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.     

Construction and Performance Characterization of Ion‐Selective Electrodes for Potentiometric Determination of Paroxetine Hydrochloride in Pharmaceutical Preparations and Biological Fluids

Three types of ion‐selective electrodes: PVC membrane, modified carbon paste (CPE), and coated graphite electrodes (CGE) have been constructed for determining paroxetine hydrochloride (Prx). The electrodes are based on the ion pair of paroxetine with sodium tetraphenylborate (NaTPB) using dibutyl phthalate as plasticizing solvent. Fast, stable and potentiometric response was obtained over the concentration range of 1.1×10^?5–1×10^?2 mol L^?1 with low detection limit of 6.9×10^?6 mol L^?1 and slope of a 56.7±0.3mV decade^?1 for PVC membrane electrode, the concentration range of 2×10^?5–1×10^?2 mol L^?1 with low detection limit of 1.2×10^?5 mol L^?1 and slope of a 57.7±0.6 mV decade^?1 for CPE, and the concentration range of 2×10^?5–1×10^?2 mol L^?1 with low detection limit of 8.9×10^?6 mol L^?1 and slope of a 56.1±0.1 mV decade^?1 for CGE. The proposed electrodes display good selectivity for paroxetine with respect to a number of common inorganic and organic species. The electrodes were successfully applied to the potentiometric determination of paroxetine hydrochloride in its pure state, its pharmaceutical preparation, human urine and plasma.     

Development of a New Coated Graphite Phenylephrine Potentiometric Sensor and Its Applications to Pharmaceutical and Biological Analysis

The construction and performance characteristics of a coated graphite phenylephrine‐selective electrode based on incorporation of the ion‐association complex of phenylephrine‐tetraphenylborate in plasticized PVC matrix was studied. The electrode exhibited a Nernstian slope of 59.0 mV/decade to phenylephrine over a wide concentration range from 3.0×10^?6 to 5.6×10^?2 M with a low detection limit of 1.5×10^?6 M. The proposed electrode manifested advantages of fast response, long life time and, most important, good selectivities for phenylephrine relative to a wide variety of common foreign inorganic cations, anions and also organic species. The electrode was successfully applied to determine phenylephrine in adult cold tablets, phenylephrine eye‐drops and also blood serum samples. The inclusion complex formation between α‐ and β‐cyclodextrine and phenylephrine was studied potentiometrically by the proposed electrode.     

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).     

A New Validated Potentiometric Method for Batch and Continuous Quality Control Monitoring of Oseltamivir Phosphate (Taminil) in Drug Formulations and Biological Fluids

A new validated potentiometric method is described for batch and continuous quality control monitoring of the drug oseltamivir phosphate (Taminil) (OST). The method involves the development of a potentiometric sensor responsive to the drug based on the use of the ion‐association complex of (OST⁺) cation with phosphomolybdate anion (PMA^?) as an electroactive material in a poly(vinyl chloride) matrix membrane plasticized with o‐nitrophenyloctyl ether (o‐NPOE). Optimization of the performance characteristics of the sensor is described. A membrane incorporating the OST‐PMA‐NPOE complex in a tubular flow through detector is used in a two channel flow injection set up for continuous monitoring of the drug at a frequency of ～30 samples h^?1. The sensor shows fast near‐Nernstian response for OST over the concentration range 5.2×10^?5–0.8×10^?2 M (21.34 µg mL^?1–3.23 mg mL^?1) with a detection limit of 9.1×10^?6 M (3.73 µg mL^?1) over the pH range 4.6–6.1. The sensor displays good selectivity for OST drug over some basic drugs, inorganic cations, excipients and diluents commonly used in the drug formulations. Validation of the assay method is tested by measuring the lower detection limit, range, linearity, bias, trueness, accuracy, precision, and between‐day‐variability, within day reproducibility, selectivity and ruggedness (robustness). The results reveal good potentiometric performance of the proposed sensor for determination of OST in pharmaceutical capsules and in biological fluid matrices as well as for testing the dissolution profile of the drug and drug homogeneity.     

Application of Precipitation-based and Nanoparticle-based Techniques for Fabrication of Potentiometric Sensors for Nano Molar Determination of Chitosan and Polyvinyl Pyrrolidone in Pharmaceutical Formulations and Biological Fluids

Chitosan (CH) is one of the most abundant biopolymers with multiple applications. Polyvinyl pyrrolidone (PVP) has specific binding and detoxification properties that are of great interest in health care. Hence, it arises a crucial urge to develop economic sensors to analyze CH and PVP in pharmaceutical formulations and biological samples. Two portable sensors were fabricated using precipitation-based technique, and nanoparticles-based technique, for determination of CH and PVP in sensor 1 and 2; respectively. Linear responses of 10⁻⁵ to10⁻⁷ M and 10⁻² to10⁻⁷ M at pH 3.6–4.8 and 7.2–8.4, with ideal Nernstian slopes of 60.00 and 59.83 mV /decade, and nanomolar LODs of 94.90 and 81.20 nM were observed for CH and PVP; respectively. The percentage recoveries were 100.40±1.03 and 100.19±0.64 for sensors 1 and 2; respectively. Both sensors were successfully applied in biological fluids without pre-treatment. Accurate results were obtained using sensor 1, in pure form, pharmaceutical formulations, human plasma, rat liver and rat brain, as well as sensor 2, in pure form, pharmaceutical formulations and urine samples. The results were statistically compared with the reported methods and no significant difference was observed.     

Construction and Validation of New Electrochemical Carbon Nanotubes Sensors for Determination of Acebutolol Hydrochloride in Pharmaceuticals and Biological Fluids

A simple, rapid and a highly selective method for direct electrochemical determination of acebutolol hydrochloride (AC) was developed. The developed method was based on the construction of three types of sensors conventional polymer (I), carbon paste (II) and modified carbon nanotubes (MCNTs) carbon paste (III). The fabricated sensors depend mainly on the incorporation of acebutolol hydrochloride with phosphotungstic acid (PTA) forming ion exchange acebutolol‐phosphotungstate (AC‐PT). The performance characteristics of the proposed sensors were studied. The sensors exhibited Nernstian responses (55.6 ± 0.5, 57.14 ± 0.2 and 58.6 ± 0.4 mV mol L^?1) at 25 °C over drug concentration ranges (1.0 × 10^?6‐1.0 × 10^?2, 1.0 × 10^?7‐1.0 × 10^?2 and 5.0 × 10^?8‐1.0 × 10^?2 mol L^?1 with lower detection limits of (5.0 × 10^?7, 5.0 × 10^?8 and 2.5 × 10^?8 mol L^?1 for sensors (I), (II) and (III), respectively. The influence of common and possible interfering species, pharmaceutical additives and some related pharmacological action drugs was investigated using separate solution method and no interference was found. The stability indicating using forced degradation of acebutolol hydrochloride was studied. The standard addition method was used for determination of the investigated drug in its pharmaceutical dosage forms and biological fluids. The results were validated and statistically analysed and compared with those from previously reported methods.     

Potentiometric Study of Coated Graphite Electrode and Polymeric Membrane Electrode for the Determination of Sm3+ Ion

Preliminary studies on the two Schiff bases N2‐((3H‐indol‐3‐yl)methylene)‐6‐phenyl‐1,3,5‐triazine‐2,4‐diamine (L₁) and N2,N4‐bis((3H‐indol‐3‐yl)methylene)‐6‐phenyl‐1,3,5‐triazine‐2,4‐diamine (L₂) have shown that they can act as Sm³⁺ selective electrodes. The performances of a polymeric membrane electrode and a coated graphite electrode based on L₂ were compared and the CGE proved to be better, as it shows a low detection limit of 1.8×10^?8 mol L^?1, a Nernstian slope of 19.6±0.4 mV decade^?1 of activity with a response time of 11 s in the pH range of 3.0–9.0. The CGE was used to determine Sm³⁺ in medicinal plants and soil samples. It was also used to determine fluoride ions in mouthwash samples and in toothpaste.     

New Ion‐Pair Based All‐Solid‐State Surfactant Sensitive Sensor for Potentiometric Determination of Cationic Surfactants

Cationic surfactants of different types were determined using a few potentiometric sensors based on ion‐pair complexes (dodecyldimethylbenzylammonium dodecylsulfate, dodecylmethylbenzylammonium dodecylbenzensulfonate, tetrahexadecylammonium dodecylsulfate and Hyamine (benzethonium dodecylsulfate)) as sensing materials. The response of the all‐solid state surfactant sensitive electrode based on a Teflonized graphite conducting substrate, coated with a PVC membrane containing sensing material, was investigated in the solutions of Hyamine and hexadecyltrimethylammonium ion in the concentration range from 1 μM to 10 mM. Potentiometric surfactant cation titration has been performed using sodium dodecylsulfate as titrant and an ion‐pair‐based surfactant sensitive electrode as a potentiometric indicator. Several commercial surfactant products have also been titrated and the results were compared with those obtained with two‐phase standard titration method.     

Potentiometric determination of antihistaminic diphenhydramine hydrochloride in pharmaceutical preparations and biological fluids using screen-printed electrode

The performance characteristic of sensitive screen-printed (SPE) and carbon paste (CPE) electrodes was investigated for the determination of diphenhydramine hydrochloride (DPH) drug in pure, pharmaceutical preparations and biological fluids. Different experimental conditions namely types of materials used to prepare the working electrode (plasticizer), titrant, pH, temperature and life time were studied. Under these conditions, the SPE shows the best performance than CPE with respect to total potential change and potential break at the end point. The SPE and CPE exhibit suitable response to DPH in a concentration range of 1.0.10^{− 2} to 1.0.10^{− 6} mol/L with a limit of detection 9.70.10^{− 7} and 9.80.10^{− 7} mol/L, respectively. The slope of the system was 55.2 ± 1.0 and 54.7 ± 1.0 mV/decade over pH range 3.0–8.0 and 3–7 for SPE and CPE, respectively. Selectivity coefficients for DPH relative to a numbers of potential interfering substances were investigated. The SPE and CPE show a fast response time of 10 and 16 s and were used over a period of 2 months with a good reproducibility. The sensors were applied successfully to determine DPH in pharmaceutical preparations and biological fluids. The results are compared with the official method.     

Selective Determination of Zn2+ Ion in Various Environmental,Biological and Medicinal Plant Samples Using a Novel Coated Graphite Electrode

Novel Zn²⁺ ion‐selective PVC based coated graphite electrodes were fabricated using the ionophores N‐((1H‐indol‐3‐yl)methylene)thiazol‐2‐amine (I₁), N‐((1H‐indol‐3‐yl)methyl)‐thiazol‐2‐amine (I₂) and 1‐((1H‐indol‐3‐yl)methylene)urea (I₃). Their potentiometric performance was examined in dependence of the addition of plasticizers and anion excluders and compared. It is found that the coated graphite electrode with the composition I₁:KTpClPB:o‐NPOE:PVC=9 : 1.5 : 51 : 38.5 is the best with respect to the wide working concentration range (4.2×10^?8–1.0×10^?1 mol L^?1), low detection limit (1.6×10^?8 mol L^?1) and wide pH range of 3.0–8.0. The proposed electrode was successfully applied to quantify Zn²⁺ in various environmental, biological and medicinal plant samples and used as indicator electrode.     

Determination of Cinnarizine in Pure and Pharmaceutical Formulations

Two simple, rapid and sensitive extractive spectrophotometric methods have been developed for the assay of cinnarizine (CNR) in pure and pharmaceutical formulations. The methods are based on the formation of chloroform soluble ion‐association complexes of CNR with thymol blue (TB) and with cresol red (CR) inNaOAc‐AcOH buffer of pH 3.6 for TB and in KCl‐HCl buffer of pH 1.6 for CR with absorption maxima at 405 nm and at 403 nm for TB and CR, respectively. Reaction conditions were optimized to obtain the maximum color intensity. The systems obeyed Beer's law in the range of 0.6–15.8 and 0.8–16.6 μg mL^?1 for TB and CR, respectively. Various analytical parameters have been evaluated and the results have been validated by statistical data.     

Electrochemical Oxidation of Pentoxifylline and its Analysis in Pure and Pharmaceutical Formulations at a Glassy Carbon Electrode

Abstract

The oxidative behavior of pentoxifylline was studied at a glassy carbon electrode in phosphate buffer solutions using cyclic and differential-pulse voltammetry. The oxidation process was shown to be irreversible over the pH range (3.0–9.0) and was diffusion controlled. The possible mechanism of the oxidation of pentoxifylline was investigated by means of cyclic voltammetry and UV-Vis spectroscopy. An analytical method was developed for the determination of pentoxifylline in phosphate buffer solution at pH 3.0 as a supporting electrolyte. The anodic peak current varied linearly with pentoxifylline concentration in the range 2.0 × 10^?8 M to 6.0 × 10^?7 M of pentoxifylline with a limit of detection (LOD) of 4.42 × 10^?10 M. The proposed method was applied to the determination of pentoxifylline in pure and pharmaceutical formulations.     

A Biomimetic Potentiometric Sensor Using Molecularly Imprinted Polymer for the Cetirizine Assay in Tablets and Biological Fluids

Despite the increasing number of applications of molecularly imprinted polymers (MIPs) in analytical chemistry, the construction of a biomimetic potentiometric sensor remains still challenging. In this work, a biomimetic potentiometric sensor, based on a non‐covalent imprinted polymer was fabricated for the recognition and determination of cetirizine. The MIP was synthesized by precipitation polymerization, using cetirizine dihydrochloride as a template molecule, methacrylic acid (MAA) as a functional monomer and ethylene glycol dimethacrylate (EGDMA) as a cross linking agent. The sensor showed high selectivity and a sensitive response to the template in aqueous system. The MIP‐modified electrode exhibited Nernstian response (28.0±0.9 mV/decade) in a wide concentration range of 1.0×10^?6 to 1.0×10^?2 M with a lower detection limit of 7.0×10^?7 M. The electrode has response time of ca. 20 s, high performance, high sensitivity, and good long term stability (more than 5 months). The method was satisfactory and used to the cetirizine assay in tablets and biological fluids.     

Design of an Imipramine‐Selective Electrode Based on an Ion‐Pair and its Application to Pharmaceutical Analysis

Ion‐selective electrodes play an important role in pharmaceutical analysis due to their simplicity, rapidity and accuracy over some other analytical methods. This research introduces the design of an ion‐pair of imipramine‐tetraphenyl borate (IMP‐TPB) based PVC membrane sensor for IMP hydrochloride determination. Effect of the membrane composition, the pH influence and the effect of lipophilic anionic additives on the response characteristics of the electrode were investigated. After a series of experiments, the best electrode performance was accomplished with a membrane composition of 30% PVC, 63% DBP, 5% (IMP‐TPB) and 2% (NaTPB). This electrode illustrated a fast (15 s), stable and Nernstian response across a relatively wide IMP hydrochloride concentration range (10^?5 to 10^?5 M), in the pH range of (3.0–8.0), and it can be used for at least two months without any measurable change in sensitivity. Additionally, the interference between IMP and several drugs and common inorganic anions was negligible as shown by the potentiometric selectivity coefficient data. The membrane sensor was successfully applied to the determination of IMP in tablets and human urine samples, and very good recovery results were obtained.     

Polybenzoin Based Sensor for Determination of 2thiouracil in Biological Fluids and Pharmaceutical Formulations

A carbon paste electrode was modified by electropolymerisation of benzoin using voltammetric technique. A novel polybenzoin modified carbon paste electrode (PB‐CPE) was developed for use as a detector in cyclic voltammetry and differential pulse adsorptive stripping voltammetry for the sensitive determination of 2thiouracil (2TU). The atomic force microscopy was applied to characterize the surface morphology of PB‐CPE. The modified electrode showed excellent electrocatalytic activity for the oxidation of 2TU. The oxidation process was irreversible over the pH range studied and exhibited a diffusion controlled behavior. All experimental parameters have been optimized. The peak current for the stripping of 2TU was found to be linear over the concentration range of 0.2–1.2 µM, with a detection limit of 2.21 nM. The practical application of the PB‐CPE in the determination of 2TU in human biological fluids and pharmaceutical samples were demonstrated that it has high sensitivity and good selectivity.     

Heterogeneous Membrane and Coated Wire Type Electrode with Chitosan as Ionophore in the Potentiometric Determination of Glutamate: Comparative Study

This study reports on two types of glutamate sensors based on chitosan, i) heterogeneous membrane and ii) coated wire (CWE). The linearity ranges are: i) membrane, 1.0×10^?5 to 1.0×10^?1 M and ii) CWE, 1.0×10^?5 to 1.0×10^?3 M. The LODs, and pH ranges are i) membrane, 5.0×10^?6 M and 4–8 and ii) CWE, 1.0×10^?5 M and 3–5, respectively. The presence of ionic species normally found in foodstuffs did not interfere in both electrodes. Interference in CWE was minimized by prior dilution of the sample. The CWE was further investigated for on‐line analysis. The material for proposed electrodes was cheaper and environmental friendly. Hence, they were suggested as alternative tools for the analysis of glutamate.     

Determination of Trace Amounts of Lorazepam by Adsorptive Cathodic Differential Pulse Stripping Method in Pharmaceutical Formulations and Biological Fluids

Abstract

A new adsorptive cathodic differential pulse stripping voltammetry method for the direct determination of lorazepam at trace levels in pharmaceutical formulations and biological fluids is proposed. The procedure involves an adsorptive accumulation of lorazepam on a hanging mercury drop electrode (HMDE), followed by reduction of adsorbed lorazepam by voltammetric scan using differential pulse modulation. The optimum conditions for the analysis of lorazepam are pH=2 using Britton‐Robinson (B‐R) buffer, accumulation potential of ?0.2 V (vs. Ag/AgCl), and accumulation time of 40 sec. The peak current is proportional to the concentration of lorazepam, and a linear calibration graph is obtained at 0.05–1.15 µg mL^?1. A relative standard deviation of 2.41% (n=3) was obtained, and the limit of detection was 0.019 µg mL^?1. The capability of the method for the analysis of real samples was evaluated by determination of lorazepam in pharmaceutical preparations and biological (urine and plasma) fluids with satisfactory results.     

Kinetic and Spectrophotometric Determination of Thioctic Acid in Bulk and Pharmaceutical Formulations

Three simple and sensitive spectrophotometric methods were developed for the determination of thioctic acid in bulk and in its pharmaceutical preparations using iron(III) as an oxidizing agent. Method A is based on kinetic investigation of oxidation reaction of the drug with iron(III) and a subsequent chelation of the produced iron(II) with ferricyanide to form prussian blue colored product at room temperature for a fixed time of 15 minutes at 750 nm. Methods B and C are based on oxidation of the studied drug with iron(III). The equivalent iron(II) produced is allowed to react with either o‐phenanthroline or bipyridyl to give colored species measurable at 510, 522 nm, respectively. Regression analysis of Beer‐Lambert plots showed a good correlation in the concentration ranges of 0.4–4 μg/mL with a detection limit of 0.095 μg/mL for method A and 0.5–5 μg/mL with detection limits 0.137 and 0.127 for method B and C, respectively. The three methods were successfully applied for the determination of the drug in its dosage forms. The percentage recoveries were 99.88 ± 1.40, 99.98 ± 1.26 and 100.64 ± 1.07, respectively.     

Potentiometric Quantification of the Benzoate Ion in Nonalcoholic Beverages Using a Solid Electrode Modified with a Polypyrrole‐Based Selective Membrane

This work presents the results obtained on the construction of a potentiometric ion‐selective electrode based on a polypyrrole (PPy) selective membrane to quantify the benzoate ion in nonalcoholic beverages. The electrode modification with benzoate (Benz^?1) ion doped‐Ppy was carried out under an imposed potential, while the electrosynthesis optimization was undertaken using the modified Simplex method, such that the film’s sensitivity was maximized toward the benzoate ion. The maximum sensitivity recorded was ?52.02±1.55 mV/decade [Benz^?1] using a graphite powder‐araldite resin composite electrode. During the modified electrode’s characterization it was found out that the response and drift were relatively short, namely 2 min and 0.4 mV min^?1 respectively, within the 7 to 9 pH range, exhibiting a detection limit of 7×10^?4 mol L^?1 and a quantification range of 3×10^?3 at 10^?1 mol L^?1. Selectivity coefficients were evaluated with the Matched Potential Method obtaining in all cases values much less than 1. The benzoate concentration in commercially available juices and sweetened beverages was evaluated comparing the results obtained with the proposed ion‐selective electrode and those of HPLC, the usually accepted technique. A statistical analysis of the results led to the conclusion that there exists no meaningful difference between the results obtained with both techniques, which shows the usefulness of the ion‐selective electrode to proceed with the quantification in real samples.