A Novel Potentiometric Detection Strategy for the Determination of Amlodipine Besylate Based on Functionalized Particles

A novel potentiometric strategy based on functionalized magnetite nanoparticles and microparticles were compared with the classical potentiometric strategy. This strategy provided nano‐ and microsized particles that were highly dispersed and coated with ionophore and plasticizer to promote an in situ cooperative ion‐pairing interaction between the ionophore and the analyte present in inner solution of sensor membrane, compared to the classical technique. Three amlodipine (AML) sensors were constructed using functionalized nanoparticles in sensor 1; microparticles in sensor 2, as ionophores, and the polymeric membrane ionophoric property in sensor 3.     

Platinum porphyrins as ionophores in polymeric membrane electrodes

A comparative study of Pt(II)- and Pt(IV)-porphyrins as novel ionophores for anion-selective polymeric membrane electrodes is performed. Polymeric membranes of different compositions, prepared by varying plasticizers, cationic and anionic additives and Pt porphyrins, have been examined by potentiometric and optical techniques. Pt porphyrin-based devices were found to exhibit enhanced potentiometric selectivity toward iodide ion compared to electrodes based on a typical anion-exchanger (e.g. tridodecylmethylammonium chloride). It is shown that Pt(II)-porphyrins function as neutral anion carriers within the electrode membranes, while those based on Pt(IV)TPPCl(2) operate via a mixed mode carrier mechanism, evidencing also a partial reduction of the starting ionophore to Pt(II)TPP. Spectrophotometric measurements of thin polymeric films indicate that no spontaneous formation of hydroxide ion bridged porphyrin dimers occurs in the membrane plasticized both with high or low dielectric constant plasticizer, due to a low oxophilicity of central Pt. The computational study of various anion-Pt(IV)TPPCl(2) complex formation by means of semi-empirical and density functional theory (DFT) methods revealed a good correlation between calculated and measured ionophore selectivity.     

Selective potentiometric determination of zolpidem hemitartrate in tablets and biological fluids by using polymeric membrane electrodes

The construction and electrochemical response characteristics of 4 polymeric membrane sensors were investigated for potentiometric determination of zolpidem hemitartrate. The construction of the 4 sensors was based on the formation of ion-pair complexes between the drug cation and ionic sites in the ratio of 1:2, respectively. Two of the sensors were constructed by using ammonium reineckate or ammonium tungstate as the fixed ionic site in a polymeric matrix of polyvinyl chloride (PVC) (sensors 1 and 2). Linear responses over the concentration range of 10(-5)-10(-3)M, with cationic slopes of 30 and 30.7 mV per concentration decade, were obtained by using sensors 1 and 2, respectively. The third sensor was fabricated by using PVC carboxylate (PVC-COOH). The dissociated COOH groups in the PVC-COOH act as a mediator and/or ionic site. A linear response was obtained over the concentration range of 10(-5)-10(-2)M with a cationic slope of 29 mV per concentration decade. Sensor 4 was fabricated by using 2,6-didodecyl-beta-cyclodextrin as the ionophore, polyurethane (Tecoflex) as a polymeric matrix, and potassium tetraphenyl borate as the ionic site; it showed a linear response over the concentration range of 10(-7)-10(-2)M with a cationic slope of 28.9 mV per concentration decade. The direct potentiometric determination of zolpidem hemitartrate in pure forms by using the 4 proposed sensors gave average recoveries of 98.5+/-0.7, 99.4 +/-0.2, 100.7+/-0.10, and 99.8+/-0.1% for sensors 1-4, respectively. The results obtained by the proposed procedures were statistically analyzed and compared with those obtained by using a reported method. The 4 proposed sensors were also applied successfully to the determination of the drug in tablets and in biological fluids. Average recoveries obtained by using sensors 1, 2, 3, and 4 for drug assay of tablets were 99.6+/-0.6, 100+/-0.7, 99.7+/-0.4, and 99.5+/-0.8%, respectively. The presence of tablet excipients did not interfere with the determination of the drug or with the accuracy and precision of the 4 proposed methods. The methods were also used to determine the drug in the presence of its degradates and thus could be used as stability-indicating methods.     

Nitrite‐Selective Electrode Based On Cobalt(II) tert‐Butyl‐Salophen Ionophore

A series of polymeric nitrite‐selective electrodes containing a new lipophilic ionophore Co(II) tert‐butyl‐salophen is reported. The stability of Co(II) ionophores within a PVC‐based membrane was investigated by leaching experiments. Different membrane compositions were explored in order to reach the lowest possible limit of detection for a PVC‐based nitrite selective polymeric membrane electrode containing this ionophore. The optimal electrode showed a limit of detection of 2×10^?6 M and exhibited four orders of magnitude of discrimination over nitrate, chloride and bromide. The electrodes were evaluated in undiluted human urine and attest to the robustness of the ionophore.     

Highly sensitive and selective solid-contact calcium sensor based on Schiff base of benzil with 3-aminosalycilic acid covalently attached to polyacrylic acid amide for health care

Solid-state potentiometric calcium sensors based on newly synthesized Schiff’s base of 3-aminosalycilic acid with benzil [2-hydroxy-3-(2-oxo-1,2-diphenylethylidene)amino) benzoic acid] ionophore I and with isatin [2-hydroxy-3-(2-oxoindolin-3-ylidene amino)benzoic acid] ionophore II ionophores and their covalently attached to polyacrylamide ionophores III and IV, respectively, were developed. The all-solid-state sensors were constructed by the application of a thin film of polymeric membrane cocktail onto gold electrodes that were pre-coated with the conducting polymer poly (3,4-ethylenedioxy-thiophen) as an ion and electron transducer. More than 40 sensors with membranes containing plasticized PVC or poly(butyl methacrylate-co-dodecyl methacrylate as a plasticizer-free membrane matrix were investigated. The constructed sensors contained various amounts of the different ionophores with and without anionic lipophilic additive. The sensor containing 10% of ionophore III and 3% tetra (p-chlorophenyl) borate in acrylate copolymer exhibited a stable potentiometric response over a wide pH range of 4–9. It possessed a linear concentration range of 6 10^?10 to 1 10^?2 mol L^?1 with a Nernstian slope of 28.5 mV/decade and a limit of detection (LOD) of 2 10^?10 mol L^?1. It exhibited a good selectivity for calcium to other cations. The selectivity coefficients towards different mono-, di- and trivalent cations were determined with the fixed interference method (FIM) and separate solution method (SSM). The sensor’s life time is more than 3 months, without significant deterioration in the slope. The proposed sensors were utilized for the determination of calcium concentration in serum. The results were compared with those obtained from routine clinical laboratory electrolyte analyser. The results reveal that the all-solid-state calcium sensor is promising for the point of care testing.     

Polymethacrylate polymers with appended aluminum(III)-tetraphenylporphyrins: Synthesis, characterization and evaluation as macromolecular ionophores for electrochemical and optical fluoride sensors

The synthesis and characterization of a novel polymethacylate polymer with covalently linked Al(III)-tetraphenylporphyrin (Al(III)-TPP) groups is reported. The new polymer is examined as a potential macromolecular ionophore for the preparation of polymeric membrane-based potentiometric and optical fluoride selective sensors. To prepare the polymer, an Al(III) porphyrin monomer modified with a methacrylate functionality is synthesized, allowing insertion into a polymethacrylate block copolymer (methyl methacrylate and decyl methacrylate) backbone. The resulting polymer can then be incorporated, along with appropriate additives, into conventional plasticized poly(vinyl chloride) films for testing electrochemical and optical fluoride response properties. The covalent attachment of the Al(III)-TPP ionophore to the copolymer matrix provides potentiometric sensors that exhibit significant selectivity for fluoride ion with extended lifetimes (compared to ion-selective membrane electrodes formulated with conventional free Al(III)-TPP structure). However, quite surprisingly, the attachment of the ionophore to the polymer does not eliminate the interaction of Al(III)-TPP structures to form dimeric species within the membrane phase in the presence of fluoride ion. Such interactions are confirmed by UV/visible spectroscopy of the blended polymeric films. Use of the new polymer-Al(III)-TPP conjugates to prepare optical fluoride sensors by co-incorporating a lipophilic pH indicator (4′,5′-dibromofluorescein octadecyl ester; ETH7075) is also examined and the resulting optical sensing films are shown to exhibit excellent selectivity for fluoride, with the potential for prolonged operational lifetime.     

Microsized graphite sensors for potentiometric determination of cyclobenzaprine hydrochloride in pure powder, tablets, and plasma

Two cyclobenzaprine hydrochloride (CZ) microsized graphite selective sensors were investigated with dibutylsebacate as a plasticizer in a polymeric matrix of carboxylated polyvinyl chloride (PVC-COOH) in the case of sensor 1, based on the interaction between the drug and the dissociated COOH groups in the PVC-COOH. Sensor 2 was based on the interaction between the drug and ammonium reineckate, which acted as anionic electroactive material in the presence of polyvinyl chloride matrix. The two sensors were constructed by using 2-hydroxy propyl beta-cyclodextrin as an ionophore, which has a significant influence on increasing the membrane sensitivity and selectivity of both sensors. Fast and stable Nernstian responses of 1 x 10(-5) - 1 x 10(-2) and 1 x 10(-4) - 1 x 10(-2) M for the two sensors, respectively, with slopes of 58.6 and 55.5 mV/decade, respectively, over the pH range 2-4 were obtained. The proposed method displayed useful analytical characteristics for determination of CZ in its pure powder form with average recoveries 99.95 +/- 0.23 and 99.61 +/- 0.34% for sensors 1 and 2, respectively, and in plasma with good recoveries. The sensors were also used to determine the intact drug in the presence of its degradate and, thus, could be used as stability-indicating methods. The obtained results by the proposed methods were statistically analyzed and compared with those obtained by the U.S. Pharmacopeia method; no significant difference for either accuracy or precision was observed. Results obtained with the two electrodes revealed their performance characteristics, which were evaluated according to International Union of Pure and Applied Chemistry recommendations.     

Graphene-based Disposable Electrochemical Sensor for Chlorhexidine Determination

In this work, simple, reliable, eco-friendly, and quantitative electrochemical sensors were developed to detect chlorhexidine Digluconate (CHX) in a variety of dosage forms, including mouthwashes and intimate douches, as well as chlorhexidine in spiked human saliva. Without any sample pre-treatment or extraction processes, CHX was measured in colored aqueous formulations. Based on carbon screen-printed electrodes, two potentiometric sensors (sensors I and II), utilizing graphene nanocomposites (Gr-NC), were designed (SPEs). An ionophore, 2-hydroxypropyl-β-cyclodextrin, was doped into the Poly Vinyl Chloride (PVC) polymeric membrane to improve sensor selectivity.     

Quantitive binding constants of H(+)-selective chromoionophores and anion ionophores in solvent polymeric sensing membranes

The binding properties of neutral or charged chromoionophores and anion ionophores in solvent polymeric membranes were characterized in situ by the so-called sandwich membrane method. Acidity constants (pK(a)) of eight chromoionophores (ETH 5294, ETH 2439, ETH 5350, ETH 5418, ETH 5315, ETH 7061, ETH 7075, ETH 2412) were measured in bis(2-ethylhexyl)sebacate (DOS) and o-nitrophenyloctylether (NPOE) plasticized poly(vinyl chloride) (PVC) membranes commonly used in optical and potentiometric ion sensors. The pK(a) values of all chromoionophores in DOS membranes are by 2-3 orders of magnitude smaller than in NPOE membranes. The weak alkali metal ion binding properties with neutral H(+)-chromoionophore and anion binding with electrically charged chromoionophores were also studied quantitatively. The complex formation constants of the commercially available Co(III)cobyrinate nitrite ionophore and the organomercury chloride ionophore, ETH 9009, were also measured. The very low stability constant observed for ETH 9009 (logbeta(2)=3.60+/-0.03 in PVC-DOS and 3.61+/-0.01 in PVC-NPOE) was explained by the decomposition of the ionophore in contact with chloride samples. On the other hand, the electrically charged nitrite ionophore showed strong complexation with nitrite ions, with logbeta=10.58 and 10.59 in DOS and NPOE membranes, respectively. In contrast to cation ionophores, the stability constant of the NO(2)(-) ionophore does not change with different plasticizers.     

Cross-sensitive chemical sensors based on tetraphenylporphyrin and phthalocyanine

The properties of solvent polymeric membrane sensors based on 5,10,15,20-tetraphenylporphyrin (TPP) and phthalocyanine (PHC) have been investigated. The sensitivity and selectivity of sensors towards wide range of mono- and di-valent cations have been measured. The selectivity towards the transition metal ions for TPP-based sensor does not correspond to the cation lipophilicity sequence. The dependence of response on pH was studied. The cross-sensitivity parameters, including average response slope, signal-to-noise ratio and “non-selectivity” factor for all sensors were calculated and compared. The influence of plasticizer and ionic additive on the response of sensors was characterized using principal component analysis (PCA).     

Comparative study of 2-hydroxy propyl beta cyclodextrin and calixarene as ionophores in potentiometric ion-selective electrodes for neostigmine bromide

Three novel neostigmine bromide (NEO) selective electrodes were investigated with 2-nitrophenyl octyl ether as a plasticiser in a polymeric matrix of polyvinyl chloride (PVC). Sensor 1 was fabricated using tetrakis(4-chlorophenyl)borate (TpClPB) as an anionic exchanger without incorporation of an ionophore. Sensor 2 used 2-hydroxy propyl β-cyclodextrin as an ionophore while sensor 3 was constructed using 4-sulfocalix-8-arene as an ionophore. Linear responses of NEO within the concentration ranges of 10⁻⁵ to 10⁻², 10⁻⁶ to 10⁻² and 10⁻⁷ to 10⁻² mol L⁻¹ were obtained using sensors 1, 2 and 3, respectively. Nernstian slopes of 51.6 ± 0.8, 52.9 ± 0.6 and 58.6 ± 0.4 mV/decade over the pH range of 4-9 were observed. The selectivity coefficients of the developed sensors indicated excellent selectivity for NEO. The utility of 2-hydroxy propyl β-cyclodextrin and 4-sulfocalix[8]arene as ionophores had a significant influence on increasing the membrane sensitivity and selectivity of sensors 2 and 3 compared to sensor 1. The proposed sensors displayed useful analytical characteristics for the determination of NEO in bulk powder, different pharmaceutical formulations, and biological fluids (plasma and cerebrospinal fluid (CSF)) and in the presence of its degradation product (3-hydroxyphenyltrimethyl ammonium bromide) and thus could be used for stability-indicating methods.     

Optical acetylcholine sensor based on free base porphyrin as a chromoionophore

In this work, the possibility of application of free base porphyrin as a lipophilic pH chromoionophore for the preparation of optical cation-selective sensors was investigated. The properties of polymeric membranes, containing porphyrins of different structures, namely tetraphenylporphyrin (TPP) and octaethylporphyrin (OEP), were compared. Changes in equilibrium between protonated and deprotonated form of porphyrin, resulting from variations in ACh concentration, were evaluated. The influence of various factors (kind and quantity of anionic additive and porphyrin in the membrane phase, pH of sample solution) on initial equilibrium was studied. The best membrane composition was chosen as: TPP 3 wt.%, KTFPB 175 mol.% relative to ionophore, PVC:o-NPOE (1 : 4) and measuring buffer solution: 0.05 M MES, pH 4.5. Selectivity, response stability, reversibility and repeatability tests were carried out for chosen sensor. Developed sensor allowed for the determination of a model analyte, acetylcholine, at the concentration range of 10(-5) to 10(-2) M, both in stationary and flow-injection system. Sensor response was reversible and repeatable in the mentioned concentration range.     

Membrane-Based Continuous Remover of Trifluoroacetic Acid in Mobile Phase for LC-ESI-MS Analysis of Small Molecules and Proteins

We developed a "continuous" trifluoroacetic acid (TFA) remover based on electrodialysis with bipolar membrane for online coupling of liquid chromatography (LC) and electrospray ionization mass spectrometry (ESI-MS) using TFA containing mobile phase. With the TFA remover as an interface, the TFA anion in the mobile phase was removed based on electrodialysis mechanism, and meanwhile, the anion exchange membrane was self-regenerated by the hydroxide ions produced by the bipolar membrane. So the remover could continuously work without any additional regeneration process. The established LC-TFA remover-MS system has been successfully applied for the qualitative and quantitative analysis of small molecules as well as proteins.     

Microfabricated Solid-contact Potentiometric Sensor for Determination of Tedizolid Phosphate,Application to Content Uniformity Testing

Solid contact sensors were designed for determination of the antibiotic prodrug tedizolid phosphate. The sensors are based on; microfabricated copper as cost-effective electrode substrate and graphene layer as a transducer. The ion sensing PVC polymeric membrane was optimized by proper selection of the anion exchanger. The graphene layer was characterized by scanning electron microscopy, Raman spectroscopy, FT-IR, besides measuring electrochemical impedance for the fabricated sensors. The potential drift decreased down to 0.133 mV h⁻¹ compared to 6.67 mV h⁻¹ for graphene free sensor. The sensors have been used to determine tedizolid phosphate in its pharmaceutical formulation and content uniformity testing applications.     

Acid mediated hydrolysis of blueberry anthocyanins

Acid mediated hydrolysis of anthocyanins was studied using capillary zone electrophoresis (CZE). A commercially available wild blueberry (Bilberry) extract was dissolved in different concentrations of TFA (0.1, 1, 3, 9%), then was subjected to thermodecomposition reaction at 95 degrees C. After the reaction, the samples were analyzed by CZE. The hydrolysis rate of each anthocyanin and the formation of the aglycon were determined by the change in the peak pattern of the anthocyanins in the electropherogram. Each anthocyanin peak decreased time dependently in a first order kinetic fashion. It was revealed that the hydrolysis rate of each anthocyanin was determined primarily by the type of conjugated sugar and not by the aglycon structure. The rate constant of anthocyanin hydrolysis was in the following order, arabinoside>galactoside>glucoside without regard to the aglycon structure. The kinetic behavior of this anthocyanin hydrolysis together with the CZE mobility allowed us to identify an unknown CZE peak as delphinidin 3-O-beta-arabinoside. At low TFA concentration, significant decomposition of the anthocyanidin nucleus occurred, but the glycoside hydrolysis predominated at high TFA concentration. It was further revealed that the aglycon released reacted successively to form polymeric products at higher TFA conditions.     

Response Characteristics of Copper‐Selective Polymer Membrane Electrodes Based on a Newly Synthesized Macrocyclic Calix[4]arene Derivative as a Neutral Carrier Ionophore

A novel macrocyclic calix[4]arene derivative was examined as an ionophore for ion‐selective polymeric membrane electrode toward Cu⁺² ions. The sensor showed a near Nernstian response for Cu(II) ions over a concentration range from 8.1×10^?6 to 1.0×10^?2 mol L^?1 with a slope of 34.2±0.4 mV per concentration decade in an acidic solution (pH 5). The limit of detection was 0.47 µg mL^?1. It had a response time of <20 s and can be used for at least 3 months without any divergence in potentials. The influence of plasticizer as well as the amount of lipophilic anionic site additive in the sensing membrane was discussed. It was shown that membrane electrodes formulated with the ionophore and appropriate anionic additive exhibited enhanced potentiometric response toward Cu²⁺ over all other cations tested. Since selectivity toward Cu²⁺ ions is decreased in the presence of high amount of the anionic additive, the ionophore can function as neutral carriers within the organic membrane phase. Validation of the assay method revealed good performance characteristics, including long life span, good selectivity for Cu²⁺ ions over a wide variety of other metal ions, long term response stability, and high reproducibility. The sensors were used for direct measurement of copper content in different rocks collected from different geological zones. The results agreed fairly well with data obtained using atomic absorption spectrometry.     

双层夹心膜电极电位法测定溶剂聚合物膜中杯芳烃-金属离子配合物的生成常数

以双层夹心膜电极为指示电极,采用电位法测定了聚合物膜中活性离子载体杯[6]芳烃乙酯与金属离子形成的配合物的生成常数.提出了一种新的测定夹心膜膜电位的方法,由测得的膜电位可计算出配合物的生成常数.以杯[6]芳烃乙酯为离子载体,测得其与Li⁺,Na⁺,K⁺,Cs⁺和NH⁺₄等离子的配合物生成常数的对数值分别为6.14,6.48.6.74,7.43和6.21.制备了以Cs⁺为主离子的选择性电极,采用固定干扰法,测得对Li⁺,Na⁺,K⁺和NH⁺₄等离子的选择性系数的对数值分别为-3.33,-2.54,-1.6和-2.9.实验结果表明,配合物的生成常数与选择性系数之间有较好的相关性.生成常数越大,电极对相应离子的选择性越高.     

Synthesis and Structural Characterization of One-dimensional Polynuclear Complex [La(bipyN2O2)(TFA)3]n

Some of rare earth-β-diketone-2,2'-bipyridyl-N,N'-dioxide ternary complexes have been studied1,2. Very few work dealing with 4,4'-bipyridyl-N,N'-dioxide complex appeared. In our previous work, some ternary complexes of europium with β-diketones and 4,4'-bipyridyl-N,N'-dioxide with the formula of Ln (β-dik)3·0.5(bipyN2O2) have been isolated and well characterized.3 Here we report a newly synthesized ternary complex [La (bipyN2O2) (TFA)3]n. Crystal analysis showed it had an infinite on…     

Nitrogenous synergists induced potentiometric response to metal ions with polymeric liquid membranes containing thenoyltrifluoroacetone as an ionophore.

The effects of nitrogenous synergists on the potentiometric responses to divalent transition metal ions were investigated concerning polymeric liquid membranes containing thenoyltrifluoroacetone (Htta) as an ionophore. The tested synergists were pyridine (py) and 4,4'-dioctyl-2,2'-bipyridyl (C8bpy). The potentiometric responses to metal ions, such as Cd2+, Co2+, Ni2+ and Zn2+, were induced by adding the synergists into the liquid membrane systems. The coexistence of Htta and a synergist was necessary for generating the membrane potential. The tta- anion adsorbed at the liquid membrane/solution interface and the complex formation between the synergist and a given metal ion appeared to participate in preferential uptake of metal ions.     

Visible and FTIR Microscopic Observation of Bisthiourea Ionophore Aggregates in Ion‐Selective Electrode Membranes

Since conventional response models for ionophore‐based ISEs are based on the assumption of a homogeneous membrane phase, they cannot accurately predict the response of membranes containing self‐aggregating ionophores. However, meaningful conclusions about the relationship between ionophore structure and potentiometric responses can only be drawn if ionophore aggregation is properly recognized. This study demonstrates that dark field visible microscopy and FTIR microspectroscopy are valuable tools for the observation of such ionophore self‐aggregation and, thereby, the development of new ionophore‐based ISEs. Sulfate selective electrodes with solvent polymeric membranes containing bisthiourea ionophores that differ only by peripheral nonpolar substituents were shown to exhibit very different interferences from the sample pH. On one hand, optimized electrodes based on an ionophore with a phenyl substituent on each thiourea group ( 1 ) do not respond to pH at all and function well as sulfate‐selective electrodes. On the other hand, membranes containing a more lipophilic ionophore with two additional hexyl‐substituted adamantyl groups ( 2 ) exhibit severe pH interference at pH values as low as pH 5. The observation of membranes containing ionophore 2 with dark field visible microscopy and FTIR microspectroscopy shows supramolecular aggregation, and explains the startling difference between the potentiometric responses of the two types of electrodes.