr/GCE \u003csup\u003e8\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.1\u0026ndash;90\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.034\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e[\u003cspan class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.25\u0026ndash;200\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eZA-AcB/GCE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eDPV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.5\u0026ndash;89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eThis work\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u0026ndash;99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.82\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003e\u003csup\u003e1\u003c/sup\u003e Nafion halloysite nanotube modified glassy carbon electrode; \u003csup\u003e2\u003c/sup\u003e Poly(4-amino-3-hydroxynaphthalene sulfonic acid)-modified glassy carbon electrode; \u003csup\u003e3\u003c/sup\u003e activated glassy carbon electrode; \u003csup\u003e4\u003c/sup\u003e Luteolin on functionalized multi-wall carbon nanotube modified glassy carbone electrode ; \u003csup\u003e5\u003c/sup\u003e cassava starch-Fe\u003csub\u003e3\u003c/sub\u003eO\u003csub\u003e4\u003c/sub\u003e nanoparticles modified glassy carbone electrode; \u003csup\u003e6\u003c/sup\u003e Tin sulphite (SnS) and titanium dioxide (TiO\u003csub\u003e2\u003c/sub\u003e) on grapheme oxide (GO) sheets modified glassy carbon electrode; \u003csup\u003e7\u003c/sup\u003emetal organic framework-199/nafion modified glassy carbon electrode; \u003csup\u003e8\u003c/sup\u003e Poly(taurine)/TiO\u003csub\u003e2\u003c/sub\u003e graphene composite modified glassy carbon electrode\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003ch2\u003e3.7. Reproducibility, stability and Interferences study of ZA-AcB/GCE\u003c/h2\u003e\n\u003cp\u003eThe reproducibility of ZA-AcB/GCE was evaluated by carrying out repetitive measurement-regeneration cycles. The results of the respective measurements recorded in RB\u003c/p\u003e\n\u003cp\u003e(pH 3.0) containing 240 \u0026micro;M of CAF and 85 \u0026micro;M of AC are presented in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e8\u003c/span\u003e. The DPVs obtained display a relative standard deviation of 6.5% and 4.6% for AC and CAF respectively. This suggests that the prepared sensor exhibited a good reproducibility performance toward the simultaneous detection of these compounds. The results obtained in Fig.\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e above confirm the good operational stability of the composite modified glassy carbon electrode. The developed sensors have proven 95% of repeatability after one week of use.\u003c/p\u003e\n\u003cp\u003eThe interference effects of potentially interfering substances on the DPV response of AC and CAF at ZA-AcB/GCE were evaluated. Figure S6 shows DPVs of AC and CAF simultaneously introduces gradually from 2\u0026ndash;22 \u0026micro;M and 20\u0026ndash;220 \u0026micro;M respectively, in RB (pH 3) containing 280 \u0026micro;M of ascorbic acid (AA), glucose (Glu) and tyrosine (Tyr). It is clearly observed that current peak due to the oxidation of AC and CAF increased as their concentration increased. This result shows that none of the foreign molecules significantly interfered with AC and CAF (signals change below 5%) except UA (\u0026gt;\u0026thinsp;50 \u0026micro;M) was found to interfere with AC. This confirms the good selectivity of ZA-AcB/GCE in complex solution toward simultaneous detection of AC and CAF.\u003c/p\u003e\n\u003ch2\u003e3.8. Simultaneous quantification of AC and CAF in pharmaceuticals formulations\u003c/h2\u003e\n\u003cp\u003eThe developed sensors were also applied for the quantification of AC and CAF in tablets containing the both analytes using standard addition method. Each analyte was analysed by introducing a known amount of tablet sample analytes in voltametric cell and the corresponding DPVs recorded. This was followed by 3 successive simultaneous additions of AC and CAF standard solution and the resulting DPVs (added real sample: dashed line and standard solution: solid line) are presented in figure S7-A, S7-B and S7-C for \u003cem\u003ePanadol\u003c/em\u003e, \u003cem\u003eIbex and Dolimex\u003c/em\u003e tablet\u0026rsquo;s brand, respectively. It is clearly observed from these CVs that simultaneous addition of AC and CAF standard solution led to an increase of current peak. From the slopes of the regression lines (shown in inset Fig. S7) obtained by plotting current intensities versus the added amount of AC and CAF versus the electrochemical oxidation\u0026rsquo;s response, the amounts of both analyte in tablets were determined and their subsequent recovery percentage were estimated to range between 94\u0026ndash;101% and 93\u0026ndash;100% for AC and CAF respectively (see Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). These results demonstrate that the potential applicability of ZA-AcB/GCE for the determination of AC and CAF in drug samples without any interference, which is not the case when using UV spectrophotometer because AC and CAF were found to interfere (see Fig. S8).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv align=\"char\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eDetermination of AC and CAF quantities in tablets using the ZA-AcB/GCE\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eTablets brand\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eAdded (\u0026micro;M)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eFounded (\u0026micro;M)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e% recovery \u0026plusmn; %RSD\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCAF\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003ePANADOL\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e70\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e68.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e6.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e97.91\u0026thinsp;\u0026plusmn;\u0026thinsp;1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e93.88\u0026thinsp;\u0026plusmn;\u0026thinsp;5.62\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eIBEX\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e244\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17.2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e245.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e16.60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e100.76\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e96.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eDOLIMEX\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e512\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e483.27\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e26.82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e94.31\u0026thinsp;\u0026plusmn;\u0026thinsp;2.52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e99.36\u0026thinsp;\u0026plusmn;\u0026thinsp;1.95\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\"\u003e\u003csup\u003ea\u003c/sup\u003e average of three replicate measurements\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eIn this work a nanocomposite was successfully prepared by mixing a type A nanozeolite with acetylene carbon black. The physicochemical characterization of the composite shows a good interaction between both materials in which their structural integrity was maintained. The sensors prepared by coating composite film onto glassy carbon surface were found to be stable and exhibited high charge transfer kinetic and electrocatalytic toward AC thank to the synergic effect of the structural properties of nanozeolite and the electron conductivity of the carbon black. The developed sensors were successfully used to monitor the reactivity of acetaminophen and caffeine with good sensibility. Under optimum conditions, these sensors displayed large calibration curve for acetaminophen and caffeine with low detection limits. They were then successfully applied to the quantification of AC and CAF in drugs.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003eConflict of Interest\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere is no conflict to declare\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003eAcknowledgment\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFinancial support from the Royal Society ACBI programme (Grant AQ150029) is gratefully acknowledged\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRenner B, Clarke G, Grattan T, Beisel A, Mueller C, Werner U, et al. Caffeine accelerates absorption and enhances the analgesic effect of acetaminophen. The Journal of Clinical Pharmacology. 2007;47(6):715-26.\u003c/li\u003e\n\u003cli\u003eAmiri-Aref M, Raoof JB, Ojani R. A highly sensitive electrochemical sensor for simultaneous voltammetric determination of noradrenaline, acetaminophen, xanthine and caffeine based on a flavonoid nanostructured modified glassy carbon electrode. Sensors and Actuators B: Chemical. 2014;192:634-41. doi: https://doi.org/10.1016/j.snb.2013.11.006.\u003c/li\u003e\n\u003cli\u003eRoberts LI. Analgesic-antipyretic and anti-inflammatory agents and drugs employed in the treatment of gout. Goodman \u0026amp; Gilman\u0026apos;s the pharmacological basis of therapeutics. 2001.\u003c/li\u003e\n\u003cli\u003eRashwan WA. The efficacy of acetaminophen\u0026ndash;caffeine compared to ibuprofen in the control of postoperative pain after periodontal surgery: a crossover pilot study. Journal of periodontology. 2009;80(6):945-52.\u003c/li\u003e\n\u003cli\u003eAbou-Atme YS, Melis M, Zawawi KH. Efficacy and safety of acetaminophen and caffeine for the management of acute dental pain: A systematic review. 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Mediator-free simultaneous determination of acetaminophen and caffeine using a glassy carbon electrode modified with a nanotubular clay. Microchimica Acta. 2017;184(11):4485-94. doi: 10.1007/s00604-017-2483-x.\u003c/li\u003e\n\u003cli\u003eKemmegne-Mbouguen JC, Angnes L. Simultaneous quantification of ascorbic acid, uric acid and nitrite using a clay/porphyrin modified electrode. Sensors and Actuators B: Chemical. 2015;212:464-71. doi: https://doi.org/10.1016/j.snb.2015.02.046.\u003c/li\u003e\n\u003cli\u003eChitravathi S, Munichandraiah N. Voltammetric determination of paracetamol, tramadol and caffeine using poly(Nile blue) modified glassy carbon electrode. Journal of Electroanalytical Chemistry. 2016;764:93-103. doi: https://doi.org/10.1016/j.jelechem.2016.01.021.\u003c/li\u003e\n\u003cli\u003eMinh TT, Phong NH, Van Duc H, Khieu DQ. Microwave synthesis and voltammetric simultaneous determination of paracetamol and caffeine using an MOF-199-based electrode. Journal of Materials Science. 2018;53(4):2453-71.\u003c/li\u003e\n\u003cli\u003eSp\u0026atilde;taru N, Sarada BV, Tryk DA, Fujishima A. Anodic voltammetry of xanthine, theophylline, theobromine and caffeine at conductive diamond electrodes and its analytical application. Electroanalysis: An International Journal Devoted to Fundamental and Practical Aspects of Electroanalysis. 2002;14(11):721-8.\u003c/li\u003e\n\u003cli\u003eTefera M, Geto A, Tessema M, Admassie S. Simultaneous determination of caffeine and paracetamol by square wave voltammetry at poly(4-amino-3-hydroxynaphthalene sulfonic acid)-modified glassy carbon electrode. Food Chemistry. 2016;210:156-62. doi: 10.1016/j.foodchem.2016.04.106.\u003c/li\u003e\n\u003cli\u003eFeyisa TY, Kitte SA, Yenealem D, Gebretsadik G. Simultaneous electrochemical determination of paracetamol and caffeine using activated glassy carbon electrode. Anal Bioanal Electrochem. 2020;12:93-106.\u003c/li\u003e\n\u003cli\u003eMulyasuryani A, Tjahjanto RT, Andawiyah Ra. Simultaneous Voltammetric Detection of Acetaminophen and Caffeine Base on Cassava Starch\u0026mdash;Fe3O4 Nanoparticles Modified Glassy Carbon Electrode. Chemosensors. 2019;7(4):49.\u003c/li\u003e\n\u003cli\u003eMurugan E, Kumar K. Fabrication of SnS/TiO2@GO Composite Coated Glassy Carbon Electrode for Concomitant Determination of Paracetamol, Tryptophan, and Caffeine in Pharmaceutical Formulations. Analytical Chemistry. 2019;91(9):5667-76. doi: 10.1021/acs.analchem.8b05531.\u003c/li\u003e\n\u003cli\u003eXiong X-Q, Huang K-J, Xu C-X, Jin C-X, Zhai Q-G. Glassy carbon electrode modified with poly (taurine)/TiO2-graphene composite film for determination of acetaminophen and caffeine. Chemical industry and chemical engineering quarterly/CICEQ. 2013;19(3):359-68.\u003c/li\u003e\n\u003c/ol\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":"journal-of-applied-electrochemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jach","sideBox":"Learn more about [Journal of Applied Electrochemistry](http://link.springer.com/journal/10800)","snPcode":"10800","submissionUrl":"https://submission.nature.com/new-submission/10800/3","title":"Journal of Applied Electrochemistry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Acetaminophen, Caffeine, Zeolite-carbon composite, Modified electrode, Electroanalysis","lastPublishedDoi":"10.21203/rs.3.rs-3338753/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3338753/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eNanocomposite nanozeolite/acetylene black carbon was prepared by combining a type A zeolite with acetylene carbon black (AcB) and used to modify glassy carbon electrode (GCE) without polymer. The zeolite was prepared by hydrothermal method using natural kaolin. The physicochemical characterization of the composite showed a well-integrated composite in which the cubic crystal of the zeolite A and the graphitic aggregate of the carbon black were maintained. The electrochemical impedance spectroscopy study revealed that the composite film GCE (ZA-AcB/GCE) prepared by drop coating displayed a higher kinetic charge transfer compared to pristine zeolite modified GCE (ZA/GCE) and bare GCE. ZA-AcB/GCE, ZA/GCE and GCE were subsequently used to investigate the electrochemical behaviour of acetaminophen (AC) in acidic, neutral and alkaline pHs. The results demonstrate a good electrocatalytic property toward AC at composite film GCE in all these electrolytes compared to bare GCE and confirm the dependence of the electrochemical reaction mechanism of AC on the electrolyte\u0026rsquo;s pHs. Under optimal conditions, ZA-AcB/GCE exhibited higher sensitivity and selectivity toward both analytes taken individually or simultaneously within large concentration range: 0.5\u0026ndash;89 \u0026micro;M for AC and 5\u0026ndash;99 \u0026micro;M for CAF with the respective limit of detection of 0.38 and 0.82 \u0026micro;M. The developed sensors were applied successfully in the quantification of the both analytes in pharmaceutical tablets.\u003c/p\u003e","manuscriptTitle":"Polymer free Nanocomposite from Zeolite and Carbon Black as Glassy Carbon modifier platform for Simultaneous Electrochemical Quantification of Acetaminophen and Caffeine","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-09-14 17:05:24","doi":"10.21203/rs.3.rs-3338753/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2023-12-28T18:16:56+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-12-22T07:55:42+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-12-20T07:01:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"d49675e7-cf42-4f68-acf6-7b6da60c8b4b","date":"2023-12-11T05:17:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"7f22e06a-5eb3-4482-b7fe-b382af65deb0","date":"2023-12-11T02:22:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"ff1efe2e-25aa-4f03-9005-4911d67313b8_SNPRID","date":"2023-11-14T12:57:43+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"545e753e-2c80-4d16-8b19-5953f7fe70cc","date":"2023-11-14T12:16:10+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-11-02T19:28:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"500b1cd6-c683-41cb-a253-ce561124b2fc","date":"2023-10-30T04:02:12+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-10-30T03:57:31+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-09-09T21:14:55+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-09-09T10:52:32+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Applied Electrochemistry","date":"2023-09-08T21:02:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-applied-electrochemistry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jach","sideBox":"Learn more about [Journal of Applied Electrochemistry](http://link.springer.com/journal/10800)","snPcode":"10800","submissionUrl":"https://submission.nature.com/new-submission/10800/3","title":"Journal of Applied Electrochemistry","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"27ad8736-2791-4102-b52e-6a18d2375ad8","owner":[],"postedDate":"September 14th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-03-11T15:07:48+00:00","versionOfRecord":{"articleIdentity":"rs-3338753","link":"https://doi.org/10.1007/s10800-024-02076-1","journal":{"identity":"journal-of-applied-electrochemistry","isVorOnly":false,"title":"Journal of Applied Electrochemistry"},"publishedOn":"2024-03-06 15:01:25","publishedOnDateReadable":"March 6th, 2024"},"versionCreatedAt":"2023-09-14 17:05:24","video":"","vorDoi":"10.1007/s10800-024-02076-1","vorDoiUrl":"https://doi.org/10.1007/s10800-024-02076-1","workflowStages":[]},"version":"v1","identity":"rs-3338753","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3338753","identity":"rs-3338753","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}