Determination of nicotine and nicotine metabolites in urine by hydrophilic interaction chromatography-tandem mass spectrometry: Potential use of smokeless tobacco products by ice hockey players.

Consumption of nicotine in the form of smokeless tobacco (snus, snuff, chewing tobacco) or nicotine-containing medication (gum, patch) may benefit sport practice. Indeed, use of snus seems to be a growing trend and investigating nicotine consumption amongst professional athletes is of major interest to sport authorities. Thus, a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the detection and quantification of nicotine and its principal metabolites cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide in urine was developed. Sample preparation was performed by liquid-liquid extraction followed by hydrophilic interaction chromatography-tandem mass spectrometry (HILIC-MS/MS) operated in electrospray positive ionization (ESI) mode with selective reaction monitoring (SRM) data acquisition. The method was validated and calibration curves were linear over the selected concentration ranges of 10-10,000 ng/mL for nicotine, cotinine, trans-3-hydroxycotinine and 10-5000 ng/mL for nicotine-N'-oxide and cotinine-N-oxide, with calculated coefficients of determination (R(2)) greater than 0.95. The total extraction efficiency (%) was concentration dependent and ranged between 70.4 and 100.4%. The lower limit of quantification (LLOQ) for all analytes was 10 ng/mL. Repeatability and intermediate precision were ?9.4 and ?9.9%, respectively. In order to measure the prevalence of nicotine exposure during the 2009 Ice Hockey World Championships, 72 samples were collected and analyzed after the minimum of 3 months storage period and complete removal of identification means as required by the 2009 International Standards for Laboratories (ISL). Nicotine and/or metabolites were detected in every urine sample, while concentration measurements indicated an exposure within the last 3 days for eight specimens out of ten. Concentrations of nicotine, cotinine, trans-3-hydroxycotinine, nicotine-N'-oxide and cotinine-N-oxide were found to range between 11 and 19,750, 13 and 10,475, 10 and 8217, 11 and 3396, and 13 and 1640 ng/mL, respectively. When proposing conservative concentration limits for nicotine consumption prior and/or during the games (50 ng/mL for nicotine, cotinine and trans-3-hydroxycotinine and 25 ng/mL for nicotine-N'-oxide and cotinine-N-oxide), about half of the hockey players were qualified as consumers. These findings significantly support the likelihood of extensive smokeless nicotine consumption. However, since such conclusions can only be hypothesized, the potential use of smokeless tobacco as a doping agent in ice hockey requires further investigation.

Determination of chlorzoxazone and 6-hydroxychlorzoxazone in plasma by gas chromatography--mass spectrometry.

A gas chromatographic-mass spectrometric method is presented which allows the determination of chlorzoxazone and 6-hydroxychlorzoxazone after derivatization with the reagent N-tert.-butyldimethylsilyl-N-methyltrifluoroacetamide. No interference was observed from endogenous compounds following the extraction of plasma samples from six different human subjects. The standard curves were linear over a working range of 20 to 4000 ng/ml and of 20 to 1000 ng/ml for chlorzoxazone and 6-hydroxychlorzoxazone, respectively. Recoveries ranged from 65 to 97% for the two compounds and intra- and inter-day coefficients of variation were always less than 9%. The limit of quantitation of the method was found to be 5 ng/ml for the two compounds, hence allowing its use for single low dose pharmacokinetics.

A fatal overdose of cocaine associated with coingestion of marijuana, buprenorphine, and fluoxetine. Body fluid and tissue distribution of cocaine and its metabolites determined by hydrophilic interaction chromatography-mass spectrometry(HILIC-MS).

Chromatographic separation of highly polar basic drugs with ideal ionspray mass spectrometry volatile mobile phases is a difficult challenge. A new quantification procedure was developed using hydrophilic interaction chromatography-mass spectrometry with turbo-ionspray ionization in the positive mode. After addition of deuterated internal standards and simple clean-up liquid extraction, the dried extracts were reconstituted in 500 microL pure acetonitrile and 5 microL was directly injected onto a Waters Atlantis HILIC 150- x 2.1-mm, 3-microm column. Chromatographic separations of cocaine, seven metabolites, and anhydroecgonine were obtained by linear gradient-elution with decreasing high concentrations of acetonitrile (80-56% in 18 min). This high proportion of organic solvent makes it easier to be coupled with MS. The eluent was buffered with 2 mM ammonium acetate at pH 4.5. Except for m-hydroxy-benzoylecgonine, the within-day and between-day precisions at 20, 100, and 500 ng/mL were below 7 and 19.1%, respectively. Accuracy was also below +/- 13.5% at all tested concentrations. The limit of quantification was 5 ng/mL (%Diff < 16.1, %RSD < 4.3) and the limit of detection below 0.5 ng/mL. This method was successfully applied to a fatal overdose. In Switzerland, cocaine abuse has dramatically increased in the last few years. A 45-year-old man, a known HIV-positive drug user, was found dead at home. According to relatives, cocaine was self-injected about 10 times during the evening before death. A low amount of cocaine (0.45 mg) was detected in the bloody fluid taken from a syringe discovered near the corpse. Besides injection marks, no significant lesions were detected during the forensic autopsy. Toxicological investigations showed high cocaine concentrations in all body fluids and tissues. The peripheral blood concentrations of cocaine, benzoylecgonine, and methylecgonine were 5.0, 10.4, and 4.1 mg/L, respectively. The brain concentrations of cocaine, benzoylecgonine, and methylecgonine were 21.2, 3.8, and 3.3 mg/kg, respectively. The highest concentrations of norcocaine (about 1 mg/L) were measured in bile and urine. Very high levels of cocaine were determined in hair (160 ng/mg), indicating chronic cocaine use. A low concentration of anhydroecgonine methylester was also found in urine (0.65 mg/L) suggesting recent cocaine inhalation. Therapeutic blood concentrations of fluoxetine (0.15 mg/L) and buprenorphine (0.1 microg/L) were also discovered. A relatively high concentration of Delta(9)-THC was measured both in peripheral blood (8.2 microg/L) and brain cortex (13.5 microg/kg), suggesting that the victim was under the influence of cannabis at the time of death. In addition, fluoxetine might have enhanced the toxic effects of cocaine because of its weak pro-arrhythmogenic properties. Likewise, combination of cannabinoids and cocaine might have increase detrimental cardiovascular effects. Altogether, these results indicate a lethal cocaine overdose with a minor contribution of fluoxetine and cannabinoids.

Nous processos i formes de creixement urbà: el cas del districte industrial de Montebelluna a Itàlia

This article analyses the spatial organization of Montebelluna's industrial district (Italy) as an exemple of the dinamics of urbanization phenomenon in small urban areas. The study is divided in two parts: in the first one I present the social organisation's model of production named «industrial district» and its relation with the space, which is characterizeded by the rising of diffused urbanization settlements; in the second part I try to verify some explanatory factors pointed out by different autors in this specific area with an historical analysis of processes point of view. The diffused organisation of economic and housing activity show a change in the urban morphology

El concepte de districte industrial: un repàs des de l'òptica de la tradició italiana

L’ article fa un repàs de l’evolució del concepte de districte industrial des de l’ òptica de l’experiència italiana. Partint de la constatació dels canvis que hi ha hagut en les formes d’organització de la producció en els tres darrers decennis, s’exposa l’evolució del model del districte industrial com a paradigma d’ Alfred Marshall, de principis del segle XX, s’ha anat enriquint a mesura que ha madurat l’ experiència districtual, que avui afronta els reptes de la globalització econòmica

Accuracy profile validation of a new method for carbon monoxide measurement in the human blood using headspace-gas chromatography-mass spectrometry (HS-GC-MS).

The aim of our study was to provide an innovative headspace-gas chromatography-mass spectrometry (HS-GC-MS) method applicable for the routine determination of blood CO concentration in forensic toxicology laboratories. The main drawback of the GC/MS methods discussed in literature for CO measurement is the absence of a specific CO internal standard necessary for performing quantification. Even if stable isotope of CO is commercially available in the gaseous state, it is essential to develop a safer method to limit the manipulation of gaseous CO and to precisely control the injected amount of CO for spiking and calibration. To avoid the manipulation of a stable isotope-labeled gas, we have chosen to generate in a vial in situ, an internal labeled standard gas ((13)CO) formed by the reaction of labeled formic acid formic acid (H(13)COOH) with sulfuric acid. As sulfuric acid can also be employed to liberate the CO reagent from whole blood, the procedure allows for the liberation of CO simultaneously with the generation of (13)CO. This method allows for precise measurement of blood CO concentrations from a small amount of blood (10 μL). Finally, this method was applied to measure the CO concentration of intoxicated human blood samples from autopsies.

Refrigeració de les gillettes d’ una talladora industrial

L’empresa Proslit Equipment forma part del Grup Comexi i la seva activitat consisteix en la fabricació de màquines talladores de material flexible. Degut als avenços tecnològics, s’han incrementat les prestacions de les seves màquines, entre altres coses, s’ha augmentat la velocitat de tall del film fins a 800 m/min. Aquest factor afegit a condicionants com per exemple treballar amb materials gruixuts i abrasius, a temperatures ambientals elevades, etc. fa que sorgeixi una problemàtica en el tall gillette. Degut a la fricció entre el film que circula i les gillettes que el tallen, es crea una energia calorífica que fa augmentar la temperatura de les gillettes fins a tal extrem que aquestes provoquen petites fusions del plàstic, aquest s’incrusta a les gillettes que s’acaben trencant. L’objecte principal d’aquest projecte és fer una anàlisi tècnica mitjançant elements finits de la problemàtica que s’ha detectat a les màquines talladores de l’empresa Proslit Equipment, concretament de l’escalfament de les gillettes utilitzades en el sistema de tall. Es pretén crear un model teòric que s’aproximi al màxim a la realitat de manera que es pugui observar el comportament tèrmic del sistema de tall en funció de les condicions que es determinin com a més desfavorables. Una vegada s’obtinguin aquests resultats teòrics, es valoraran i es proposaran solucions

Use of accuracy profile for the validation of a gas chromatography-negative chemical ionization tandem mass spectrometry method: quantification of ethyl glucuronide in hair

Introduction: Ethylglucuronide (EtG) is a direct and specific metabolite of ethanol. Its determination in hair is of increasing interest for detecting and monitoring alcohol abuse. The quantification of EtG in hair requires analytical methods showing highest sensitivity and specificity. We present a fully validated method based on gas chromatography-negative chemical ionization tandem mass spectrometry (GC-NCI-MS/MS). The method was validated using French Society of Pharmaceutical Sciences and Techniques (SFSTP) guidelines which are based on the determination of the total measurement error and accuracy profiles. Methods: Washed and powdered hair is extracted in water using an ultrasonic incubation. After purification by Oasis MAX solid phase extraction, the derivatized EtG is detected and quantified by GC-NCI-MS/MS method in the selected reaction monitoring mode. The transitions m/z 347 / 163 and m/z 347 / 119 were used for the quantification and identification of EtG. Four quality controls (QC) prepared with hair samples taken post mortem from 2 subjects with a known history of alcoholism were used. A proficiency test with 7 participating laboratories was first run to validate the EtG concentration of each QC sample. Considering the results of this test, these samples were then used as internal controls for validation of the method. Results: The mean EtG concentrations measured in the 4 QC were 259.4, 130.4, 40.8, and 8.4 pg/mg hair. Method validation has shown linearity between 8.4 and 259.4 pg/mg hair (r2 > 0.999). The lower limit of quantification was set up at 8.4 pg/mg. Repeatability and intermediate precision were found less than 13.2% for all concentrations tested. Conclusion: The method proved to be suitable for routine analysis of EtG in hair. GC-NCI-MS/MS method was then successfully applied to the analysis of EtG in hair samples collected from different alcohol consumers.

Urinary analysis of 16(5alpha)-androsten-3alpha-ol by gas chromatography/combustion/isotope ratio mass spectrometry: implications in anti-doping analysis.

We present a method for the analysis of urinary 16(5alpha)-androsten-3alpha-ol together with 5beta-pregnane-3alpha,20alpha-diol and four testosterone metabolites: androsterone (Andro), etiocholanolone (Etio), 5alpha-androstane-3alpha,17beta-diol (5alphaA), 5beta-androstane-3alpha,17beta-diol (5betaA) by means of gas chromatography/combustion/isotopic ratio mass spectrometry (GC/C/IRMS). The within-assay and between-assay precision S.D.s of the investigated steroids were lower than 0.3 and 0.6 per thousand, respectively. A comparative study on a population composed of 20 subjects has shown that the differences of the intra-individual delta(13)C-values for 16(5alpha)-androsten-3alpha-ol and 5beta-pregnane-3alpha,20alpha-diol are less than 0.9 per thousand. Thereafter, the method has been applied in the frame of an excretion study following oral ingestion of 50 mg DHEA initially and oral ingestion of 50mg pregnenolone 48 h later. Our findings show that administration of DHEA does not affect the isotopic ratio values of 16(5alpha)-androsten-3alpha-ol and 5beta-pregnane-3alpha,20alpha-diol, whereas the isotopic ratio values of 5beta-pregnane-3alpha,20alpha-diol vary by more 5 per thousand upon ingestion of pregnenolone. We have observed delta(13)C-value changes lower than 1 per thousand for 16(5alpha)-androsten-3alpha-ol, though pregnenolone is a precursor of the 16-ene steroids. In contrast to 5beta-pregnane-3alpha,20alpha-diol, the 16-ene steroid may be used as an endogenous reference compound when pregnenolone is administered.

Finca-Museo agroindustrial San Julián : proyecto para la difusión y la conservación del patrimonio industrial de Guatemala

Disseny d'un espai multidisciplinar que permeti l'interpretació del Patrimoni Industrial i Cultural de la Finca agroindustrial de San Julián (Guatemala), amb l'objectiu de fomentar la difusió i la conservació del Patrimonio Industrial del país

Projecte de nau industrial sostenible

La majoria de naus industrials són edificis contenidors, senzills, modulars i, sobretot, concebuts com a edificis rendibles, sense tenir en compte criteris de protecció del medi ambient. En el projecte s’ha optat per fer el disseny i càlcul d’una nau industrial prefabricada de formigó armat per a la fabricació de maquinària per la indústria agroalimentària, amb dos nivells d’oficines, zona de producció amb pont grua, laboratoris i magatzems amb una superfície total aproximada de 1800 m². Per tal que sigui un edifici sostenible, s’ha optat per la instal·lació de plaques solars fotovoltaiques, aïllament tèrmic, aprofitament d’aigües plujanes, gestió de residus, aprofitament òptim, il·luminació natural, estalvi d’energia a causa d'una bona gestió dels recursos energètics

Projecte constructiu d’una nau industrial

Definició d’una nau industrial per a magatzem frigorífic mitjançant lamemòria tècnica, els plànols i els càlculs ubicada al terme municipal de Begur (Baix Empordà)

Gestió d'un magatzem recanvis industrial

El treball final de carrera tracta l'estudi i disseny de la gestió d'un magatzem, en particular enfocat a un magatzem de recanvis d'una empresa de caire industrial, que a banda d'utilitzar els materials per a realitzar el manteniment dels equips productius també els necessita per a la construcció d'automatismes per a la automatització del procés productiu. L'estudi esta enfocat a una posterior parametrització e implementació mitjançant SAP R/3, ja que aquest ERP és una de les eines més potents que existeixen al mercat mundial per la gestió de magatzems, amb el valor afegit d'integrar el sistema de emmagatzematge amb la resta de àrees funcionals de l'empresa.

Evaluation of work-related volatile organic compounds (VOCs) exposition in automotive painting cabins industrial cleanings

Automotive painting cabins are cleaned with several solvents, being great part of them mixtures of volatile organic compounds (VOCs), where the three xylene isomers are the most important constituents. To evaluate the work-related exposition of the cleaners that use these mixtures of solvents, xylenes have been determined in the working ambient air as well as its metabolite, o-m-p-methyl hippuric acid, has been analysed in urine to establish the dermal and respiratory exposition. This evaluation has been done in order to assess the occupational exposure to VOCs and to know the working conditions of the cleaners, but also to evaluate the effectiveness of personal protective equipment (PPE), the engineering control and the work practices.The xylenes have been chosen as indicators of exposition because they are the main components in the cleaning solvents used, with a level of concentration between 50% and 85%.The Xylenes have an occupational exposure limit (8 h TWA) of 50 ppm (221 mg/m3) and a short-term exposure limit (STEL) of 100 ppm (442 mg/m3). On the other hand, the biological exposure index (BEI) for xylenes is the sum of the total methyl hippuric acids in urine at the end of the work-shift, being the value 1500 mg/g creatinine.

Dashboard industrial: panell d'indicadors per gestionar una fàbrica d'una multinacional del sector d'automoció

En el context de globalització i competitivitat actuals, sobretot en el sectord’automoció, les diferències competitives entre empreses o companyies estàcada vegada més relacionada amb els factors immaterials, tals com elconeixement, la investigació, el desenvolupament tecnològic i la qualificaciódels recursos humans i l’eficiència en la gestió.L’eficiència en la gestió és bàsica per aconseguir un plus de competitivitatque és clau per satisfer els clients, i per tant, també per agilitzar lesorganitzacions i posar-les a punt per a nous reptes i per a nous models denegoci per donar resposta a la demanda de la canviant i exigent societat.Aquest treball exposa un exemple d’un sistema de gestió basat en el panelld’indicadors (“Dashboard Industrial”) per una planta d’una multinacional delsector d’automoció.Aquesta eina, que està alineada amb l’estratègia de la companyia, es potextrapolar altres empreses i a altres sectors. Està basada en lametodologia PDCA (Plan Do Check Act) és a dir planificant objectius,posant-los en pràctica mesurant-los periòdicament i prenent decisions per lamillora contínua dels resultats de cada una dels indicadors.Sens dubte, l’eficiència en la gestió és un dels factors clau per lesorganitzacions amb ànim innovador i competitiu.En el treball també es destaca la importància que té la tasca dels enginyersen la gestió al llarg de la seva vida laboral.