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In the present study green chemistry was employed for synthesizing ZnO nanoparticles using the extract of black tea solid waste and Zn acetate dihydrate. The characterization of the green synthesized ZnO was conducted by XRD, SEM, HR-TEM, DLS and EDAX. Urine samples from donors under medication with Ibuprofen, Ephedrine and Propranolol were separated and collected through a diversion toilet. A batch experiment was conducted in order to determine the optimum dose of green synthesized ZnO nanoparticles for the removal of the pharmaceutical compounds from human urine. The determined optimum dose of the ZnO nanoparticles was 1.5 g/l. ZnO nanoparticle possess the ability to adsorb the Pharmaceutical active compounds (PACs) on the surface. In addition, it binds such adsorbed particles and facilitates their precipitation. Coagulant reagents react with some of the suspended and colloidal particles in water/wastewater to enhance their binding together, thus, allowing their removal in the subsequent treatment processes. The mechanism of aggregation consists of the combination of charge neutralization, entrapment, adsorption and/or complexion with the coagulant ions to form insoluble precipitate. Thus, the particles and colloids can be removed. A semi-pilot plant consisted of mixing tank for chemical coagulation using the predetermined ZnO nanoparticles followed by microfiltration unit, was designed and operated continuously for the treatment of the separated urine. The overall results of the semi-pilot study showed that the concentration of Ibuprofen, Ephedrine and Propranolol decreased from 5.0, 10.15 and 15.2 mg/l to 0.01, 0.10 and 0.03 mg/l respectively. The overall removal rate exceeded 99%. Meanwhile, the treatment system succeeded to improve the physical and chemical characteristics of the contaminated human urine. The treated urine could be safely used for agriculture purposes without any environmental threat. Keywords: ZnO nanoparticles, Green synthesis, Pharmaceutical removal, Chemical coagulation, Urine safe reuse, Membrane microfiltration

Novel potentiometric sensors for selective screening of sulfamethazine (SMZ) in pharmaceutical preparations and milk samples are reported. The sensor membranes were made from PVC matrix doped with magnesium(II)-, manganese(II)- and dichlorotin (IV)-phthalocyanines as ionophores and aliquat-336 and nitron/SMZ ion-pair complex as ion exchangers. These sensors revealed fast, stable and near-Nernstian anionic response for the singly charged sulfamethazine anion over the concentration range 10-2 - 10-5 M. The sensors exhibited good selectivity towards SMZ over most known anions, excipients and diluents commonly added in drug preparations. Validation of the proposed methods was demonstrated via evaluating the detection limit, linear response range, accuracy, precision (within-day repeatability) and between-day-variability. The sensors are easily interfaced with a double channel flow injection system and used for continuous monitoring of SMZ in drug formulations, spiked milk samples and biological tissues. The method offers the advantages of design simplicity, results accuracy, and automation feasibility.

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.

A novel poly(vinyl chloride) matrix membrane sensor responsive to 4-nitrophenylphosphate (4-NPP) substrate is described, characterized and used for the potentiometric assay of acid (ACP) and alkaline (ALP) phosphatase enzymes. The sensor is based on the use of the ion-association complex of 4-NPP anion with nickel(II)-bathophenanthroline cation as an electroactive material and nitrophenyloctyl ether (NPOE) as a solvent mediator. The sensor displays good selectivity and stability and demonstrates a near-Nernstian response for 4-NPP over the concentration range 9.6x10(-6) to 1.0x10(-2) M with an anionic slope of 28.6+/-0.3 mV decade(-1) and a detection limit of 6.3x10(-6) M over the pH range 4.5-10. The sensor is used to measure the decrease of a fixed concentration of 4-NPP substrate as a function of acid and alkaline phosphatase enzyme activities at optimized conditions of pH and temperature. A linear relationship between the initial rate of 4-NPP substrate hydrolysis and enzyme activity holds over 0.05-3.0 and 0.03-3.4 IU L(-1) of ACP and ALP enzymes, respectively. Validation of the method by measuring the lower detection limit, range, accuracy, precision, within-day repeatability and between-day-variability reveals good performance characteristics of the proposed sensor. The sensor is used for the determination of acid and alkaline phosphatase enzyme activities in biological fluids of some patients suffering from alcoholic cirrhosis, acute myelocytic leukemia, pre-eclampsia and prostatic cancer. The sensor is also utilized for assessment of alkaline phosphatase enzyme in milk and dairy products. The results obtained agree fairly well with data obtained by the standard spectrophotometric methods.

Trichosporon jirovecii yeast cells are used for the first time as a source of L-cysteine desulfhydrase enzyme (EC 4.4.1.1) and incorporated in a biosensor for determining L-cysteine. The cells are grown under cadmium stress conditions to increase the expression level of the enzyme. The intact cells are immobilized on the membrane of a solid-state Ag2S electrode to provide a simple L-cysteine responsive biosensor. Upon immersion of the sensor in L-cysteine containing solutions, L-cysteine undergoes enzymatic hydrolysis into pyruvate, ammonia and sulfide ion. The rate of sulfide ion formation is potentiometrically measured as a function of L-cysteine concentration. Under optimized conditions (phosphate buffer pH 7, temperature 37+/-1 degrees C and actual weight of immobilized yeast cells 100 mg), a linear relationship between L-cysteine concentration and the initial rate of sulfide liberation (dE/dt) is obtained. The sensor response covers the concentration range of 0.2-150 mg L(-1) (1.7-1250 micromol L(-1)) L-cysteine. Validation of the assay method according to the quality control/quality assurance standards (precision, accuracy, between-day variability, within-day reproducibility, range of measurements and lower limit of detection) reveals remarkable performance characteristics of the proposed biosensor. The sensor is satisfactorily utilized for determination of L-cysteine in some pharmaceutical formulations. The lower limit of detection is approximately 1 micromol L(-1) and the accuracy and precision of the method are 97.5% and +/-1.1%, respectively. Structurally similar sulfur containing compounds such as glutathione, cystine, methionine, and D-cysteine do no interfere.

A highly selective potentiometric sensor for thiocyanate ion based on the use of a newly synthesized organo-palladium ion exchanger complex dispersed in a plasticized poly(vinyl chloride) membrane is described. The sensor displays a Nernstian response (−57.8±0.2 mV decade−1) over a wide linear concentration range of thiocyanate (1.0×10−6–1.0×10−1 mol L−1 ), low detection limit (6.3×10−7 mol L−1), fast response (20 s), stable potential readings (±0.4 mV), good reproducibility (±0.9%), long term stability (8 weeks), high precision (±0.7%) and applicability over a wide pH range (4–10). Negligible interferences are caused by F−, Cl−, I−, Br−, NO3−, NO2−, CN−, SO42−, S2O32−, PO43−, citrate, acetate and oxalate ions. Under hydrodynamic mode of operation (FIA), the calibration slope is −51.1±0.1 mV decade−1, the linear response range is 1.0×10−5–1.0×10−1 mol L−1 SCN− and the sample throughput is 40–45 per hour. The sensor is satisfactory used for manual and flow injection potentiometric determination of SCN− in the saliva and urine of cigarette smokers and non smokers. The data agree fairly well with results obtained by the standard spectrophotometric technique. Direct potentiometry and potentiometric titration of SCN− with Ag+ are also monitored with the sensor.

Synthetic Sorel's cement [3Mg(OH)2 . MgCl2 . 8H2O], is used as a new adsorbent material for removal of chromium(VI) ion from wastewater effluents. Parameters including contact time, adsorbent dosage and pH are examined and optimized. The equilibrium data are fitted very well to the Langmuir and Freundlich isotherms rather than linear. The adsorption isotherm indicates that the monolayer coverage is 21.4 mg Cr(VI) ion per g of Sorel's cement. The adsorbent is considered as a better replacement technology for removal of Cr(VI) ion from aqueous solutions due to its low cost, good efficiency, fast kinetics, and simple preparation. It offers remarkable efficiency for Cr(VI) removal from wastewater compared with many other natural and synthetic adsorbents.

A novel spectrophotometric assay method for batch and flow injection determination of sulfite in beverages is described. The method involves a reaction with diaquacobyrinic acid heptamethyl ester (diaquacobester, DACbs) in acetate buffer of pH 3 to form a highly stable sulfite cobester complex (SO3Cbs). In the absence of sulfite, the reagent displays three absorption maxima at 349, 409 and 525 nm. Addition of sulfite is associated with the development of a new absorption band at 313 nm, an increase in the intensity of the band at 425 nm and a decrease in the absorbance of the bands at 349 and 525 nm. Variations of the absorptions at 313, 349, 425 and 525 nm are linearly proportional to sulfite concentrations over the range of 0.05-25 microg ml(-1)with a detection limit of 0.01-0.2 microg ml(-1). Negligible interferences are caused by most common ions. Validation of the method according to the quality assurance standards shows suitability for quality control assessment of sulfite in complex matrices without prior treatment. The method has the advantages of high selectivity, good sensitivity, fast reaction, high stability of the reagent and reaction product and absorbance measurements at four different wavelengths in the same run. The method is successfully applied to determine the sulfite contents of some beverages. The results compare fairly well with data obtained using the standard method.

Coated-wire (CW) and tubular (Tu) type membrane sensors for creatinine are developed. These consist of creatinine tungstophosphate(CTP), creatinine molybdophosphate (CMP) and creatinine picrolonate (CPC) ion-pair complexes as electroactive materials dispersed in plasticized poly(vinyl chloride) matrix membranes. Electrochemical evaluation of these sensors under static (batch) mode of operation reveals near-Nernstian response with slopes of 62.9, 58.1, and 55.2 mV decade−1 over the concentration range 1×10−2–5.0×10−6, 1×10−2–7.5×10−5, and 1×10−2−3.1×10−5 mol L−1. The lower detection limits are 0.39, 3.49, and 2.20 μg mL−1 creatinine with CTP, CMP and CPC membrane based sensors plasticized with o-NPOE, respectively. Tubular and coated wire CTP membrane sensors are incorporated in flow-through cells and used as detectors for flow injection analysis (FIA) of creatinine. The intrinsic characteristics of the detectors under hydrodynamic mode of operation in a low dispersion manifold are determined and compared with data obtained under static mode of operation. With 10−2 mol L−1 phosphate buffer of pH 4.5 as a carrier solution, the tubular and coated wire CTP detectors exhibit rapid response of 58.9 and 50.7 mV decade−1 over the concentration range 1×10−2–1×10−5 mol L−1 and detection limits of 0.39 μg mL−1 and 0.85 μg mL−1, respectively. Validation of the assay methods with the proposed sensors by measuring the lower detection limit, range, accuracy, precision, repeatability and between-day-variability reveals good performance characteristics confirming applicability for continuous determination of creatinine. The sensors are used for determining creatinine in human blood serum at an input rate of 40 samples per hour. No interferences are caused by creatine, most common anions, cations and organic species normally present in biological fluids. The results favorably compare with data obtained using the standard spectrophotometric method.

Two potentiometric sensors responsive to sildenafil citrate (SC) drug (the active component of viagra) are described, characterized, compared and used for drug assessment. The sensors are based on the use of the ion-association complexes of (SC) cation with tungstophosphate (TP) and reineckate (Re) anions as electroactive materials in plasticized poly(vinyl chloride) membranes. The sensors demonstrate fast near-Nernstian response for SC over the concentration ranges 1.0×10−2–7.9×10−7 and 1.0×10−2–1.0×10−6 M with detection limits of 0.53 and 0.67 μg ml−1 over pH 3–6 for TP and Re based membrane sensors, respectively. The sensors display good selectivity for SC drug over many nitrogeneous compounds, some inorganic cations and excipients and diluents commonly used in drug formulations. Validation of the assay methods with both sensors by measuring the lower detection limit, range, accuracy, precision, repeatability and between-day-variability reveals good performance characteristics confirming applicability for continuous determination of SC in pharmaceutical formulations and in spiked human serum. A membrane incorporating SC–TP complex in a tubular flow detector is used in a two channel flow injection set up for continuous monitoring of the drug at a frequency of 25–30 samples h−1. The results obtained with drugs containing 50–100 mg SC tablet−1 show a mean standard deviation of ±2% of the nominal which agree fairly well with data obtained by spectrophotometry.

A new sensor for anionic surfactants with a membrane consisting of 33 wt% poly(vinyl chloride) (PVC), 66 wt% dioctylphthalate (DOP) plasticizer, and 1 wt% tridodecylmethylammonium chloride (TDMAC) is developed and used for flow injection analysis. The sensor displays a working response range of 5×10−7–5×10−3 M dodecylbenzene sulfonate (DBS−) with a Nernstian slope of 58.5±0.2 mV decade−1, a response time of 30 s and a detection limit of 1.5×10−7 M DBS−. Selectivity measurements with different anionic species indicate good membrane selectivity towards DBS−. The sensor is used to measure anionic surfactants (DBS−) in different wastewater samples, commercial detergent products, and for monitoring the rate of surfactant biodegradation in sewage treatment plants. The results obtained agree fairly well with data obtained by the standard extraction-spectrophotometric method. The proposed potentiometric method offers the advantages of simplicity, accuracy, automation feasibility, and applicability to turbid and colored sample solutions.

Five poly(vinyl chloride) matrix membrane sensors responsive to some beta-blockers (atenolol, bisoprolol, metoprolol, propranolol and timolol) are described and characterized. The sensors are based on the use of the ion-association complexes of the beta-blocker cations with tungstophosphate anion as electroactive materials. The performance characteristics of these sensors, evaluated according to IUPAC recommendations, reveal fast, stable and near-Nernstian response for 10(-2)-2 x 10(-7) mol l(-1) of different beta-blockers over the pH range 2-9. Many inorganic and organic cations as well as drug excipients and diluents normally used in drug formulations do not interfere. The sensors are used for direct potentiometry of beta-blockers in some pharmaceutical preparations. Validation of the method according to the quality assurance standards shows suitability of the proposed sensors for use in the quality control assessment of these drugs. Results with an average recovery of 99.1% and a mean standard deviation of +/- 1.3% of the nominal are obtained which compare fairly well with data obtained using the British Pharmacopoeia method.

Polymeric matrix tubular membrane sensors incorporating poly(vinyl chloride) matrix, o-nitrophenyloctylether (oNPOE) plasticizer and either dinonylnaphthalene sulfonate (DNNS) or tridodecylammonium chloride (TDMAC) ionophore are prepared and electrochemically evaluated for determination of carrageenan polyion. These sensors are used for monitoring potentiometric titration of carrageenan with protamine titrant. Carrageenan at the concentration levels of 0.2 ± 1.5% (m/m) in a variety of food products (e.g., cream, chocolate, caramel, ice cream, and salad dressing) are satisfactory determined. Results agree fairly well with nominal values are obtained and confirmed by recovery experiments of spiked samples. The method has several advantages over all previously reported methods in being more simple, accurate and applicable for routine analysis of real samples without prior treatment.

Echis carinatus crude venom was fractionated into 11 protein fractions by preparative native polyacrylamide gel electrophoresis (PAGE). All fractions except fractions 5 and 10 appeared as a single band on analytical native PAGE. Purified venom fractions 1, 4, 8, 10 and 11 appeared as single bands on SDS-PAGE whereas fractions 2, 3 and 7 contained two bands and fraction 6 contained three bands. Fractions 1 and 3 exhibited basic pI (7.3 and 7.6) respectively, while fractions 2, 4, 6, 8, 10 and 11 showed an acidic pI. Amino acid analysis also showed that crude venom is rich in acidic amino acids. A significant hyperglycaemia was produced by i.p. injection of E. carinatus crude venom, after 15 min of envenomation which persisted even after 24 h. Along with hyperglycaemia there was a significant decrease of liver glycogen at 15 min and 1, 12 and 24 h. A significant decrease of plasma [pyr + lac] levels was found from 15 min to 24 h. The liver [pyr + lac] levels increased significantly after 24 h. Skeletal muscle [pyr + lac] level was significantly decreased after 24 h of envenomation. Fractions 2 and 6 produced the highest increase in plasma glucose after 12 h and fraction 7 after 24 h. The plasma insulin level was significantly decreased by these three fractions (2, 6 and 7). So it can be hypothesized that the hyperglycaemia may result from a direct effect of a venom component on plasma insulin. Fractions 7, 8 and 11 caused the highest decrease in plasma [pyr + lac] while fractions 1, 2, 3, 4 and 8 produced the most significant decrease in liver [pyr + lac]. The most significant increase in lactate dehydrogenase level was also produced by fractions 1, 2, 3, 4 and 8. Copyright © 2001 John Wiley & Sons, Ltd.

A flow injection system for the simultaneous amperometric determination of glucose and lactate is described. Glucose oxidase and lactate oxidase were immobilized, separately, into two-parallel immobilized enzyme reactors (IERs). The enzymatically produced hydrogen peroxide was detected by anodic amperometry at platinum electrodes coated with an electropolymeric-permselective layer of m-phenylenediamine to enhance the selectivity of H2O2 detection. The configuration of the flow system was designed to give a response output in the form of a train of two successive peaks. The heights of these two peaks were directly proportional to the concentration levels of glucose and lactate in the sample, respectively. The presented flow system proved to offer the advantages of i) simplicity, ii) operational stability, up to 3 months, iii) simultaneous determination of glucose and lactate using a single 20-µL sample injection iv) insensitivity of the signal of a given component by wide variations in the concentration of the second component, v) high sample throughput, more than 50 samples/hour, vi) high accuracy and precision, and vii) a reasonable dynamic range of about two-orders of magnitude. The reliability of the present system was assessed by measuring glucose and lactate simultaneously in several samples of blood plasma, urine and dairy products. The obtained results were in good agreement with those obtained by standard spectrophotometric methods.

Novel miniaturized carboxylated poly(vinyl chloride) and poly fluoro sulfonate (Nafion) matrix membrane sensors in an all-solid state graphite support were developed, electrochemically evaluated and used for the assay of verapamil drug. These sensors incorporate the native polymers without plasticizer and/or drug-ion pair complex. Upon soaking these sensors in verapamil test solution, electroactive self regenerated membranes are formed and a near-Nernstian potentiometric response is induced for verapamil over the concentration range 1×10−2–1×10−5 M with a cationic slope of 56–57 mV decade−1 of concentration. Inherent advantages of these sensors include fast response ( 6 months), good thermal stability (up to 60 °C), high sensitivity (down to 1 μg ml−1), extended working pH range (2–8) and reasonable selectivity. Verapamil could be determined in various dosage forms with an average recovery of 98.8% (st.dev. 0.8%) of the nominal concentration without any significant interferences from various excipients and diluents commonly used in drug formulations.

New, simple and convenient potentiometric, spectrofluorimetric and spectrophotometric methods are described for the determination of metformin in pharmaceutical preparations. The potentiometric technique is based on preparation of PVC membrane sensors incorporating metformin–reineckate, and metformin–tungstosilicate ion-pairs as electroactive species with dioctylphthalate and o-nitrophenyloctylether as plasticizers, respectively. A membrane consisting of carboxylated PVC plasticized with dibutylsebacate is also prepared and tested. These sensors give rapid Nernstian response for 10−1–10−5 M metformin at pH range 5–11. The metformin–tungstosilicate based sensor is used in a flow-through sandwich cell for flow injection potentiometric determination of metformin. Graphite sensors coated or doped with metformin–tungstosilicate-PVC, Cu-diethyldithiocarbamate and Ni-diethyldithiocarbamate are also prepared and used for monitoring the titration of the drug with tetraphenyl borate (TPB−), Cu2+ and Ni2+ ions, respectively. The spectrofluorimetric method depends on the reaction of metformin with chrysenequinone in alkaline medium to give a Schiff's base, which upon hydrolysis gives the free base. The latter in the presence of 1-naphthol gives a fluorescent product with excitation and emission maxima at 450 and 520 nm, respectively. The fluorescence–concentration relationship is linear over the range 20–200 μg ml−1 metformin. The proposed spectrophotometric technique involves reaction of metformin with Cu2+ in basic medium to form a Cu–metformin complex. The complex is dissolved in cyclohexylamine and its maximum absorption at 540 nm is measured. Beer's law is obeyed over the range 0.5–2 mg ml−1 metformin. Various cations, some nitrogenous compounds or drug excipients cause no interferences. Results obtained by these techniques are comparable and compare favorably with data obtained using the British Pharmacopoeia method.

Based on the condensation reaction between amino groups of either cyclophosphamide or ifosphamide with the carbonyl group of ninhydrin, giving coloured and fluorescent products, a spectrophotometric procedure for both drugs is suggested in the range from 30 to 90μg ml−1 at 564 nm, with accuracies of 100.6 ± 1.06% and 100.8 ± 1.02% for cyclophosphamide and ifosphamide, respectively. Also, a spectrophotometric procedure for both drugs is proposed in the range from 1.2 to 3.6 μg ml−1 at 465 nm and 485 nm for cyclophosphamide and ifosphamide, respectively, using 380 nm as an excitation wavelength for both drugs with accuracies of 100.4 ± 1.83% and 99.5 ± 1.64%, respectively. This condensation reaction, however, does not differentiate between the two isomeric drugs. Another new method is, therefore, suggested. It depends on the fact that the secondary amino group of ifosphamide is hindered electronically and sterically, while the nucleophilic amino group of cyclophosphamide reacts with the nitrosyl gr...

Sensitive and fast-responding potentiometric sensors are described for the determination of warfarin and ibuprofen. They consist of PVC matrix membranes containing the drag-ferroin ion-association complexes as electroactive materials and dioctylphthalate as a solvent mediator. Linear dynamic response range between 1 × 10−2 and 2 × 10−5M with Nernstian slopes of 59–60 mV/decade concentration and a detection limit of 0.8–1.3 μg/ml are obtained. A wide range of organic anions and drag excipients do not interfere. Titration of the drugs with a standard ferroin solution using either a drag-ferroin or ferroin-TPB PVC sensor in conjunction with an Ag-AgCl reference electrode displaysS-shaped titration curves with sharp potential breaks at stoichiometric 1∶2 (ferroin:drug) reaction. Differential titration curves with well-defined peaks at the equivalence points are obtained using drug-ferroin/ferroin-TPB PVC membrane sensors. Direct potentiometry and potentiotitrimetry of warfarin and ibuprofen in various pharmaceutical preparations are presented and compared. Several advantages over the pharmacopoeial methods and other techniques in current use are offered by the proposed technique.

A method for determining malathion residues by reversed- phase liquid chromatography (LC) using methanol only as mobile phase is described. Malathion [diethyl(dimethoxyphosphinothiol)succinate] was applied on marjoram, mint, and chamomile. Residues were detected in fresh and dry crops by LC and confirmed by gas-LC/mass spectrometry. Average recovery of malathion was 85%. Residues detected in fresh marjoram, mint, and chamomile were 0.18, 0.23, and 0.083 mg/kg, respectively. Residues detected in dry marjoram and mint were 0.024 and 0.050 mg/kg, respectively. No malathion residues were detected in dry chamomile. The minimum detectable concentration with this method is 0.013 mg/kg. The study suggests it is safe to use malathion up to 2 sprays per season provided the crop is harvested not less than 3 weeks from the last spray

Flow injection methods for sensitive, accurate and rapid determination of diamines, mainly putrescine (PUT) and cadaverine (CAD), and diamine oxidase (DAO) are described. Putrescine determination is based on an immobilized enzyme reactor (IER) loaded with putrescine oxidase and amperometric detection of the produced hydrogen peroxide at a platinum electrode. Putrescine oxidase (PUO) was assayed by simple injection of putrescine oxidase solution into a carrier buffer containing a fixed concentration of putrescine followed by similar detection of hydrogen peroxide. In PUT measurements peak currents were linearly related to putrescine concentration in the range from 10 μM to 1 mM with sample frequency of ∼70 samples/hour. No change in sensitivity and detection limit were observed after more than 1000 injections over a two week period. PUO was determined in the range of 50–2500 mU/ml, with sample frequency of ∼40 samples/hour. The lower detection limit of the present method (1.5 mU/ml) is suitable for determining the expected low levels of PUO in the amniotic fluid as a possible marker for premature rupture of membranes (PROM). The effects of flow rates, sample sizes, and substrate concentrations in the detection limits and assay efficiencies are given in the present work.

A novel atrazinium selective membrane sensor consisting of an atrazine phosphomolybdate ion-pair complex dispersed in a PVC matrix plasticized with dioctylphthalate is described and electrochemically evaluated under static and hydrodynamic modes of operation. The sensor is incorporated in a flow-through sandwich cell and used as a detector for flow injection determination of atrazine herbicide. The intrinsic characteristics of the detector in a low dispersion manifold is determined and compared with those of a conventional-shaped sensor. In a phosphate buffer of pH 5, the detector exhibits a rapid near-Nernstian response (52.3 mV/decade) for atrazinium cation over the concentration range 10−2 - 10−5 M. Concentrations as low as 0.3μg/ml of atrazine can be detected with an average recovery of 98.3% (mean standard deviation 0.6%), and the sample input rate is 60 sample per hour. The sensor is used for determining atrazine in herbicide formulations, and in extracts of water and soil. No interferences...

New methods are developed for the determination of cinnarizine in various dosage forms. They are based on the reaction of cinnarizinium cation with cobalt tetrathiocyanate anion, whereby a sparingly soluble blue 2∶1 drug: reagent ion-pair complex is quantitatively formed. The complex is (a) extracted with nitrobenzene and spectrophotometrically measured at 622 nm; (b) extracted with nitrobenzene and nebulized in an air-acetylene flame for atomic absorption spectrometric monitoring of cobalt at 242.5 nm; and (c) dispersed in a PVC membrane plasticized with 2-nitrophenyloctyl ether and used as a sensor for direct potentiometric determination of the drug. Optimum reaction conditions and performances of the three analytical techniques are evaluated and compared. At the 25 mg level of cinnarizine, the three methods give results with equal accuracy and precision. The average recovery is 98–99% of the nominal and the mean standard deviation is 0.7%. No significant interferences are caused by drug excipients and diluents.

The lipophilic nickel(II) and iron(II) bathophenanthroline derivatives of ethamsylate are used as ion-exchangers with high selectivity characteristics for ethamsylate. Poly(vinyl chloride) membrane sensors incorporating these electroactive materials display fast linear response for 1 × 10−1−1 × 10−4M ethamsylate under static and hydrodynamic modes of operation. In an acetate buffer of pH 4, the calibration slope is 51–53 mV/concentration decade and the lower limit of detection is 5.3 μg/ml. Except for salicylate and nitrate, most common anions, organic sulfonates, carboxylates, phenolates and various pharmaceutical excipients and diluents do not interfere. Determination of ethamsylate in various dosage forms shows an average recovery of 98.9% of the nominal and a mean standard deviation of 0.7%.

A novel, sensitive and selective enzymatic potentiometric method for the determination of SHAM drug (salicylhydroxamic acid) is described. It is based on the fast and potent inhibitory action of SHAM on urease-catalyzed urea hydrolysis. The initial rate of the urea/urease reaction is potentiometrically monitored using an ammonia gas sensor. Effects of urease activity, urea substrate concentration, incubation time, temperature and pH are demonstrated. Under optimized conditions, there is a linear relationship between the degree of enzyme inhibition and SHAM concentrations over the range 0.5–7 μg ml −1 , with a 3σ detection limit of 0.1 μg ml −1 . Determination of SHAM in some pharmaceutical preparations shows an average recovery of 98% of nominal and a mean relative standard deviation of 1%. Drug decomposition products and metabolites (salicylic acid and salicylamide) do not interfere.

A simple potentiometric method is described for mercurimetric titration of barbiturates using a solid-state iodide ion-selective electrode. The optimum titration conditions involve the use of a borate buffer of pH 9–10 as a medium and mercury(II) perchlorate of pH 1.7–1.9 as a titrant. Under these conditions, titration curves with two sharp consecutive inflection breaks are obtained. The first inflection corresponds to quantitative and stoichiometric reaction of barbiturates with mercury(II) and the second break is due to the reaction of the buffer with the titrant. No interferences are caused by Cl−, Br−, PO4 3- and many excipients and diluents commonly used in the drug formulations. Determination of barbiturates in various pharmaceutical preparations gives reproducible results with an average recovery of 99.1% of the nominal (st.dev. 0.3 %) and the method offers significant advantages over the titrimetric method of the British Pharmacopoeia.

New, simple and convenient potentiometric and spectrophotometric methods are described for the determination of ranitidine. The potentiometric technique is based on direct measurements of the drug cation with novel PVC matrix membrane sensors incorporating ranitidine-reineckate, tungstophosphate and tungstosilicate ion association complexes as electroactive compounds with 2-nitrophenyl phenyl ether as plasticizing solvent mediator. These sensors exhibit rapid near-Nernstian stable responses for 10−2 − 10−6 M ranitidine over the pH range 4–8, and are used in a flow-through sandwich cell for flow injection determination of the drug. The spectrophotometric method involves the formation of a yellow di(N-nitroso)ranitidine chromophore by reaction of ranitidine with excess nitrite in acetate buffer of pH 4.8 and in the presence of Cu 2+ Br − or micelles as catalyst. Beer's law is obeyed at 450 nm over the range 0.3–12 mg ml−1. Determination of ranitidine in a variety of pharmaceutical dosage forms using the proposed potentiometric and spectrophotometric methods shows an average recovery of 98.4% of the nominal values and a mean standard deviation of 0.5%. No interferences are caused by various drug excipients and diluents. The results compare favourably with those obtained by the liquid Chromatographic method of the US Pharmacopoeia.

The construction and general performance characteristics of four novel potentiometric PVC membrane sensors responsive to the cinnarizinium cation are described. These sensors are based on the use of the ion-association complexes of the cinnarizinium cation with tetraphenylborate, flavianate, reineckate and 12-molybdatophosphate counter anions as ion exchange sites in a plasticized PVC matrix. These sensors exhibit fast, stable and near-Nernstian response for the doubly charged cinnarizinium cation over the concentration range 10 −2 to 10 −6 M and pH 2–3. No interferences are caused by many inorganic and organic cations. Direct potentiometric determination of 4 400 μg ml −1 cinnarizine shows an average recovery of 99.5% and a mean standard deviation of ±0.5%. The sensors proved useful for determining cinnarizine in various dosage forms, monitoring tablet dissolution rates and testing tablet uniformity. The results compare favourably with data obtained by liquid chromatography.

A simple, accurate and selective method is described for the determination of morphine in illicit powders, based on monitoring the initial rate of fluoride ion liberation from the reaction of morphine with 1-fluoro-2,4-dinitrobenzene at pH 9 and 35 °C, using a solid-state fluoride ion-selective electrode. Under optimized reaction conditions, as little as 15 μg/ml of morphine is determined with an average recovery of 99.5% and a mean relative standard deviation of 1.2%. Determination of morphine in real illicit powders containing 6–18% morphine gives results comparing favorably with those obtained from isocratic reverse-phase high-performance liquid chromatography. No interferences are caused by many structurally related and associated compounds such as codeine, acetylcodeine, ethylmorphine, acetylmorphine and diacetylmorphine (heroin).

Residues of dicofol and pirimiphos-methyl applied at different rates on strawberry and common beans, respectively, were monitored at different intervals. The rate of crop production of each rate was also studied. High-performance liquid chromatography was employed to detect both compounds and gas chromatography/mass spectrometry analysis was conducted for further confirmation. All tested rates produced residue levels below the respective maximum residue limits (MRL) of dicofol and pirimiphos-methyl. The highest two rates of dicofol (185 and 139 g of active ingredient/feddan) and of pirimiphos-methyl (750 and 562 g of active ingredient/feddan) produced comparable production rates of strawberry and common beans, respectively. Dicofol residues were 0.230 and 0.105 mg/kg, 1 and 2 weeks, respectively, after the application of the highest rate. The highest rate of pirimiphosmethyl produced a residue level of 0.399 mg/kg, 1 week after application.

A novel potentiometric assay method for arylsulfatase enzyme is described based on measuring the initial reaction rate of hydrolysis of 4-nitrocatechol sulfate (4-NCS) substrate under optimized conditions. A monitoring sensor incorporating a PVC membrane with a nickel(II) bathophenanthroline-4-NCS ion-pair complex as electroactive material and 2-nitrophenyl phenyl ether as solvent mediator is developed and characterized. the sensor exhibits fast and stable linear response for 8×10 -3 -7.5×10 -6 M 4-NCS with an anionic slope of 58.5±0.2 mV/decade over the pH range 3-6. The sensor is used to follow up the decrease in a fixed concentration of 4-NCS (2×10 -4 M) as a function of arylsulfatase activity at pH 5.6 and 37 o C. A linear relationship between the initial rate of substrate hydrolysis and enzyme activity holds for 0.2-2.4 IU/mL (SD 2%). Activity measurement of arylsulfatase enzyme isolated from camel liver gives results that compare favorably well with data obtained using the standard spectrophotometric assay method. Significant advantages over many of the previously described spectroscopic methods are offered by the proposed potentiometric technique

A phosphodiesterase I (EC 3.1.4.1; PDE-I) was purified from Walterinnesia aegyptia venom by preparative native polyacrylamide gel electrophoresis (PAGE). A single protein band was observed in analytical native PAGE and sodium dodecyl sulfate (SDS)-PAGE. PDE-I was a single-chain glycoprotein with an estimated molecular mass of 158 kD (SDS-PAGE). The enzyme was free of 5'-nucleotidase and alkaline phosphatase activities. The optimum pH and temperature were 9.0 and 60°C, respectively. The energy of activation (Ea) was 96.4, the V(max) and K(m) were 1.14 µM/min/mg and 1.9 × 10(-3) M, respectively, and the K(cat) and K(sp) were 7 s(-1) and 60 M(-1) min(-1) respectively. Cysteine was a noncompetitive inhibitor, with K(i) = 6.2 × 10(-3) M and an IC(50) of 2.6 mM, whereas adenosine diphosphate was a competitive inhibitor, with K(i) = 0.8 × 10(-3) M and an IC(50) of 8.3 mM. Glutathione, o-phenanthroline, zinc, and ethylenediamine tetraacetic acid (EDTA) inhibited PDE-I activity whereas Mg(2+) slightly potentiated the activity. PDE-I hydrolyzed thymidine-5'-monophosphate p-nitrophenyl ester most readily, whereas cyclic 3'-5'-AMP was least susceptible to hydrolysis. PDE-I was not lethal to mice at a dose of 4.0 mg/kg, ip, but had an anticoagulant effect on human plasma. These findings indicate that W. aegyptia PDE-I shares various characteristics with this enzyme from other snake venoms.

The effects of the pesticide on some enzyme systems (transaminases and oxidoreductases) and quality attributes of tomato fruits were also studied. The results showed that the GC-ECD analysis allowed an accurate determination of profenofos residues. GC-MS analysis was less susceptible to interfering compounds than the GC-ECD analysis. In addition, the GC-MS technique allowed the identification of the studied pesticide and ensured that profenofos extraction and cleanup steps were acceptable. The fresh tomatoes had considerable amounts of profenofos depending on the time from pesticide application

Methods are described for the determination of amitriptyline, imipramine and orphenadrine in some antidepressant drugs. They are based on a prior reaction with ammonium reineckate to form 1∶1 water-insoluble drugreineckate ion-pair complexes. These complexes are (i) used as ion-exchangers in liquid-membrane electrodes responsive to the drug cations, (ii) extracted with nitrobenzene or dissolved in acetonitrile and spectrophotometrically measured at 525 nm and (iii) dissolved in 90% acetone followed by nebulization in an air-acetylene flame for atomic absorption spectrometric measurements of Cr at 358.6 nm. The reaction and monitoring conditions are optimized to permit determination of as little as 10 μg/ml of the drugs. Determination of the drugs in some pharmaceutical preparations shows an average recovery of 98.8% of the nominal and a mean standard deviation of 0.8%. The results compare favorably with data obtained by the United States and British Pharmacopoeia methods.

The construction of liquid membrane and PVC matrix-type cocainium ion selective electrodes and their use for direct potentiometry and potentiometric titration of cocaine are described. The ion-pair complexes of cocaine cation with reineckate and tetraphenylborate anions are either dissolved in nitrobenzene solvent or dispersed in a PVC matrix, with DOP or DBS plasticizer, and used as the ion-exchange membranes. The electrochemical response characteristics of electrodes incorporating these types of membranes are evaluated with regard to the effect of pH, foreign basic compounds, temperature and γ-radiation. The electrodes display a stable fast Nernstian response for 10 −2 -10 −5 M cocainium cation over the pH range 3–7, the lower limit of detection being 1 μg/ml. Determination of as low as 20 μg/ml cocaine hydrochloride shows an average recovery of 98% and a mean standard deviation of ±0.6%. The electrodes exhibit useful analytical characteristics for determining cocaine in some illicit powders. The results agree fairly well with those obtained by gas-liquid chromatography.

Simple methods are described for the determination of ethambutol in pharmaceutical preparations. They are based on the reaction of the drug with copper phosphate suspension in a borate buffer of pH 9.2, whereby a blue 1∶1 water-soluble copper-ethambutol complex is quantitatively formed. Four portions of the reaction solution are used for (i) measurement of copper by atomic-absorption spectrometry at 324.7 nm; (ii) potentiometric titration with EDTA with use of a solid-state copper ion-selective electrode; (iii) visual titration with EDTA (copper-PAN indicator); and (iv) spectrophotometric measurement of the copper-ethambutol complex at 640 nm. The results obtained are in good agreement and are better than those of the British Pharmacopoeia (BP) method.

Two types of polyvinyl chloride (PVC) matrix membrane electrodes responsive to the antimalarial drug chloroquine have been constructed, electrochemically evaluated, compared, and used in pharmaceutical analysis. Type 1 is the classic PVC model with chloroquine-tetraphenylborate (TPB) sensor; Type 2 is a coated silver disk without internal filling solution. Both electrode types exhibited rapid linear potentiometric response to the logarithmic concentration of diprotonated chloroquine cation in the 10−1–10−6M range with calibration slopes 28-30 mV/concentration decade over the pH range 1.8-6.2. These electrodes were sensitive enough to permit determination of chloroquine phosphate at concentrations as low as 5 μg/mL with good accuracy and precision. Determination of chloroquine in various pharmaceutical preparations using direct potentiometry and potentiometric titration with NaTPB gave an average recovery of 98.8% of the nominal values (SD 0.5%). The Type 2 electrode was also assessed in a flow-through sandwich cell for flow injection analysis. Results were compared with data obtained by the U.S. Pharmacopeia method.

A highly sensitive and selective method is described for the determination of microgram quantities of water in nonaqueous organic solvents. The method is based on the reaction of water with N, N′-carbonyldiimidazole at ambient temperature in anhydrous quinoline solvent whereby one mole of carbon dioxide gas is instantaneously and stoichiometrically liberated per mole of water. The released gas is absorbed in NaOH and monitored with a CO2 gas sensor. The method is applicable for determination of 2 pg-20 nig H2O/ml of various organic solvents. The average recovery is 99% and the mean standard deviation being 0.5%. The method displays several advantages over the standard Karl Fischer procedure.

Construction and characterization of potentiometric membrane sensors for quantification of diclofenac and warfarin drugs are described. The membranes of the sensors incorporate 1.8 wt.% iron(II)-phthalocyanine (Pc) as a molecular recognition reagent, 64.3 wt.% dibutylsebacate (DBS) solvent mediator, 1.8 wt.% tridodecylmethylammonium chloride (TDMAC) as membrane additive and 32.1 wt.% poly(vinyl chloride) (PVC) as a matrix. The sensors display linear response for 1 × 10 −2 to 9 × 10 −6 mol l −1 (detection limit 5.4 × 10 −6 mol l −1 ) and 1 × 10 −2 to 5 × 10 −6 mol l −1 (detection limit 3 × 10 −6 mol l −1 ) with anionic slopes of −61 ± 1 and −63 ± 1 mV decade −1 over the pH range 5.5–9 for declofenac and warfarin, respectively. Validation of the assay methods according to the quality assurance standards confirms their suitability for quality control purposes. Use of the sensor for the assay of various formulations of the drugs shows a mean average recovery of 99.7% of the nominal values and a mean precision of ±0.3%. Significantly improved accuracy, precision, response time, stability, selectivity and sensitivity are offered by these simple and cost-effective potentiometric sensors compared with other standard techniques.

Two novel potentiometric membrane sensors responsive to the ibuprofen drug have been developed. These incorporate poly(vinyl chloride) and polyurethane matrix membranes containing 5,10,15,20-tetraphenylporphrinato (TPP) indium(II) ionophore plasticized with dibutylsebacate. The sensors show a near-Nernstian response with anionic slopes of -53 and -55 mV decade(-1), over the concentration range of 4.2 x 10(-6)-1.0 x 10(-2) and 3.3 x 10(-6)-1.0 x 10(-2) M ibuprofen within pH ranges of 4-9 and 5-9 for PVC and PU matrix membranes, respectively. A sensor based on a polyurethane membrane displays a lower detection limit and a wider linear working range, and a sensor based on a PVC membrane exhibits a better overall selectivity, especially in the presence of lipophilic organic anions. Both sensors are used for the quantification and quality-control assessment of ibuprofen in pharmaceutical preparations. The average recoveries are 99.1+/-0.3% and 99.3+/-0.3% for TPP In(III)-PVC and TPP In(III)-PU based membrane sensors, respectively. High selectivities towards ibuprofen in the presence of many anions, drug excipients and diluents are offered by both sensors, which exhibit a non-Hofmeister selectivity pattern.

New high performance liquid chromatography (HPLC) and thin layer densitometry (TLC) methods are developed for quantification of cinnarizine in dosage forms in the presence of its photo-degradation products and related substances and in the presence of its metabolites in serum. Mobile phases consisting of benzene–methanol–formic acid (80:17:3) and methanol–acetate buffer of pH 4 (70:30) are satisfactorily used for resolution of cinnarizine from associated substances by TLC and HPLC techniques, respectively. The lower detection limits are 16 and 10 ng μl −1 of cinnarizine with standard deviations of 1.3 and 1.1% with TLC and HPLC, respectively. The methods are used for assessment of drug purity, stability, bioavailability, bioequivalency and tablet dissolution rate. Four cinnarizine related substances and six drug degradation products are isolated and identified by infrared and mass spectrometry. The results obtained by both techniques are in good agreement and offer the advantages of reproducibility and accuracy.

Three reliable spectrophotometric and spectrofluorimetric procedures are described for the determination of fluorouracil in bulk powder and ampoules in the presence of its degradation products. One spectrophotometric procedure, based on measurement at 555 nm of the violet-coloured complex formed by fluorouracil with cobalt(II), has a detection limit of 0.03 mg mL−1. Two sensitive spectrofluorimetric procedures are also proposed. One is based on measurement of the intrinsic fluorescence of the liberated fluorouracil at 375 nm, after precipitation as its cobalt(II) complex, decomposition of the precipitate with sulphuric acid and excitation at 295 nm. The second depends on excitation of the fluorouracil-cobalt(II) complex at 395 nm and measuring its fluorescence at 483 nm. The limits of detection of the two spectrofluorimetric procedures are 0.5 and 2 μg mL−1, respectively. The three procedures have been used successfully for the determination of fluorouracil ampoules. The validity of the methods has been assessed by applying the standard addition technique.

New thin layer densitometry and high performance liquid chromatography (HPLC) methods are described for quantitative determination of glafenine in dosage forms in the presence of its photo-degradation products and in serum in the presence of its metabolites. Mobile phases consisting of toluene-isopropyl alcohol-dimethylformamide-water (18:3:1:0.5) and methanol-water-phosphoric acid (80:120:0.5) are found to be efficient for reasonable separation and adequate resolution of glafenine from associated substances by thin layer chromatography (TLC) and HPLC techniques, respectively. The methods are used for the study of glafenine purity, stability, bioavailability, bioequivalence and tablet dissolution rate. The results obtained by TLC and HPLC techniques are in good agreement and offer the advantages of reproducibility and accuracy.

In this paper, fabrication, characterization, and physiological application of a miniaturized amperometric lactate biosensor are described. The sensor is based on cross-linked lactate oxidase and tetrathiafulvalene-tetracyano-quinodimethane (TTF-TCNQ) charge transfer complex. The sensor was developed for continuous quantitative measurement of the lactate accumulation in ischemic myocardium under severe depletion of oxygen. The sensor was evaluated in vitro at an applied potential of 0.15 V vs Ag/AgCl; it proved to combine all the performance characteristics desired for the present application, such as proper response in absence of oxygen, good operational stability, good accuracy and precision (103.5 +/- 1.2%), adequate response time (t95% = 80 s), and wide linear dynamic range up to 27 mM (r = 0.9998) in N2-saturated solutions and at 37 degrees C. The prepared sensors (n = 12) showed sensitivity of 380 +/- 90 nA/mM, and a background current of 240 +/- 50 nA. The lower limit of detection is 0.4 +/- 0.15 mM with a S/N ratio equal to 3. Results obtained for direct lactate monitoring in ischemic rabbit papillary muscle under no-flow conditions and PO26 mm Hg are presented.

The potentiometric response characteristics of a poly(vinyl chloride) membrane electrode for heroin based on its ion-pair complex with tetraphenylborate were examined. The influence of pH, temperature and time on the performance of the electrode system was investigated. The electrode shows a near-Nernstian response over the heroin concentration range 10(-2)-10(-4) M with good precision. The mean relative standard deviation for the determination of heroin in 40 micrograms ml-1(-1) mg ml-1 aqueous heroin hydrochloride solutions is 1.2%. The electrode exhibits good selectivity for heroin in the presence of a number of adulterants and basic organic compounds commonly present in illicit heroin powders. The method was applied to the direct potentiometric determination of heroin in illicit powders (10-36% heroin) and the results agreed fairly well with those obtained by gas - liquid chromatography.

A novel plastic membrane ion-selective electrode for determining the diclofenac anion is described. The sensing membrane of the electrode consists of diclofenac-nickel(II) bathophenanthroline as an ion-exchanger site in a poly(vinyl chloride) matrix plasticized with o–nitrophenyl phenyl ether. In borate buffer solutions of pH 8–12, the electrode exhibits a fast, stable and linear response for 1 × 10–2–5 × 10–5 mol dm–3 diclofenac with an anionic slope of 55.1 ± 0.2 mV decade–1 at 25 °C. Potentiometric selectivity measurements revealed negligible interferences from 14 different anions including aromatic and aliphatic carboxylic acid salts. The electrode displays useful analytical characteristics for the direct determination of diclofenac in various pharmaceutical preparations. Results with an average recovery of 98 ± 0.6% of the nominal value were obtained.

A new, simple, accurate and rapid method is described for the determination of total penicillins in pharmaceutical preparations. The method is based on desulphurization with potassium plumbite whereby one mole of lead sulphide is formed per mole of penicillin. The excess of lead ions is titrated with EDTA at pH 4.5, with use of the lead ion-selective electrode. Results are reproducible within ± 0.5% and compare favourably with those obtained by the procedures of the United States and British Pharmacopoeias.

Simple, rapid, selective, and sensitive spectrophotometric methods are described for manual and semiautomated determination of vitamin K3. These methods are based on reactions with piperidine and malononitrile whereby intense red and blue colors with maximum absorption at 510 nm (E1%1cm 150) and 580 nm (E1%1cm 155), respectively, are developed. The reactions are sensitive enough to permit the determination of 2-100 μg vitamin K3/mL with an average recovery of 98% and a standard deviation of 1%. There is no interference from vitamins K1 and K2, and the reduced forms of K vitamins, or from many common pharmaceutical diluents and additives.

A detailed spectrophotometric study of the reaction of estrogens and androgens with 98% sulphuric acid at 20° C and of the effect of various dilutions with water on the nature of the spectra is presented. Dilution of the androgens-acid and estrogens-acid solutions with water to 40% and 80% v/v acid, respectively, increases the absorption intensity 3 to 11 times. The optimum conditions for determination of down to 2μg/ml of estrone, estradiol, ethinylestradiol, testosterone, and rostanalone and progesterone are reported. The results show a relative standard deviation of +-1.5 %.