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BACKGROUND: One diagnosis of cystic fibrosis involves measuring the nasal transepithelial potential difference (NPD) as a complementary technique in the forms of the disease, where the sweat test is non-discriminating. The NPD is measured using solutions with and without chlorides, containing a variety of substances whose activities on nasal mucus membranes are studied or assessed. Among the solutions described in the literature and used in specialized centers, none seems to be best adapted for industrial production for reasons of stability (formulas of the international consensus of Rowe et al. and formulas of Knowles et al.) and/or potential toxicity (formulas of Middleton et al.). OBJECTIVE(S): Defining new formulas, according to those of the international consensus, with greater physicochemical and microbiological stability. METHODS: The reformulation tests were conducted on the formulas of Rowe et al., using CHESS® (CHemical Equilibrium of Species and Surfaces) software for modeling aqueous systems that substantially reduced the number of experiments. CHESS® software was first validated using models of ideal and non-ideal solutions. Thereafter, experimentation was carried out for the sake of comparison with theoretical data. RESULTS: CHESS® software using models of ideal and non-ideal solutions were validated. The experimentation confirmed the theoretical data, and new formulas were assessed based on their physicochemical (pH, content, Osmolality) and microbiological stability. CONCLUSION: The new formulas defined here guarantee excellent physicochemical and microbiological stability of diagnostic solutions, indispensable criteria for harmonizing and comparing results from different specialized centers using NPD measurements. These new formulas apply to the harmonization approach of techniques for measuring the nasal transepithelial potential difference.
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Fibrosis Quística , Fibrosis Quística/diagnóstico , Regulador de Conductancia de Transmembrana de Fibrosis Quística , Humanos , Mucosa Nasal , Programas Informáticos , SudorRESUMEN
INTRODUCTION: In the context of current distrust of antimicrobial preservatives, the quantities of these substances in two pharmaceutical formulas were studied: an ophthalmic solution of cysteamine preserved benzalkonium chloride at 1mg/5mL and Glycerotone(®) preserved with sorbic acid at 0.1g/100g. The purpose of this work was to verify that a reduction of the quantities of preservative continues to fulfil the requirements for antimicrobial preservation. MATERIAL AND METHODS: The Test of efficacy of antimicrobial preservation, section 5.1.3 of the 8th edition of the European Pharmacopoeia, was carried out on each formulation prepared with decreasing quantities of preservative. RESULTS: The results show that formulations whose preservative concentration was reduced by a factor of four remained compliant with standards. It is to be noted that in formulas without preservative, fungal growth was observed in both the solution of Glycerotone(®) and the ophthalmic solution containing cysteamine. DISCUSSION: Although there is no question that an antimicrobial preservative is necessary, the quantity of preservative can be reduced without deteriorating the quality of the pharmaceutical product but the minimal effective concentration remains to be determined. CONCLUSION: The formulations of many pharmaceutical products should therefore be examined in order to limit the quantities of preservative while continuing to guarantee patient's safety.
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Antiinfecciosos Locales/química , Cisteamina/farmacología , Glicerol/farmacología , Soluciones Oftálmicas/química , Conservadores Farmacéuticos/farmacología , Bacterias/efectos de los fármacos , Compuestos de Benzalconio/administración & dosificación , Compuestos de Benzalconio/química , Química Farmacéutica , Cisteamina/química , Contaminación de Medicamentos/prevención & control , Hongos/efectos de los fármacos , Glicerol/química , Pruebas de Sensibilidad Microbiana , Conservadores Farmacéuticos/química , Ácido SórbicoRESUMEN
Raman microspectroscopy has been shown to enable the identification of micro-particles inside sealed glass containers for pharmaceutical use without any sample preparation. Raman spectra were collected from unknown particles with a maximum size of 1mm, adsorbed on the inner surface of ampoules. The particles were clearly identified as primarily hematite with traces of magnetite by their characteristic Raman spectral bands. The presence of this deposit was attributed to the projection of iron oxides during the manufacturing process. These oxide particles were not detected by the quality control process of the glass manufacturer, showing that in-process quality controls failed to detect this problem. Particle identification by Raman microspectroscopy appears to be a selective, rapid and reliable analytical procedure for quality control and assurance in the pharmaceutical industry. Identification of the particles was also helpful for evaluating the nature of the contaminant and enables consequences for the toxicological aspects of final product quality to be managed.
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Embalaje de Medicamentos , Compuestos Férricos/análisis , Vidrio/química , Soluciones Farmacéuticas , Tecnología Farmacéutica , Adsorción , Soluciones Cardiopléjicas , Contaminación de Medicamentos/prevención & control , Microquímica/métodos , Tamaño de la Partícula , Control de Calidad , Espectrometría Raman , Propiedades de SuperficieRESUMEN
A simple and sensitive method is described for the determination of platinum surface contamination originating from cisplatin, carboplatin and oxaliplatin. Following extraction from swabs and preconcentration with the cloud point extraction (CPE) method, detection was by graphite furnace atomic absorption spectrometry (GFAAS). After desorption of platinum compounds from the swab, CPE involved on preconcentration of platinum in aqueous solution with diethyldithiocarbamate (DDTC) as chelating agent and Triton X-114 as extraction medium. DDTC is not only a chelating agent, but may also be a good candidate for the inactivation of platinum compounds. DDTC is recommended by the Word Health Organization (WHO) for the destruction of platinum-based anticancer drugs. The main factors affecting CPE efficiency, pH of the sample solution, concentrations of DDTC and Triton X-114, equilibration temperature and incubation time, were evaluated in order to enhance sensitivity of the method. The desorption of platinum compounds from the swab was investigated in parallel. Since platinum is bound to DDTC, it must exchange with copper in order to enhance platinum atomizing by GFAAS. A preconcentration factor of 29 was obtained for 10 mL of a platinum solution at 10 microg mL(-1). In optimal conditions, the limit of detection was 0.2 ng mL(-1), corresponding to 2.0 ng of platinum metal on the swab. Absorbance was linear between 0.7 and 15 ng mL(-1). The proposed method was applied for the determination of surface contamination by platinum compounds with correct results.
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Descontaminación/métodos , Platino (Metal)/análisis , Espectrofotometría Atómica/métodos , Carboplatino/análisis , Precipitación Química , Cisplatino/análisis , Ditiocarba , Octoxinol , Compuestos Organoplatinos/análisis , Oxaliplatino , Compuestos de Platino/análisis , PolietilenglicolesRESUMEN
Solid organ transplantation is an increasing need and a well-established activity which requires maintaining the quality of the transplant from procurement through the entire, storage, transport and graft procedure. Solutions for organ preservation play a key role in this procedure, by minimizing the deleterious effects of both ischemia and reperfusion. As such, their qualitative and quantitative compositions have to be optimized and validated. The development strategy and formulations proposed for these solutions are analyzed in this review as well as the results of the clinical studies which have set up the relevant pharmacological and physicochemical criteria. The French regulatory status of these products is also discussed. A clear distinction has to be made between solutions for organ preservation which are classified as produits thérapeutiques annexes (therapeutic ancillary products) and cardioplegic liquid formulations which are considered as medicinal products and are subject to marketing approval. Finally, the roles of the hospital pharmacist in the evaluation, selection, purchase and proper use of these products are described.
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Soluciones Cardiopléjicas/química , Soluciones Preservantes de Órganos/química , Química Farmacéutica , Composición de Medicamentos , Humanos , Farmacéuticos , Servicio de Farmacia en Hospital , Daño por Reperfusión/fisiopatología , Daño por Reperfusión/prevención & control , Trasplante/efectos adversosRESUMEN
There is a monography of Triethylenetetramine dichlorhydrate (Trientine) in the United States Pharmacopeia. But neither the base nor the salts di- or tetra-chlorhydrate are in the European Pharmacopeia. Triethylène tetramine tetrachlorhydrate, used by AGEPS now as matural, is more soluble then triethylene tetramine dichlorhydrate. It is administred to patients with Wilson's disease, which results from a congenital lack of the copper metabolism. A quantitative purity test of this drug by automated multiple development high-performance thin-layer chromatography is developed and validated. The validation parameters tested are specifically characterized by retention factor, linearity, limits of detection and quantitation of several nanograms, reliability, and accuracy. To determine impurities, the monography of triethylenetetramine dichlorhydrate in the American Pharmacopeia is tested. This method in classic developing tank requires two mobile phases and is not quantitative. Assays in high-performance liquid chromatography with a different column and mobile phase did not give good results for the separation of impurities. Thus, it is not possible to perform comparative validation of the separation of the impurities. Only the assay of triethylenetetramine with potentiometer detection has been validated.
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Trientina/análisis , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
A simple detection system with a high-performance liquid chromatography (HPLC) with positive ionisation-tandem mass spectrometry (ESI-MS/MS) for determining diphemanil methylsulphate (DMS) levels in human plasma using 4-diphemanylmethylene,1-methylpiperidine as an internal standard (I.S.), is proposed. The acquisition was performed with the multiple reactional monitoring (MRM) mode, by monitoring the transitions: m/z 278>262 for DMS and m/z 263>247 for the I.S. The method involved a simple single-step deproteinisation with acetonitrile. The analyte was chromatographed on a Zorbax C18 reversed-phase chromatographic column by isocratic elution with 10(-3)M ammonium acetate and 10(-3)M hexafluorobutyric acid, adjusted to pH 7.0 with ammoniac/acetonitrile (40/60, v/v). The results were linear over the studied range (0.5-50.0 ng mL(-1)) and the total analysis time for each run was 10 min. The mean extraction apparent recoveries expressed at the 95% intervals of confidence were 94-104% for DMS and 92-106% for the I.S. The intra- and inter-assay precisions were 4.6-8.4% and 2.9-10.6%, respectively. The limit of quantification was 0.15 ng mL(-1). The devised assay was successfully applied to the residual concentrations monitoring in infant.
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Cromatografía Líquida de Alta Presión/métodos , Piperidinas/sangre , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masas en Tándem/métodos , Humanos , Lactante , Piperidinas/uso terapéutico , Reproducibilidad de los ResultadosRESUMEN
3,4-Diaminopyridine is used to treat some symptoms met in Lambert-Eaton myasthenia syndrome. It was shown efficient to reduce a form of variable muscle weakness and fatigability typical of the disease and correlated to a block of acetylcholine release. In France, 3,4-diaminopyridine is nowadays given to patients under capsules form and the status of hospital preparation. Whatever the diluant used in the formulation, the stability period could not exceed 12 months. Preliminary studies were made on a salt form in order to test the influence of various stress factors and determine if there is interaction between them. From this study, the most influent stress condition, presence of hydrogen peroxide, was selected and a comparative study was performed to compare the stability of molecular and salt species. Solutions of each species were exposed to 5 or 15% of hydrogen peroxide and analyzed at 8, 24, 72 and 216 h of degradation by HPLC-UV. Fractions of detected impurities were purified and collected by semi-preparative HPLC-UV and analyzed by HPLC-UV-ESI-MS and IR spectroscopy in order to determine their structure hypotheses. Theses experiments demonstrate that the salt species were more stable under oxidative stress condition than molecular species. The two main degradation products were collected and identified as 4-amino, 3-nitropyridine and 3,4-diaminopyridine-N-oxide when the molecular form was degraded whereas only 4-amino, 3-nitropyridine was found in less quantity in the salt solutions. Nitrogen pyridine and pyridine amine could not easily be oxidized by hydrogen peroxide in salt comparatively to molecular species due to the lone pair of electron engaged in a bound with hydrogen in the first case and by resonance change of the pyridine in the second case. This modification of structure promoted different pathways of degradation for the salt form which are more dependent of energy. Owing to the better stability of the salt species, a new pharmaceutical form containing it was developed to assess its stability under ICH standard conditions allowing an industrial manufacture of this drug.
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4-Aminopiridina/análogos & derivados , 4-Aminopiridina/análisis , Amifampridina , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Peróxido de Hidrógeno/química , Indicadores y Reactivos , Cinética , Estándares de Referencia , Espectrometría de Masa por Ionización de Electrospray , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
Despite constant improvement in the control of interactions between packaging materials and food, the problem remains worrisome. The theoretical study of various type of reactions (absorption, migration, permeation) as well as influential factors are described. The analysis of the French regulation is detailed with a special focus on the January 2003 order. After the description of assay protocols using simulated fluids, the main issues are studied and the future of manufacturing processes and materials is presented.
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Contaminación de Alimentos/análisis , Embalaje de Alimentos/legislación & jurisprudencia , Plásticos/análisis , Absorción , Contaminación de Alimentos/legislación & jurisprudencia , Francia , PermeabilidadRESUMEN
In order to quantify a small amount of a drug, 3,4-diaminopyridine (3,4-DAP), in animal plasma samples, an analytical method was developed. It involved an extraction of 3,4-DAP and phenylephrine, used as internal standard (IS), from plasma with solid-phase extraction (SPE) on C18 cartridges. This analytical method is a hyphenated technique based on high-performance liquid chromatography with electrochemical detection (HPLC-EC) whose purpose is to obtain first a sensitive method and second a satisfying separation between 3,4-DAP and phenylephrine. The analytical method is accurate, specific, and linear between 10 and 500 g of 3,4-DAP per litre. The recovery of 3,4-DAP is estimated at 70.8% with a 95% confidence interval of (66.0 -75.6%). Intermediate precision was evaluated on three quality control samples; the intra-day precision was estimated at 13.5, 9.1, 7.8% and the inter-day precision at 17.9, 8.4, 9.3%. The limit of quantification of the method was evaluated at 10 g l-1. First toxicokinetic parameters determined on dogs plasma samples after one 3,4-DAP oral administration of 1 mg kg-1 were: Cmax=395.7 microg l-1; Tmax =15 min; t1/2=113.6 min; Clearance/F=16.8 ml kg-1 min-1 and Vd/F=2.7 l kg -1.
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4-Aminopiridina/análogos & derivados , 4-Aminopiridina/sangre , Cromatografía Líquida de Alta Presión/métodos , Electroquímica/métodos , Amifampridina , Animales , Perros , Femenino , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Diphemanil methylsulfate (DMS) is a synthetic antimuscarinic agent classically used in infants for vagal hypertonia-related symptoms. A normal-phase, isocratic liquid chromatographic method was developed for the quantitative determination of DMS in bulk drugs and in pharmaceutical forms. The method has been completely validated and robustness of this method has been studied. The limit of detection (LOD) for DMS impurities namely, impurity 1 and 2 were found to be 11 and 46 ng/ml. The limit of quantitation (LOQ) was found to be 49 and 139 ng/ml for impurity 1 and 2, respectively. The stability studies have been performed for 2 and 10 mg DMS tablets subjected at various temperatures: 25 degrees C (long term storage condition) and 40 degrees C (accelerated storage condition) for 18 and 6 months, respectively. At 25 degrees C, the samples were found to be stable for the study period. At 40 degrees C, 2 and 10 mg DMS tablets showed degradation up to 5 and 10% over a 6-month period.
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Antagonistas Muscarínicos/análisis , Piperidinas/análisis , Algoritmos , Cromatografía Líquida de Alta Presión , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Reproducibilidad de los Resultados , Comprimidos , Temperatura , Factores de TiempoRESUMEN
An off-line system is proposed consisting of ion-pair reversed-phase liquid chromatography, collections of fractions at the outflow of the column and furnace atomic absorption spectrometry. The so-called system allowed determination of both arsenic and selenium species mainly found in the environment and in mammals (arsenite, arsenate, monomethylarsonate, dimethylarsinate, selenite, selenate, selenocystamine, selenocystine, selenomethionine and selenoethionine). In order to study the retention behaviour of these compounds and to estimate the optimal conditions for the chromatographic separation, central composite designs were used to evaluate the influence of the eluent parameters such as pH, tetrabutylammonium phosphate (TBA) concentration and sodium hydrogenphosphate amounts. The retention factors of each species and the selectivity were established as response criteria. Response surfaces and isoresponse curves were drawn from the mathematical models and enabled one to determine the optimal conditions and to visualise the method robustness. The predicted optimal zone was situated at pH 5.5-6.5, 4.0 mM Na2HPO4 and 3.0-4.0 mM TBA. Regression models suggested linearity for the studied compounds in the range 25-200 microg selenium and arsenic per litre investigated.
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Arsénico/química , Cromatografía Liquida/métodos , Selenio/química , Espectrofotometría Atómica/métodos , Concentración de Iones de Hidrógeno , Compuestos de Amonio Cuaternario/químicaRESUMEN
Central composite designs (CCDs) were used in the study of the ion-pair chromatographic separation of arsenic and selenium species in tap water: monomethylarsonate, dimethylarsinate, selenomethionine and selenite. The ternary eluent consisted of tetrabutylammonium phosphate (TBA), sodium hydrogenphosphate (Na2HPO4) and 1% acetonitrile. CCD allowed the investigation of the influence of the eluent parameters, which varied from 0.5 to 4.2 mmol l-1 Na2HPO4, 0.5 to 4.2 mmol l-1 TBA and pH 4.9 to 8.2, on the capacity factors (k') of arsenic and selenium compounds. Furthermore, another mathematical model that permitted the variation of the chromatographic selectivity of species, computed from their retention data to be followed, was investigated. This showed the ability to locate the optimum conditions within the experimental design, so that arsenic and selenium species could be simultaneously quantified with good efficiency and resolution. A comparison between the predicted and the experimental response values was made in order to assess the prediction quality of the model. Response surfaces and isoresponse curves obtained from the mathematical models allowed the determination of the optimum chromatographic conditions and the robustness of the method. The predicted optimum zone allowing satisfactory determination of both arsenic and selenium compounds was pH 5.5-6.5, 2.5 mmol l-1 Na2HPO4 and 3.0-4.0 mmol l-1 TBA.
RESUMEN
Methacholine chloride is a powerful cholinergic bronchoconstrictor agent used during bronchial airway hyper-responsiveness diagnosis. Methacholine is susceptible to hydrolysis in aqueous solutions in acetic acid and beta-methylcholine. In the present work, kinetics of hydrolysis with different solvents (water and phosphate-buffered saline (PBS) pH 7.4) at different temperatures have been studied using a newly developed high-performance liquid chromatography. At 4 degrees C, kinetic determination of hydrolysis in methacholine chloride solutions (50 mg/ml) shows no hydrolysis in either aqueous or phosphate-buffered solutions over a 40-day period. At 30 degrees C, concentration of unbuffered methacholine chloride solutions remained unchanged, but buffered methacholine chloride solutions have degradation up to 5.5% over a 40-day period. At 40 degrees C, concentration of unbuffered methacholine chloride has degradation up to 5% and buffered methacholine chloride solutions have degradation up to 10% over a 40-day period. Methacholine chloride solutions are susceptibly to be used in hospital pharmacy at different concentrations. We have studied pH and osmolality for methacholine solutions prepared with different diluents potentially used in hospital pharmacies, i.e. deionized water, 0.9% NaCl and PBS pH 7.4. We have demonstrated that methacholine solutions prepared with deionized water at 50 mg/ml and diluted with PBS pH 7.4 from 5 to 40 mg/ml are isoosmotic and potentially available for inhalation tests to measure non-specific bronchial hyper-responsiveness.
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Broncoconstrictores/química , Cromatografía Líquida de Alta Presión/métodos , Cloruro de Metacolina/química , Soluciones/química , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Cinética , Concentración Osmolar , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Hydride generation inductively coupled plasma-atomic emission spectrometry (HG ICP-AES) was used as a continuous detection system for the determination of arsenic in the eluate from a high-performance liquid chromatographic (HPLC) system. Four arsenic species [arsenite As(III), arsenate As(V), monomethylarsonate (MMA), and dimethylarsinate (DMA)] present in the urine samples of patients treated intravenously with arsenite, were analyzed separately by HPLC-HG-ICP-AES using a non-polar C18 column. This analytical method allowed the sensitive determination of the arsenic species in the submicrogram per liter range. Urine samples collected on different days after arsenite administration were found to contain arsenite predominantly--monomethylarsonate and dimethylarsinate were also detected.
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Arsénico/orina , Arsenicales/farmacocinética , Óxidos/farmacocinética , Trióxido de Arsénico , Arsenicales/administración & dosificación , Calibración , Cromatografía Líquida de Alta Presión , Cisteína/química , Humanos , Indicadores y Reactivos , Inyecciones Intravenosas , Óxidos/administración & dosificación , Reproducibilidad de los Resultados , Soluciones , Espectrofotometría AtómicaRESUMEN
A convenient, reliable and rapid method for determination of total cysteamine in human plasma by high-performance liquid chromatography with fluorescence detection is reported. This assay involves reduction of samples with dithiothreitol, derivatization of total cysteamine by addition of monobromobimane and protein precipitation by perchloric acid. The calibration curve was linear in the range 2-150 nmol ml-1 and the detection limit was 0.5 nmol ml-1. This method was successfully applied for a pharmacokinetic study of three cysteamine derivatives in healthy volunteers without any interference from coexisting substances.
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Cromatografía Líquida de Alta Presión/métodos , Cisteamina/sangre , Disponibilidad Biológica , Cisteamina/farmacocinética , Disulfuros/química , Humanos , Oxidación-Reducción , Reproducibilidad de los Resultados , Espectrometría de FluorescenciaRESUMEN
BACKGROUND AND OBJECTIVE: Morphine hydrochloride, a major analgesic drug, is being increasingly administered using portable disposable infusion devices. The objective of this study was to investigate the stability of morphine in such a system at two concentrations (2.50 and 5.00 mg/ ml) over a 30-day period. METHOD: High-performance liquid chromatography of stored morphine solutions. RESULTS: The best stability was observed with disposable infusion devices filled with a morphine solution containing sodium metabisulphite as a preservative. No breakdown products were detected after 1 month of storage at room temperature, in light or darkness. On the other hand, 2.50 and 5.00 mg/ml morphine solutions without sodium metabisulphite, stored in the infusion device led to the formation of 0.205% and 0.235% of pseudomorphine, respectively, after 6 days of storage in the light, and 1.50% and 0.94% after 30 days storage. CONCLUSION: Morphine hydrochloride solutions stored in disposable infusion devices degraded very slowly, particularly when preserved with sodium metabisulphite. The solutions are stable over 5 days, the maximum period of storage normally required when using disposable infusers.
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Analgésicos Opioides/administración & dosificación , Morfina/administración & dosificación , Analgésicos Opioides/química , Equipos Desechables , Estabilidad de Medicamentos , Almacenaje de Medicamentos , Bombas de Infusión , Luz , Morfina/química , Conservadores Farmacéuticos/química , Sulfitos/químicaRESUMEN
This paper describes a new calibration method for headspace chromatographic assay of carbon monoxide, hydrogen cyanide and ethylene oxide. The calibration method is based on the in situ formation of gas in a closed system in order to avoid, the dangerous handling of pure gas or harmful substances. In the first method, the standardization is based on the in situ formation of carbon monoxide by the reaction of hot concentrated sulfuric acid with formic acid. In the second method, the standardisation is based upon the in situ reduction of ethyl thiocyano by dithiothreitol to produce HCN. In the third method, the standardisation is based upon the in situ chemical transformation of 2-chloro-ethanol into ethylene oxide with a recovery of about 60%.
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Monóxido de Carbono/sangre , Cromatografía de Gases/normas , Óxido de Etileno/sangre , Cianuro de Hidrógeno/sangre , Estándares de Referencia , EspectrofotometríaRESUMEN
This work compares two different methods for assaying hydrogen cyanide, a spectrophotometric method and a headspace gas chromatographic method, each with its own reference standard generation. In the first method, the reference standards are cyanide solutions. In the second method, the reference standards are based upon the in situ reduction of ethyl thiocyanate by dithiothreitol to produce hydrogen cyanide. Furthermore, hydrogen cyanide concentration in the blood of patients who were poisoned by smoke inhalation or who committed suicide by cyanide ingestion is determined using both methods. Results are discussed using statistical comparison.
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Cromatografía de Gases/métodos , Cianuros/análisis , Espectrofotometría Ultravioleta/métodos , Calibración , Cianuros/sangre , Ditiotreitol/química , Humanos , Cianuro de Hidrógeno/sangre , Cianuro de Hidrógeno/química , Cianuro de Hidrógeno/envenenamiento , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tiocianatos/químicaRESUMEN
Although renal-failure-related hyperphosphataemia can be corrected by various phosphate binders, there remains a need for safer and more efficient formulations to precipitate phosphate. This work describes both a theoretical approach and a phosphate precipitation test in order to design efficient binding calcium salts formulations. The results show that the combination of a soluble calcium salt (the gluconolactate) and a proton-consuming calcium salt (the carbonate) can precipitate phosphate effectively. Furthermore, the theoretical computations correlate well with the ability of the salt to bind phosphate in vitro.