Polymeric membrane potentiometric antibiotic sensors using computer-aided screening of supramolecular macrocyclic carriers.

Carrier-based polymeric membrane potentiometric sensors are an ideal tool for detecting ionic species. However, in the fabrication of these sensors, the screening of carriers still relies on empirical trial- and error-based optimization, which requires tedious and time-consuming experimental verification. In this work, computer-aided screening of carriers is applied in the preparation of polymeric membrane potentiometric sensors. Molecular docking is used to study the host-guest interactions between receptors and targets. Binding energies are employed as the standard to screen the appropriate carrier. As a proof-of-concept experiment, the antibiotic ciprofloxacin is selected as the target model. A series of supramolecular macrocyclic receptors including cyclodextrins, cucurbiturils and calixarenes are chosen as potential receptors. The proposed sensor based on the receptor calix[4]arene screened by molecular docking shows a lower detection limit of 0.5 µmol L-1 for ciprofloxacin. It can be expected that the proposed computer-aided screening technique of carriers can provide a simple but highly efficient method for the fabrication of carrier-based electrochemical and optical sensors.

Non-enzymatic paper-based analytical device for direct potentiometric detection of urine creatinine.

A paper-based analytical device (PAD) with an integrated composite electrode has been designed and fabricated for non-enzymatic creatinine sensing. Reduced graphene oxide (rGO) was employed to modify the PAD so that it could function as a solid-contact transducer. A new macrocyclic pyrido-hexapeptide derivative was made and used as a special ionophore in the creatinine membrane sensor. The synthesized PAD showed a detection limit of 1.0 µM (S/N = 3) and a potentiometric response towards creatinine throughout a log-linear range of 2.0 µM-10 mM (R2 = 0.9998). The sensor shows significant selectivity for a few related substances, including ephedrine, codeine, ketamine, caffeine, urea, urate, carbinoxamine, and dextromethorphan. It has been established that the testing method is appropriate for the direct potentiometric detection of creatinine in a variety of human urine sample types. When an indicating electrode and a reference electrode are put on the same flexible disposable, this lets applications with a small sample volume be done. For point-of-care creatinine measurement, the developed paper-based analytical equipment is a good choice because it is affordable, easily accessible, and self-pumping (especially when combined with potentiometric detection).

Label-free and highly-sensitive detection of calcium ions using a silicon-on-sapphire light-addressable potentiometric sensor.

BACKGROUND: Ionic calcium (Ca2+) plays a crucial role in maintaining normal physiological and biochemical functions within the human body. Detecting the concentration of Ca2+ is of utmost significance for various purposes, including disease screening, cellular metabolism research, and evaluating drug effectiveness. However, current detection approaches such as fluorescence and colorimetry face limitations due to complex labeling techniques and the inability to track changes in Ca2+ concentration. In recent years, extensive research has been conducted in this field to explore label-free and efficient approaches. RESULTS: In this study, a novel light-addressed potentiometric sensor (LAPS) using silicon-on-sapphire technology, has been successfully developed for Ca2+ sensing. The Ca2+-sensitive LAPS achieved a wide-range detection of Ca2+, ranging from 10-2 M to 10-7 M, with an impressive detection limit of 100 nM. These advancements are attributed to the ultra-thin silicon layer, silicon dioxide layer, and solid-state silicon rubber sensitive membrane around 6 µm. Furthermore, the sensor demonstrated the ability to dynamically monitor fluctuations in Ca2+ concentration ranging from 10-9 M to 10-2 M within a solution. Its remarkable selectivity, specificity, and long-term stability have facilitated its successful application in the detection of Ca2+ in human serum and urine. SIGNIFICANCE AND NOVELTY: This work presents a Ca2+-sensitive sensor that combines a low detection limit and a wide detection range. The development represents the emergence of a label-free and rapid Ca2+ detection tool with immense prospects in home-based health monitoring, community disease screening, as well as cellular metabolism, and drug screening evaluations.

Enzymatic Galvanic Redox Potentiometry for In Vivo Biosensing.

Redox potentiometry has emerged as a new platform for in vivo sensing, with improved neuronal compatibility and strong tolerance against sensitivity variation caused by protein fouling. Although enzymes show great possibilities in the fabrication of selective redox potentiometry, the fabrication of an enzyme electrode to output open-circuit voltage (EOC) with fast response remains challenging. Herein, we report a concept of novel enzymatic galvanic redox potentiometry (GRP) with improved time response coupling the merits of the high selectivity of enzyme electrodes with the excellent biocompatibility and reliability of GRP sensors. With a glucose biosensor as an illustration, we use flavin adenine dinucleotide-dependent glucose dehydrogenase as the recognition element and carbon black as the potential relay station to improve the response time. We find that the enzymatic GRP biosensor rapidly responds to glucose with a good linear relationship between EOC and the logarithm of glucose concentration within a range from 100 µM to 2.65 mM. The GRP biosensor shows high selectivity over O2 and coexisting neurochemicals, good reversibility, and sensitivity and can in vivo monitor glucose dynamics in rat brain. We believe that this study will pave a new platform for the in vivo potentiometric biosensing of chemical events with high reliability.

A Potentiometric Dual-Channel Microsensor Reveals that Fluctuation of H2 S is Less pH-Dependent During Spreading Depolarization in the Rat Brain.

Spreading depolarization (SD) is one of the most common neuropathologic phenomena in the nervous system, relating to numerous diseases. However, real-time monitoring the rapid chemical changes during SD to probe the molecular mechanism remains a great challenge. We develop a potentiometric dual-channel microsensor for simultaneous monitoring of H2 S and pH featuring excellent selectivity and spatiotemporal resolution. Using this microsensor we first observe real time changes of H2 S and pH in the rat brain induced by SD. This changes of H2 S are completely suppressed when the rat pre-treats with aminooxyacetic acid (AOAA), a blocker to inhibit the H2 S-producing enzyme, indicating H2 S fluctuation might be related to enzyme-dependent pathway during SD and less pH-dependent. This study provides a new perspective for studying the function of H2 S and the molecular basis of SD-associated diseases.

Potentiometric detection of apomorphine in human plasma using a 3D printed sensor.

Apomorphine is a dopamine agonist that is used for the management of Parkinson's disease and has been proven to effectively decrease the off-time duration, where the symptoms recur, in Parkinson's disease patients. This paper describes the design and fabrication of the first potentiometric sensor for the determination of apomorphine in bulk and human plasma samples. The fabrication protocol involves stereolithographic 3D printing, which is a unique tool for the rapid fabrication of low-cost sensors. The solid-contact apomorphine ion-selective electrode combines a carbon-mesh/thermoplastic composite as the ion-to-electron transducer and a 3D printed ion-selective membrane, doped with the ionophore calix[6]arene. The sensor selectively measures apomorphine in the presence of other biologically present cations - sodium, potassium, magnesium, and calcium - as well as the commonly prescribed Parkinson's pharmaceutical, levodopa (L-Dopa). The sensor demonstrated a linear, Nernstian response, with a slope of 58.8 mV/decade over the range of 5.0 mM-9.8 µM, which covers the biologically (and pharmaceutically) relevant ranges, with a limit of detection of 2.51 µM. Moreover, the apomorphine sensor exhibited good stability (minimal drift of just 188 µV/hour over 10 h) and a shelf-life of almost 4 weeks. Experiments performed in the presence of albumin, the main plasma protein to which apomorphine binds, demonstrate that the sensor responds selectively to free-apomorphine (i.e., not bound or complexed forms). The utility of the sensor was confirmed through the successful determination of apomorphine in spiked human plasma samples.

A Novel Polymeric Membrane Sensor for Chlorhexidine Determination.

In the present work, potentiometric sensors with polymer membranes used for chlorhexidine (CHXD) determination were developed. The polymer membranes were plasticized with bis(2-ethylheksyl)sebacate (DOS) or 2-nitrophenyloctyl ether (o-NPOE). The active compounds used in the membrane were cyclodextrins, crown ethers, and ion exchangers. The best-constructed electrode was based on neutral heptakis(2,3,6-tri-O-benzoyl)-ß-cyclodextrin with lipophilic salt (KTpClBP)-potassium tetrakis(4-chlorophenyl) borate-dissolved in plasticizer, DOS. The presented electrode is characterized by an average cationic slope of 30.9 ± 2.9 mV decade-1 within a linear range of 1 × 10-6 to 1 × 10-3 mol × L-1, while the value of the correlation coefficient is 0.9970 ± 0.0026. The response time was about 5 s when increasing the sample concentration and about 10 s when diluting the sample. The electrode potential is independent of the pH within a range of 4.0-9.5. The polymeric membrane sensor was successfully applied for assays of chlorhexidine digluconate in pure samples and pharmaceutical samples. The relative error from three replicate measurements was determined to be 1.1%. and the accuracy was RSD = 0.3-1.1%.

A comparative study of green solid contact ion selective electrodes for the potentiometric determination of Letrozole in dosage form and human plasma.

Analysis of drugs clinically and their identification in biological samples are of utmost importance in the process of therapeutic drug monitoring, also in pharmacokinetic investigations and tracking of illicit medications. These investigations are carried out using a variety of analytical methods, including potentiometric electrodes. Potentiometric electrodes are a wonderful solution for researchers because they outperform other methods in terms of sustainability, greenness, and cost effectiveness. In the current study, ion-selective potentiometric sensors were assembled for the aim of quantification of the anticancer drug Letrozole (LTZ). The first step was fabrication of a conventional sensor based on the formation of stable host-guest inclusion complex between the cationic drug and 4-tert-butylcalix-8-arene (TBCAX-8). Two additional sensors were prepared through membrane modification with graphene nanocomposite (GNC) and polyaniline (PANI) nanoparticles. Linear responses of 1.00 × 10-5-1.00 × 10-2, 1.00 × 10-6-1.00 × 10-2 and 1.00 × 10-8-1.00 × 10-3 with sub-Nernstian slopes of 19.90, 20.10 and 20.30 mV/decade were obtained for TBCAX-8, GNC, and PANI sensors; respectively. The developed sensors were successful in determining the drug LTZ in bulk powder and dosage form. PANI modified sensor was used to determine LTZ in human plasma with recoveries ranging from 88.00 to 96.30%. IUPAC recommendations were followed during the evaluation of the electrical performance of the developed sensors. Experimental conditions as temperature and pH were studied and optimized. Analytical Eco-scale and Analytical GREEness metric were adopted as the method greenness assessment tools.

Ionophore-Based Polymeric Sensors for Potentiometric Assay of the Anticancer Drug Gemcitabine in Pharmaceutical Formulation: A Comparative Study.

Gemcitabine is a chemotherapeutic agent used to treat various malignancies, including breast and bladder cancer. In the current study, three innovative selective gemcitabine hydrochloride sensors are developed using 4-tert-butylcalix-[8]-arene (sensor 1), ß-cyclodextrin (sensor 2), and γ-cyclodextrin (sensor 3) as ionophores. The three sensors were prepared by incorporating the ionophores with o-nitrophenyl octyl ether as plasticizer and potassium tetrakis(4-chlorophenyl) borate as ionic additive into a polyvinyl chloride polymer matrix. These sensors are considered environmentally friendly systems in the analytical research. The linear responses of gemcitabine hydrochloride were in the concentration range of 6.0 × 10-6 to 1.0 × 10-2 mol L-1 and 9.0 × 10-6 to 1.0 × 10-2 mol L-1 and 8.0 × 10-6 to 1.0 × 10-2 mol L-1 for sensors 1, 2, and 3, respectively. Over the pH range of 6-9, fast-Nernst slopes of 52 ± 0.6, 56 ± 0.3, and 55 ± 0.8 mV/decade were found in the same order with correlation regressions of 0.998, 0.999, and 0.998, respectively. The lower limits of detection for the prepared sensors were 2.5 × 10-6, 2.2 × 10-6, and 2.7 × 10-6 mol L-1. The sensors showed high selectivity and sensitivity for gemcitabine. Validation of the sensors was carried out in accordance with the requirements established by the IUPAC, while being inexpensive and easy to use in drug formulation. A statistical analysis of the methods in comparison with the official method showed that there was no significant difference in accuracy or precision between them. It was shown that the new sensors could selectively and accurately find gemcitabine hydrochloride in bulk powder, pharmaceutical formulations, and quality control tests. The ionophore-based sensor shows several advantages over conventional PVC membrane sensor sensors regrading the lower limit of detection, and higher selectivity towards the target ion.

Diazotization titrations in pharmacopoeial quality control of medicines and proposals for their revision in the European Pharmacopoeia.

Based on the data in the Ph. Eur., some other newer pharmacopoeias and published experimental papers propose to revise the text of Ph. Eur. 2.5.8. First, it is necessary to specify which of the electrometric methods should be used to indicate the endpoint of diazotization titrations in Ph. Eur. (preferable potentiometry with a platinum indicating electrode). The amount of potassium bromide in the titration solution may be reduced to 1 g, the cooling of the solution before titration may be omitted from the framework procedure, and it may be specified in individual monographs if necessary to obtain accurate and correct results for some medicines. Diazotization titration can be performed in Ph. Eur. and can also be used to determine the content of some other medicines.

Methods gold standard in clinic millifluidics multiplexed extended gate field-effect transistor biosensor with gold nanoantennae as signal amplifiers.

We present a portable multiplexed biosensor platform based on the extended gate field-effect transistor and demonstrate its amplified response thanks to gold nanoparticle-based bioconjugates introduced as a part of the immunoassay. The platform comprises a disposable chip hosting an array of 32 extended gate electrodes, a readout module based on a single transistor operating in constant charge mode, and a multiplexer to scan sensing electrodes one-by-one. Although employing only off-the-shelf electronic components, our platform achieves sensitivities comparable to fully customized nanofabricated potentiometric sensors. In particular, it reaches a detection limit of 0.2 fM for the pure molecular assay when sensing horseradish peroxidase-linked secondary antibody (∼0.4 nM reached by standard microplate methods). Furthermore, with the gold nanoparticle bioconjugation format, we demonstrate ca. 5-fold amplification of the potentiometric response compared to a pure molecular assay, at the detection limit of 13.3 fM. Finally, we elaborate on the mechanism of this amplification and propose that nanoparticle-mediated disruption of the diffusion barrier layer is the main contributor to the potentiometric signal enhancement. These results show the great potential of our portable, sensitive, and cost-efficient biosensor for multidimensional diagnostics in the clinical and laboratory settings, including e.g., serological tests or pathogen screening.

Near-Infrared Laser Irradiation-Modulated High-Temperature Solid-Contact Ion-Selective Electrodes: Potentiometric Detection of Ca2+ in Seawater.

The high-temperature potentiometry operated by nonisothermal heating is a promising way to break through the traditional potentiometric responses of ion-selective electrodes (ISEs) at room temperature. Herein, a locally heated strategy through near-infrared region (NIR) laser irradiation upon the photothermal mesoporous carbon material placed between the ion-selective membrane and the glassy carbon substrate is introduced to obtain the high-temperature potentiometric performance of a solid-contact Ca2+-ISE for detection of Ca2+ in seawater. Based on the light-to-heat conversion of the mesoporous carbon-based solid contact, the temperature of the solid-contact Ca2+-ISE upon continuous NIR laser irradiation can be increased from room temperature to 60-70 °C, and the slope of the electrode is promoted up to about 30% according to the thermodynamic steady-state potentiometric response. The pulsed potentiometric response of the solid-contact Ca2+-ISE upon a pulsed NIR laser irradiation of 5 s also shows a linear change as a function of Ca2+ activities, and the improved slope from 27.1 ± 0.6 to 38.1 ± 0.9 mV/dec can be obtained under dual control of the temperature of the electrode and the transient current induced by the pulsed NIR laser irradiation. As compared to the traditional potentiometric measurement under zero-current conditions at room temperature, the NIR laser-modulated high-temperature potentiometric response provides an alternative way for measurement of the solid-contact ISEs.

Portable Device for Potentiometric Determination of Antioxidant Capacity.

For the first time, a prototype of a portable device for the potentiometric determination of antioxidant capacity based on a new measurement principle is proposed. A feature of the approach is the use of an electrochemical microcell with separated spaces and two identical electrodes with immobilized reagents. An antioxidant solution is introduced into one half-cell, and the antioxidants interact with the reagents. The other half-cell contains only reagents. The potential difference between the electrodes is due to the change in the ratio of the oxidized and reduced form of the reagents, which occurs as a result of the reaction with the antioxidants in one of the half-cells and is related to their concentration. The range of linearity of the microcell with immobilized reagents is 40-4000 µM-eq, and the limit of detection is 20 µM-eq. The device was successfully tested in the analysis of standard antioxidant solutions. The recoveries were (92-113)%, and the relative standard deviation did not exceed 15%. A good correlation was found between the data obtained by the approach and the potentiometric method in a macrocell for fruit juice analysis. Pearson's coefficient for the obtained experimental data was 0.9955. The proposed portable device is promising and can be used in field conditions.

Fabrication and Applications of Potentiometric Membrane Sensors Based on Specific Recognition Sites for the Measurement of the Quinolone Antibacterial Drug Gemifloxacin.

Supramolecular gemifloxacin (GF) sensors have been developed. Supramolecular chemistry is primarily concerned with noncovalent intermolecular and intramolecular interactions, which are far weaker than covalent connections, but they can be exploited to develop sensors with remarkable affinity for a target analyte. In order to determine the dose form of the quinolone antibacterial drug gemifloxacin, the current study's goal is to adapt three polyvinylchloride (PVC) membrane sensors into an electrochemical technique. Three new potentiometric membrane sensors with cylindric form and responsive to gemifloxacin (GF) were developed. The sensors' setup is based on the usage of o-nitrophenyl octyl ether (o-NPOE) as a plasticizer in a PVC matrix, ß-cyclodextrin (ß-CD) (sensor 1), γ-cyclodextrin (γ-CD) (sensor 2), and 4-tert-butylcalix[8]arene (calixarene) (sensor 3) as an ionophore, potassium tetrakis (4-chlorophenyl) borate (KTpClPB) as an ion additive for determination of GF. The developed method was verified according to IUPAC guidelines. The sensors under examination have good selectivity for GF, according to their selectivity coefficients. The constructed sensors demonstrated a significant response towards to GF over a concentration range of 2.4 × 10-6, 2.7 × 10-6, and 2.42 × 10-6 mol L-1 for sensors 1, 2, and 3, respectively. The sensors showed near-Nernstian cationic response for GF at 55 mV, 56 mV, and 60 mV per decade for sensors 1, 2, and 3, respectively. Good recovery and relative standard deviations during the day and between days are displayed by the sensors. They demonstrated good stability, quick response times, long lives, rapid recovery, and precision while also exhibiting good selectivity for GF in various matrices. To determine GF in bulk and dose form, the developed sensors have been successfully deployed. The sensors were also employed as end-point indicators for titrating GF with sodium tetraphenyl borate.

Ion-Selective Electrodes with Solid Contact Based on Composite Materials: A Review.

Potentiometric sensors are the largest and most commonly used group of electrochemical sensors. Among them, ion-selective electrodes hold a prominent place. Since the end of the last century, their re-development has been observed, which is a consequence of the introduction of solid contact constructions, i.e., electrodes without an internal electrolyte solution. Research carried out in the field of potentiometric sensors primarily focuses on developing new variants of solid contact in order to obtain devices with better analytical parameters, and at the same time cheaper and easier to use, which has been made possible thanks to the achievements of material engineering. This paper presents an overview of new materials used as a solid contact in ion-selective electrodes over the past several years. These are primarily composite and hybrid materials that are a combination of carbon nanomaterials and polymers, as well as those obtained from carbon and polymer nanomaterials in combination with others, such as metal nanoparticles, metal oxides, ionic liquids and many others. Composite materials often have better mechanical, thermal, electrical, optical and chemical properties than the original components. With regard to their use in the construction of ion-selective electrodes, it is particularly important to increase the capacitance and surface area of the material, which makes them more effective in the process of charge transfer between the polymer membrane and the substrate material. This allows to obtain sensors with better analytical and operational parameters. Brief characteristics of electrodes with solid contact, their advantages and disadvantages, as well as research methods used to assess their parameters and analytical usefulness were presented. The work was divided into chapters according to the type of composite material, while the data in the table were arranged according to the type of ion. Selected basic analytical parameters of the obtained electrodes have been collected and summarized in order to better illustrate and compare the achievements that have been described till now in this field of analytical chemistry, which is potentiometry. This comprehensive review is a compendium of knowledge in the research area of functional composite materials and state-of-the-art SC-ISE construction technologies.

Potentiometric-Type Gas Sensor Using MgFe2O4 Sensing Electrode for Detection of Hydrocarbon Based on Carbon Number.

Hydrocarbon (HC) monitoring is necessary for safe and effective operations in industries such as petroleum and gas. In this study, total hydrocarbons can be detected by using yttria-stabilized zirconia (YSZ)-based potentiometric-type gas sensor using MgFe2O4 sensing electrode (SE). The sensor was found to generate a similar response magnitude to those of hydrocarbons that have the same carbon number, irrespective of the type of carbon bond (total hydrocarbon detection). Aside from being capable of detecting total hydrocarbons sensitively and selectively with rapid response time, the sensor using MgFe2O4-SE also exhibited a linear relationship between sensor responses and carbon number. In addition to that, the developed sensor showed a logarithmically linear relationship between sensor responses and HC concentration in the range 20-700 ppm. These sensing characteristics were confirmed to be reproducible, and sensor responses toward HC were found to be repeatable and gradually decreased with increasing in O2 concentration in the range of 3-21 vol %.

A trimodal detection paper chip for undisclosed drug "sibutramine" in nutraceuticals.

Nutraceuticals are promoted and marketed with the stated label of being natural as well as safe herbal products. In order to enhance their effectiveness, nutraceuticals are usually adulterated with undeclared constituents. Slimming herbs may contain sibutramine (SBT) which is an FDA-banned ingredient due to its fatal outcomes. This current work's aim is to design a trimodal sensor for SBT detection in different herbal slimming formulations. Screen-printed silver and multi-walled carbon nanotube inks were employed for the potentiometric sensor. The sensor was designed to fill a reaction well in which a carbon dot-silver nanoparticle pair was applied for fluorimetric and colorimetric purposes. The trimodal sensor was designed to fit an 8 mm 2-pin LED strip connector. Potentiometric measurement took place upon application of one sample aliquot then the optical reaction proceeded next in a specified zone for optical detection. These multiple detection mechanisms achieved the required selectivity for SBT determination in the presence of other slimming products' additives. This trimodal sensor satisfied World Health Organization standards for point-of-care devices demonstrating the suggested device as a dynamic part for rapid on-site detection of undisclosed SBT.

In Situ Drift Monitoring and Calibration of Field-Deployed Potentiometric Sensors Using Temperature Supervision.

Potentiometric ion-selective electrodes (ISEs) have broad applications in personalized healthcare, smart agriculture, oil/gas exploration, and environmental monitoring. However, high-precision potentiometric sensing is difficult with field-deployed sensors due to time-dependent voltage drift and the need for frequent calibration. In the laboratory setting, these issues are resolved by repeated calibration by measuring the voltage response at multiple standard solutions at a constant temperature. For field-deployed sensors, it is difficult to frequently interrupt operation and recalibrate with standard solutions. Moreover, the constant surrounding temperature constraint imposed by the traditional calibration process makes it unsuitable for temperature-varying field use. To address the challenges of traditional calibration for field-deployed sensors, in this study, we propose a novel in situ calibration approach in which we use natural/external temperature variation in the field to obtain the time-varying calibration parameters, without having to relocate the sensors or use any complex system. We also develop a temperature-supervised monitoring method to detect the drift of the sensor during operation. Collectively, the temperature-based drift monitoring and in situ calibration methods allow us to monitor the drift of sensors and correct them periodically to achieve high-precision sensing. We demonstrate our approach in three testbeds: (1) under controlled temperature variation in the lab, (2) under natural temperature variation in a greenhouse, and (3) in the field to monitor nitrate activity of an agricultural site. In the laboratory study, we validate that the calibration parameters of printed nitrate ISEs can be reproduced by our proposed calibration process; therefore, it can serve as an alternative to traditional calibration processes. In the greenhouse, we show the use of natural temperature variation to calibrate the sensors and detect the drift in a fixed concentration nitrate solution. Finally, we demonstrate the use of the method to monitor the nitrate activity of an agricultural field within 10% of laboratory-based measurements (i.e., a sensitivity of 0.03 mM) for a period of 22 days. The findings highlight the prospect of temperature-based calibration and drift monitoring for high-precision sensing with field-deployed ISEs.

An Analytical Method for Determination of Total Iron in Pharmaceuticalgrade Intravenous Iron Colloidal Complexes by Redox-Potentiometry.

BACKGROUND: Iron carbohydrate complexes are colloidal dispersions made up of polynuclear Fe(III)-oxyhydroxide cores surrounded by a carbohydrate shell that stabilizes the complex in iron colloidal formulations. The current study provides an improved method that is precise, accurate, and linear for quantifying total iron in most Iron Carbohydrate Colloid Drug Products. METHODS: Redox iodometry with a potentiometric determination is used to evaluate total iron in intravenous formulations. The visual indicator approach is more prone to fluctuations at endpoint calculations. Hence, the voltage potential approach is widely accepted as it is more accurate and sensitive. It tracks the actual change in activity that coincides with the equivalence point that is finally considered an endpoint. The principle is based on the idea that ferric iron in formulation reduces to ferrous iron in the presence of the iodide, which oxidizes to iodine. The released iodine is titrated using sodium thiosulfate. RESULTS: The proposed method was precise, with %RSD (relative standard deviation) not more than 1. The method was linear between 80% and 120%, with a linear regression of 0.999. The percent recovery ranged from 98.20 to 99.98 for the concentration ranges of 80-120. The method's robustness was checked by various analysts using different reagent grades. CONCLUSION: The proposed potentiometric determination method was precise, accurate, linear, and sensitive. The method was successfully validated, and the total iron content determined for commercial batches agrees with the iron claim on the label. Therefore, this method can be adapted widely for total iron content determination in any Intravenous formulation currently available on the market. The proposed method is more accessible at the Quality Control facilities on an industrial scale.

Stability Enhancement of Galvanic Redox Potentiometry by Optimizing the Redox Couple in Counterpart Poles.

Potentiometry based on the galvanic cell mechanism, i.e., galvanic redox potentiometry (GRP), has recently emerged as a new tool for in vivo neurochemical sensing with high neuronal compatibility and good sensing property. However, the stability of open circuit voltage (EOC) outputting remains to be further improved for in vivo sensing application. In this study, we find that the EOC stability could be enhanced by adjusting the sort and the concentration ratio of the redox couple in the counterpart pole (i.e., indicating electrode) of GRP. With dopamine (DA) as the sensing target, we construct a spontaneously powered single-electrode-based GRP sensor (GRP2.0) and investigate the correlation between the stability and the redox couple used in the counterpart pole. Theoretical consideration suggests that the EOC drift is minimum when the concentration ratio of the oxidized form (O1) to the reduced form (R1) of the redox species in the backfilled solution is 1:1. The experimental results demonstrate that, compared with other redox species (i.e., dissolved O2 at 3 M KCl, potassium ferricyanide (K3Fe(CN)6), and hexaammineruthenium(III) chloride (Ru(NH3)6Cl3)) used as the counterpart pole, potassium hexachloroiridate(IV) (K2IrCl6) exhibits better chemical stability and outputs more stable EOC. As a result, when IrCl62-/3- with the concentration ratio of 1:1 is used as the counterpart, GRP2.0 displays not only an excellent EOC stability (i.e., 3.8 mV drifting during 2200 s for in vivo recording) but also small electrode-to-electrode variation (i.e., the maximum EOC variation between four electrodes is 2.7 mV). Upon integration with the electrophysiology, GRP2.0 records a robust DA release, accompanied by a burst of neural firing, during the optical stimulation. This study paves a new avenue to stable neurochemical sensing in vivo.