Screen-printed electrochemical sensors for label-free potentiometric and impedimetric detection of human serum albumin

Herein, two electrochemical methods based on potentiometric and impedimetric transductions were presented for albumin targeting, employing screen-printed platforms (SPEs) to make easy and cost-effective sensors with good detection merits. The SPEs incorporated ion-to-electron multi-walled carbon nanotubes (MWCNTs) transducer. Sensors were constructed using either tridodecyl methyl-ammonium chloride (TDMACl) (sensor I) or aliquate 336S (sensor II) in plasticized polymeric matrices of carboxylated poly (vinyl chloride) (PVC-COOH). Analytical performances of the sensors were evaluated using the above-mentioned electrochemical techniques. For potentiometric assay, constructed sensors responded to albumin with −81.7 ± 1.7 (r² = 0.9986) and −146.2 ± 2.3 mV/decade (r² = 0.9991) slopes over the linearity range 1.5 μM–1.5 mM with 0.8 and 1.0 μM detection limits for respective TDMAC- and aliquate-based sensors. Interference study showed apparent selectivity for both sensors. Impedimetric assays were performed at pH = 7.5 in 10 mM PBS buffer solution with a 0.02 M [Fe(CN)₆]^−3/−4 redox-active electrolyte. Sensors achieved detection limits of 4.3 × 10⁻⁸ and 1.8 × 10⁻⁷ M over the linear ranges of 5.2×10⁻⁸–1.0×10⁻⁴ M and 1.4×10⁻⁶–1.4×10⁻³ M, with 0.09 ± 0.004 and 0.168 ± 0.009 log Ω/decade slopes for sensors based on TDMAC and aliquate, respectively. These sensors are characterized with simple construction, high sensitivity and selectivity, fast response time, single-use, and cost-effectiveness. The methods were successfully applied to albumin assessment in different biological fluids.     

Highly Selective Sensing Platform Utilizing Graphene Oxide and Multiwalled Carbon Nanotubes for the Sensitive Determination of Tramadol in the Presence of Co‐Formulated Drugs

Novel insights into the strategy of highly precise, carbon‐based electrochemical sensors are presented by exploring the excellent properties of graphene oxide (GO) and multiwalled carbon nanotube composites (GO‐MWCNTs/CPE) for the sensitive determination of tramadol hydrochloride (TRH). Cyclic voltammetry, differential pulse voltammetry, chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS) scanning electron microscopy, and X‐ray diffraction (XRD) techniques were used to characterize the properties of the sensor. The linear response obtained for TRH using the GO‐MWCNTs/CPE was found to be over the range of 2.0x10⁻⁹ to 1.1x10⁻³ M with a good linearity and high correlation (0.9996). The limits of detection and quantification were found to be 1.50x10⁻¹⁰ M and 4.99 x 10⁻¹⁰ M, respectively. The proposed sensor was applied for determination of TRH in the presence of presence of co‐formulated drugs ketorolac tromethamine (KTM) and paracetamol (PAR). The sensor was shown to successfully apply to the determination of TRH in plasma as real samples. Satisfactory recoveries of TRH from samples clearly revealed that the proposed sensor can be applied into clinical analysis, quality control and a routine determination of drugs in pharmaceutical formulations.     

Potentiometric Determination of Ciprofloxacin in Physiological Fluids Using Carbon Paste and Nano‐Composite Carbon Paste Electrodes

Nano‐composite carbon paste and simple carbon paste based potentiometric sensors were constructed and used for determination of ciprofloxacin at different pH values. Sensors were formulated utilizing graphite, suitable plasticizer, cirprofloxacinium‐phosphotungstate, as well as a highly lipophilic cation‐exchanger, sodium tetrakis(trifluoromethyl)phenyl borate. Effect of the incorporation of multi‐walled carbon nanotubes (MWCNTs) on the response characteristics of the prepared sensors was investigated. Results obtained were compared to that of a PVC‐sensor contains only the cation‐exchanger. In addition, the effect of solutions pH on the response characteristics was also studied; at pH 4.1, the slopes of bare carbon paste and MWCNTs‐based sensors were 55.7 and 66.6 mV/conc.decade in a concentration range of 10⁻²‐10⁻⁵ M with detection limits of 1.0x10⁻⁵ and 7.9x10⁻⁶ M, respectively. Although both sensors exhibited super‐Nernstian slopes at pH 2.0, the selectivity was improved compared to that measured at pH 4.1. Optimized sensors were successfully applied for the determination of ciprofloxacin in its pure form, pharmaceutical preparations, as well as spiked urine and serum samples, with high recovery.     

Novel Zn-Fe LDH/MWCNTs and Graphene/MWCNTs Nanocomposites Based Potentiometric Sensors for Benzydamine Determination in Biological Fluids and Real Water Samples

Two sensitive and selective potentiometric sensors based on zinc-iron layered double hydroxides/multiwalled carbon nanotubes (Zn−Fe LDH/MWCNTs) (sensor I) and graphene/multiwalled carbon nanotubes (Gr/MWCNTs) (sensor II) nanocomposites were developed for benzydamine hydrochloride (Benz) determination. The investigated sensors displayed excellent Nernstian slopes 58.5±0.7 and 59.5±0.5 mV decade⁻¹, detection limits 8.3×10⁻⁷ and 1.9×10⁻⁷ mol L⁻¹, long lifetimes, adequate selectivity, high chemical, and thermal stability within pH range of 2.4–8.5 for sensors І and ІІ, respectively. The surface morphology of sensors was analyzed using a Transmission Electron Microscope (TEM). The analytical method was efficiently implemented for Benz determination in biological fluids and surface water samples.     

A New Approach for Decreasing the Detection Limit of Gentamicin Ion‐selective Electrodes by Incorporation of Multiwall Carbon Nanotubes (MWCNTs)/Lipophilic Anionic Additives

Two novel carbon paste electrodes based on gentamicin‐reineckate (GNS‐RN)/multiwall carbon nanotubes (MWCNTs)/sodium tetraphenyl borate (NaTPB) or potassium tetraphenylborate (KTPB) for potentiometric determination of gentamicin sulfate were constructed. Our endeavors of lowering the detection limit for gentamicin ion‐selective electrodes were described. The paper focused on gentamicin carbon paste electrodes based on GNS‐RN as electroactive material, o ‐nitrophenyloctyl ether (o ‐NPOE) as plasticizer and incorporation of MWCNTs and lipophilic anionic additives (NaTPB and KTPB) which lower the detection limit of the electrodes showing best results for determination of gentamicin ion. The characteristics of the electrodes, GNS‐RN+NaTPB+MWCNTs (sensor 1) and GNS‐RN+KTPB+ MWCNTs (sensor 2), were measured, showing favorable features as they provided measurements of the potential with near‐Nernstian slopes of 29.6±0.3 and 29.1±0.3 mV/decade over the concentration range of 1.0×10⁻⁶–1.0×10⁻² mol L⁻¹ and pH ranges 3.0–8.2 and 3.0–8.0 in short response times (6.5 sec). Importantly, the electrodes had low detection limits of 3.0×10⁻⁷and 3.4×10⁻⁷ mol L⁻¹ for the two sensors, respectively. The sensors showed high selectivity for gentamicin ion with respect to a large number of interfering species. The electrodes were successfully applied for the potentiometric determination of GNS ions in pure state, pharmaceutical preparations and human urine with high accuracy and precision. The results of this study were compared with some previously published data using other analytical methods.     

Incorporation of Tetrazolium Blue (TB)/Gold Nanoparticles (GNPs) into Carbon Paste Electrode: Application as an Electrochemical Sensor for the Sensitive and Selective Determination of Sotalol in Micellar Medium

The electrochemical oxidation of Sotalol (SOT) based on Tetrazolium Blue (TB)/gold nanoparticles (GNPs)‐modified carbon paste electrodes (CPE) have been studied in the presence of sodium lauryl sulphate (SLS). Cyclic voltammetry (CV), differential pulse voltammetry (DPV), chronoamperometry and electrochemical impedance spectroscopy (EIS) techniques have all been utilized within this study. GNPs and TB have a synergetic effect‐giving rise to highly improved electrochemical responses and provide an advantageous platform for the basis of an electrochemical sensor with excellent performance. The experimental parameters, electrodeposition time, pH and scan rate have all been examined and optimized. The sensing of SOT via DPV is found to exhibit a wide linear dynamic range of 1.0×10⁻⁷–7.5×10⁻⁴ M in pH 2. LOD and LOQ were calculated and found to correspond to 2.5×10⁻⁸ M and 8.3×10⁻⁸ M, respectively. The suggested sensor has been used successfully for SOT determination in pharmaceutical samples and human urine as real samples. Satisfactory recoveries of analyte from these samples are demonstrated indicating that the suggested sensor is highly suitable for clinical analysis, quality control and a routine determination of SOT in pharmaceutical formulations.     

Design and application of molecularly imprinted electrochemical sensor for the new generation antidiabetic drug saxagliptin

Saxagliptin (Saxa) belongs to a new generation of antidiabetic pharmaceutical compounds used in combination with healthy diet and exercise to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). In this work, we report for the first time a molecularly imprinted polymer (MIP) based electrochemical sensor for the determination of Saxa. Computational calculations were performed, based on which five MIPs were synthesized using Saxa as a template, itaconic acid as a monomer, crosslinked with ethylene glycol dimethacrylate and Di methyl sulfoxide (DMSO) as a porogen with different ratios. Non-covalent interaction (NCI) analysis has been also conducted, and the obtained isosurface analysis was used for graphical visualization of NCI that could occur in real space as well as for the discrimination between hydrogen bond interaction, Van Der Waals attraction and spatial repulsion. The optimized polymer was incorporated as a modifier for designing an electrochemical sensor comprising MIP and Multiwalled carbon nanotubes (MwCNT) within carbon paste electrode (CPE). The operational variables including incubation time, pH, scan rate, and accumulation time were optimized. The sensor showed linearity over the concentration range (1 × 10⁻⁹–1 × 10⁻¹⁵ M) with low limit of detection (LOD) 8 × 10⁻¹⁶ and 2 × 10⁻¹⁶ M on using DPV and EIS, respectively. The sensor was successfully applied for pharmaceutical formulations, urine, and human serum samples with recovery range between 97.45–100.64 %.     

A PVC Membrane Sensor for Potentiometric Determination of Atorvastatin in Biological Samples and Pharmaceutical Preparations

The present article reports for the first time the use of Aliquat 336S‐atorvastatin as an electroactive material in a poly(vinyl chloride) matrix membrane sensor plasticized with ortho‐nitrophenyl‐octylether (o‐NPOE) or dioctylphthalate (DOP) for determination of atorvastatin in biological samples (human plasma) and in pharmaceutical preparations. The sensor shows fast, stable and reproducible response over the concentration range of 1.0×10^?7–1.0×10^?2 mol L^?1 atorvastatin with anionic slopes of 60.94±0.2 and 58.22±0.2 and pH range of 5.0–9.0 for o‐NPOE and DOP plasticized based membrane sensors, respectively. The response time of the sensor is stable and fast (10 s). Results were achieved with average recoveries of 99.5 % and 99.3 % and mean standard deviations of ±1.1 % and ±1.4 % for o‐NPOE and DOP plasticized based membrane sensors, respectively. The sensor exhibits high selectivity towards atorvastatin in the presence of many anions, drug excipients and diluents. Validation of the method according to the quality assurance standards shows suitability of the proposed sensors for use in the quality control assessment of the drug.     

Novel Potentiometric Sensors for Determination of Melatonin and Oxomemazine in Biological Samples and in Pharmaceutical Formulations

Simple, selective and accurate sensors were developed for the determination of melatonin and oxomemazine in biological samples (urine) and in pharmaceutical preparations. Potentiometric measurements were based on bismus tetraiodate‐drug ion‐pair as novel electroactive materials incorporating a plasticized PVC membrane with o‐nitrophenyl octyl ether or dioctyl phthalate. Each sensor was conditioned for at least two days in 0.1 M drug solution before use. It exhibited fast and stable Nernstian response for melatonin and oxomemazine over the concentration range of 1.0×10^?6–1.0×10^?2 M and 1.0×10^?5–1.0×10^?2 M, pH range of 3.0–6.5 and 3.5–6.0 for melatonin and oxomemazine sensors, respectively. Results with an average recovery not more than 101 % and a mean standard deviation less than 1.0 % of the nominal were obtained for the four sensors. The sensors showed reasonable selectivity towards investigated drugs in presence of many cations.     

Novel Green Potentiometric Method for the Determination of Lidocaine Hydrochloride and its Metabolite 2, 6‐Dimethylaniline; Application to Pharmaceutical Dosage Form and Milk

Sustainable chemistry has attracted the attention of scientists during the last decades owing to the great advantages encountered by its application. These include: waste reduction, energy conservation and substitution of hazardous substances with more eco‐friendly ones. Following this approach, a new sensitive and selective membrane sensor was developed and investigated for the determination of lidocaine hydrochloride (LD) and its carcinogenic metabolite 2,6‐dimethylaniline (DMA). Several polyvinyl chloride (PVC) based sensors were tried using different plasticizers as well as different cation exchangers. The best response was achieved upon using dioctylphthalate (DOP) as solvent mediator and phosphotungstate (PT) as cation exchanger. LD was selectively determined at pH 6 without interference from its carcinogenic metabolite, while DMA that had been reported to be the toxic inactive metabolite of LD secreted in the milk was determined in the milk at pH 2. Fast, stable Nernstian responses were achieved by the proposed sensors over a concentration range of 2.66×10⁻⁵ M to 1×10⁻² M for both LD and DMA. The method was validated according to the IUPAC recommendations and was successfully applied for the determination of LD in pure form and pharmaceutical dosage form, whereas DMA was successfully determined in pure form and spiked milk samples.     

A Novel Molecularly Imprinted Potentiometric Sensor for the Fast Determination of Bisoprolol Fumarate in Biological Samples

In this study, molecularly imprinted polymer (MIP) was prepared and used in the preparation of carbon paste electrode (CPE) for the quantification of bisoprolol fumarate (BF) in pure, pharmaceutical formulation and biological fluids. The selective MIP for BF was synthesized from methacrylic acid as the functional monomer, ethylene glycol dimethacrylate as the cross-linker in dimethyl sulfoxide solution, BF as the template molecule and 2, 2-azobisisobutyronitrile (AIBN) as the initiator. The non-imprinted polymer (NIP) was synthesized by the same procedure, but in the absence of the template molecule then incorporated in the paste of the carbon paste electrodes (CPEs). The prepared MIP for BF and its corresponding NIP were well characterized using scanning electron microscopy (SEM), Fourier transform infrared spectrometer, and thermal gravimetric analysis (TGA). The MIP and NIP based CPEs were further used for the determination of BF and the obtained results indicated that the sensor modified by the MIP have much higher recognition power for the BF molecules than the NIP based sensor where the MIP based CPE exhibited a Nernstian response 29.50±0.55 mV decade⁻¹ within a concentration range of 1.0×10⁻⁷–1.0×10⁻² mol L⁻¹and pH independence in the range 3.50–7.15. The proposed sensor has high selectivity over several possible interfering compounds. The obtained results by the proposed sensor were satisfactory with excellent percentage recovery and relative standard deviation and were comparable with those obtained from HPLC reported method.     

Hybrid Nanocomposite Based Graphene Sensor for Ultrasensitive Clomipramine HCl Detection

A potentiometric sensor modified with a nanocomposite of montmorillonite sheets decorated with polyaniline nanofibers (MT-PANI-NFs) as an efficient electroactive material and tricresyl phosphate (TCP) as a solvent mediator has been developed for the estimation of clomipramine HCl (CLP.HCl). The optimum potentiometric performance of the sensor was achieved by mixing of MT-PANI-NFs : TCP : graphene with a ratio of 2.69 : 30.11 : 67.20 (% wt/wt). The sensor exhibited a Nernstian slope of 59.0±0.1 mV decade⁻¹ over the concentration range of 1.0×10⁻⁵−1.0×10⁻² mol L⁻¹ with a theoretically calculated detection limit of 5.0×10⁻⁶ mol L⁻¹. The sensor performance was scrutinized in terms of several factors including thermal stability, pH effect, response time and selectivity. As, it displayed a high thermal stability at various temperature degrees (10–60 °C) with pH independency in the range of 3.5–8.5. Additionally, the developed sensor exhibited a very rapid performance for CLP.HCl detection with a fast response time of 4 s and reflecting a superior selectivity towards CLP.HCl over the other interfering species. SEM (scanning electron microscope) was used as a characteristic tool for the investigation of the proposed graphene sensor surface. Furthermore, the graphene sensor has been efficiently used for CLP.HCl estimation in its pharmaceutical formulations.     

Selective Determination of Nicorandil with a Single Planar Solid-state Potentiometric Ion Selective Electrode

Novel screen-printed electrodes (SPEs) were constructed for the quantitation of nicorandil (NIC) in its pharmaceutical formulations. Different ion-exchangers and plasticizers were investigated, but the optimal potentiometric response was obtained using nicorandil-phosphotungstate (NIC-PTA) ion associate and tricresyl phosphate as a plasticizer. A Nernstian response of 58.80±1 mV/decade was obtained over a concentration range of (1×10⁻⁶–1×10⁻²) M with 1×10⁻⁵ M as a detection limit. Sensor morphology was characterized using scanning electron microscopy (SEM). The method was validated for the assay of NIC with high selectivity, accuracy (average recovery=100.54 %), and precision (%RSD≤2).     

Fabrication of Potentiometric Sensors for the Selective Determination of Ketoconazole

Abstract

The fabrication and analytical applications of two types of potentiometric sensors for the determination of ketoconazole (KET) are described. The sensors are based on the use of KET-molybdophosphoric acid (MPA) ion pair as electroactive material. The fabricated sensors include both polymer membrane and carbon paste electrodes. Both sensors showed a linear, stable and near Nernstian slope of 57.8 mV/decade and 55.2 mV/decade for PVC membrane and carbon paste sensors respectively over a relatively wide range of KET concentration (1 × 10^?2 ? 5 × 10^?5and 1 × 10^?2 ? 1 × 10^?6). The sensors showed a fast response time of < 30 sec and < 45 sec. A useful pH range of 3–6 was obtained for both types of sensors. A detection limit of 2.96 × 10^?5M was obtained for PVC membrane sensor and 6.91 × 10^?6 M was obtained for carbon paste sensor. The proposed sensors proved to have a good selectivity for KET with respect to a large number of ions. The proposed sensors were successfully applied for the determination of KET in pharmaceutical formulations. The results obtained are in good agreement with the values obtained by the standard method.     

Molecularly Imprinted Potentiometric Sensor for Nanomolar Determination of Pioglitazone Hydrochloride in Pharmaceutical Formulations

Pioglitazone Hydrochloride (PG) is an insulin-sensitizing drug and is indicated for the treatment of type II diabetes. In this study, newly molecularly imprinted electrochemical sensors were constructed for the potentiometric determination of PG in the pharmaceutical formulations (Diabetonorm® 45 and 15 mg) with high accuracy and precision. The MIP particles (ionophore) were prepared by using the PG drug as a template, acrylamide (AC) or methacrylic acid (MAA) as a functional monomer, and ethylene glycol dimthacrylate (EGDMA) as a cross-linker. The best MIP was synthesized from AC as a functional monomer, AC-MIP. The best sensor (CPEs) was formulated from graphite (47 wt%) as a carbon source, AC-MIP (5 wt.%) as an ionophore, PMA (1 wt%) as an ion-exchanger, DNPOE (47 wt.%) as a conductive oil so-called plasticizer. The best CPE electrode exhibited response slope to the Nernstian slope of 63.0 mV Decade⁻¹, linear dynamic range of 10⁻⁸–10⁻⁴ M with the detection limit of 1.0×10⁻⁸ M, along with high reversibility, short response time 30 sec, and a long lifetime. The constructed biosensors showed high selectivity against similar interfering species (e. g. arabinose, galactose, lactose, maltose, glucose, Ba²⁺, Cu²⁺, Na⁺, Zn²⁺, Mg²⁺, Fe²⁺, Ca²⁺, NH₄⁺).     

Development of membrane electrodes for the selective determination of hyoscine butylbromide

Four polyvinyl chloride (PVC) membrane sensors for the determination of hyoscine butylbromide are described and characterized. The sensors are based on the use of the ion association complexes of hyoscine cation with ammonium reineckate counter anions as ion exchange sites in the PVC matrix. The membranes incorporate ion association complexes of hyoscine with dibutylsebathete (sensor 1), dioctylphthalate (sensor 2), nitrophenyl octyl ether (sensor 3) and β-cyclodextrin (sensor 4). The performance characteristics of these sensors were evaluated according to IUPAC recommendations, which reveal a fast, stable and linear response for hyoscine over the concentration range of 10⁻⁵-10⁻² M for sensors 1 and 2 and 10⁻⁶-10⁻² for sensors 3 and 4 with cationic slopes of −53.19, −55.17, −51.44 and −51.51 mV per concentration decade for the four sensors, respectively. The direct potentiometric determination of hyoscine butylbromide using the proposed sensors gave average recoveries % of 99.92 ± 1.11, 99.93 ± 1.00, 99.94 ± 1.18 and 99.87 ± 1.39 for the four sensors, respectively. The sensors are used for determination of hyoscine butylbromide in laboratory prepared mixtures, pharmaceutical formulations in combination with ketoprofen and in plasma. Validation of the method shows suitability of the proposed sensors for use in the quality control assessment of hyoscine butylbromide. The developed method was found to be simple, accurate and precise when compared with a reported HPLC method.     

A Novel Nanoparticles-based Electrochemical Sensing Platform for Sensitive Detection of Oral Anticoagulant; Edoxaban in Human Plasma

During COVID-19 pandemic, coagulopathy have been reported as a potential threat to most infected patients. Edoxaban (EDX) is a direct oral anticoagulant that is recently added to most COVID-19 treatment protocols either as therapy or prophylaxis. Herein, a novel nanoparticles modified glassy carbon potentiometric sensor was developed for the selective quantitation of EDX in human plasma. The electrochemical performance of the proposed sensor was assessed and compared to nanoparticle free sensor. An enhancement in electrode performance including: detection limit (3.39×10⁻⁶ mol L⁻¹), response time (8.0±2.0 s) and improved selectivity. The proposed sensor was able to determine EDX in pure form, pharmaceutical formulation and human plasma.     

Titanium Dioxide/Multi-walled Carbon Nanotubes Composite Modified Pencil Graphite Sensor for Sensitive Voltammetric Determination of Propranolol in Real Samples

A very effective electrochemical sensor for the analysis of propranolol was constructed using TiO₂/MWCNT film deposited on the pencil graphite electrode as modifier. The modified electrode represented excellent electrochemical properties such as fast response, high sensitivity and low detection limit. The proposed sensor showed an excellent selective response to propranolol in the presence of foreign species and other drugs. The electrochemical features of the modified electrode were investigated by cyclic voltammetry and electrochemical impedance spectroscopy (EIS) technique which indicated a decrease in resistance of the modified electrode versus bare PGE and MWCNT/PGE. The surface morphology for the modified electrode was determined by scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX) and Fourier transform infrared spectroscopy (FT-IR). Differential pulse technique (DPV) was used to determine propranolol which showed a good analytical response in the linear range of 8.5×10⁻⁸-6.5×10⁻⁶ M with a limit of detection 2.1×10⁻⁸ M. The TiO₂/MWCNT/PGE sensor was conveniently applied for the measurement of propranolol in biological and pharmaceutical media.     

Electrochemical reduction of ciprofloxacin at the mercury electrode and its voltammetric determination in tablet and urine

In this study a reduction square wave voltammetric method was developed and validated for the direct determination of ciprofloxacin (CIP) in pharmaceutical formulation and biological fluid using hanging mercury dropping electrode (HMDE) surface. Best results were obtained for the quantitative determination of CIP in 0.02 M Britton-Robinson buffer at pH 2.5 and at a potential of ?1300 mV vs. Ag/AgCl reference electrode. Various experimental and instrumental parameters affecting the peak current and potential of CIP electrochemical reduction were investigated and optimized. The monitored peak current was directly proportional to the concentration of CIP, where it exhibited a linear response in the range 3.0 × 10^?7–2 × 10^?6 M (r = 0.99). The accuracy of the proposed method was concluded based on the value of mean recovery of 98 ± 0.72 % with RSD of 0.181 % at a detection limit of 7 × 10^?9 M. Possible interferences by various substances usually present in pharmaceutical formulations have been also evaluated. After validating the proposed method, the applicability of this voltammetric method was demonstrated by estimating CIP in its pharmaceutical formulation and spiked human urine, where values of mean recoveries of 97 ± 1.0% and 108.0 ± 2.0% were obtained, respectively.     

A Reliable Electrochemical Sensor Based on Functionalized Magnetite Nanoparticles for Over-the-counter Allergy Medication Abuse Sensing in Biological Fluids

Diphenhydramine (DIPH) has become one of the world‘s most widely abused over-the-counter medications. In addition to relieving allergy symptoms, it is also recognized for causing elevated energy and mild euphoric effects. The U.S. Food and Drug Administration (FDA) has recently warned about serious problems at high doses including heart problems, seizures, coma or even death among addicted teenagers. Herein, a simple, cost-effective, and reliable nanocomposite based electrochemical sensor was designed for DIPH quantification in biological fluids. Introducing the functionalized Fe₃O₄ nanoparticles (NPs) into the inner-filling solution and the PVC-based ion sensing membrane has been employed and compared to the classical potentiometric approach. The nanoparticles were incorporated to endorse in situ cooperative ion-pairing interaction between the ionophore and DIPH, and to improve the selectivity and detection limit (9.5×10⁻⁸ M). Nernstian potentiometric response was achieved for DIPH over the concentration range of 1.0×10⁻⁷ to 1.0×10⁻² M with a slope of 59.0±0.2 mV/decade. Inherent merits of the proposed sensor include fast response time (6 s), superior stability (60 days) with higher sensitivity and selectivity towards DIPH without interference from co-formulated drugs and several ions commonly found in biological matrices. The proposed sensor was successfully applied to the potentiometric determination of DIPH in different biological fluids (plasma and human milk) with an average recovery of 99.06±1.95 % and 100.34±1.92 %, respectively. As a consequence, the developed ISE might be the ideal choice for in-line DIPH measurements in plasma samples to identify overdose ingestion and its related symptoms, as well as for quality-control laboratories without prior treatments.