Determination of total and inorganic mercury in whole blood by cold vapor inductively coupled plasma mass spectrometry (CV ICP-MS) with alkaline sample preparation

A simple method with a fast sample preparation procedure for total and inorganic mercury determinations in blood samples is proposed based on flow injection cold vapor inductively coupled plasma mass spectrometry (FI-CVICP-MS). Aliquots of whole blood (500 mL) are diluted 1 + 1 v/v with 10.0% v/v tetramethylammonium hydroxide (TMAH) solution, incubated for 3 h at room temperature and then further diluted 1 + 4 v/v with 2.0% v/v HCl. The inorganic Hg was released by online addition of L-cysteine and then reduced to elemental Hg by SnCl(2). On the other hand, total mercury was determined by on-line addition of KMnO(4) and then reduced to elemental Hg by NaBH(4). Samples were calibrated against matrix-matching. The method detection limit was found to be 0.80 mu g L(-1) and 0.08 mu g L(-1) for inorganic and total mercury, respectively. Sample throughput is 20 samples h(-1). The method accuracy is traceable to Standard Reference Material (SRM) 966 Toxic Metals in Bovine Blood from the National Institute of Standards and Technology (NIST). For additional validation purposes, human whole blood samples were analyzed by the proposed method and by an established CV AAS method, with no statistical difference between the two techniques at 95% confidence level on applying the t-test.

Determination of mitragynine in rat plasma by LC-MS/MS: Application to pharmacokinetics

This study used for the first time LC-MS/MS for the analysis of mitragynine (MIT), a mu-opioid agonist with antinociceptive and antitussive properties, in rat plasma. Mitragynine and the internal standard (amitriptyline) were extracted from plasma with hexane-isoamyl alcohol and resolved on a Lichrospher (R) RP-SelectB column (9.80 and 12.90 min, respectively). The quantification limit was 0.2 ng/mL within a linear range of 0.2-1000 ng/mL The method was applied to quantify mitragynine in plasma samples of rats (n = 8 per sampling time) treated with a single oral dose of 20 mg/kg. The following pharmacokinetic parameters were obtained (mean): maximum plasma concentration: 424 ng/mL; time to reach maximum plasma concentration: 1.26 h; elimination half-life: 3.85 h, apparent total clearance: 6.35 L/h/kg, and apparent volume of distribution: 37.90 L/kg. (C) 2009 Elsevier B.V. All rights reserved.

Benzodiazepine use and associated factors in elderly in the city of Dourados, MS, Brazil

ABSTRACT Objective The use of benzodiazepines (BZD) and associated factors in the elderly of Dourados, MS, Brazil was investigated. Methods This is a cross-sectional population-based study using a multistage sampling design. Participants were 1,022 individuals aged 805; 60 years. Measurements socioeconomic status, schooling, demographic aspects, marital status, physical activity, hospitalizations, self-rated health, use of alcohol beverages and smoking were assessed by standard questionnaire. The drugs used were obtained by checking the prescription or package and classified according to the Anatomical Therapeutic Chemical Index. Chi-square test, Chi-square for linear tendency, Fisher's exact test and Poisson regression were used to assess association between variables. Results The prevalence of use of BZD was 6.5% (CI95%: 5.1-8.2%). The oldest group (PR: 1.60 for 70-79 years and PR: 1.79 for 805; 80 years), non-use of alcohol (PR: 4.14) and use of antidepressants (PR: 8.73) were the statistically associated characteristics. Conclusions The prevalence of use of BZD in the study population was low, similar to findings of more recent Brazilian studies and lower than those obtained in international studies. The prevalence of use of BZD increased with aging and use of antidepressants.

Chirality in the new generation of antidepressants: stereoselective analysis of the enantiomers of mirtazapine, N-demethylmirtazapine, and 8-hydroxymirtazapine by LC-MS.

Mirtazapine is an antidepressant that acts specifically on noradrenergic and sertonergic receptors. A LC-MS method was developed that allows the simultaneous analysis of the R-(-)- and S-(+)-enantiomers of mirtazapine (MIR), demethylmirtazapine (DMIR), and 8-hydroxymirtazapine (8-OH-MIR) in plasma of MIR-treated patients. The method involves a 3-step liquid-liquid extraction, an HPLC separation on a Chirobiotic V column, and MS detection in electrospray mode. The limit of quantification (LOQ) for all enantiomers was 0.5 ng/mL, and the intra- and interday CVs were within 3.3% to 11.7% (concentration ranges 5-50 ng/mL). A method is also presented for the quantitative analysis of glucuroconjugated MIR and 8-OH-MIR. S-(+)-8-OH-MIR is present in plasma mainly as its glucuronide. Preliminary data suggest that in all patients, except in those comedicated with CYP2D6 inhibitors such as fluoxetine and thioridazine, R-(-)-MIR concentrations were higher than those of S-(+)MIR. Moreover, fluvoxamine seems also to inhibit the metabolism of MIR. Therefore, this method seems to be suitable for the stereoselective assay of MIR and its metabolites in plasma of patients comedicated with MIR and other drugs for routine and research purposes.

Prevalence and persistence of gymnodimines in clams from the Gulf of Gabes (Tunisia) studied by mouse bioassay and LC-MS/MS

In this work we studied the toxicity in clams from the Gulf of Gabes, Tunisia (Southern Mediterranean). Samples from two stations (M2 and S6) were collected monthly from January 2009 to September 2010, and analyzed by the official control method of mousse bioassay (MBA) for lipophilic toxins. All samples were also analyzed with the LC-MS/MS method for the determination of lipophilic toxins, namely: okadaic acid group, pectenotoxins, yessotoxins and azaspiracids, spirolides and gymnodimines (GYMs). The results showed prevalence of GYMs since it was the only toxin group identified in these samples with a maximum of 2,136 μg GYM -A kg-1 (February 2009 at M2). Furthermore, GYMs showed persistence in the area, with only one blank sample below the limit of detection. Interestingly, this blank sample was found in June 2009 after an important toxic episode which supports the recent findings regarding the high detoxification capability of clams, much faster than that reported for oysters. In comparison, good agreement was found among MBA, the LD50 value of 80-100 μg kg-1 reported for GYM- A, and quantitative results provided by LC-MS/MS. On the contrary to that previously reported for Tunisian clams, we unambiguously identified and quantified by LC-MS/MS the isomers GYM- B/C in most samples. Phytoplankton identification and enumeration of Karenia selliformis usually showed higher densities at site M2 than S6 as expected bearing in mind toxin results, although additional results would be required to improve the correlation between K. selliformis densities and quantitative results of toxins. The prevalence and persistence of GYMs in this area at high levels strongly encourages the evaluation of the chronic toxic effects of GYMs. This is especially important taking into account that relatively large quantities of GYMs can be released into the market due to the replacement of the official control method from mouse bioassay to the LC-MS/MS for lipophilic toxins (Regulation (EU) No 15/2011), and the lack of Regulation for this group of toxins.

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.

Fractura de cadera en el anciano : proceso asistencial integrado

Reemplazado por "Fractura de Cadera. Proceso Asistencial Integrado", 2014 (http://hdl.handle.net/10668/1584). Publicado en la página web de la Consejería de Igualdad, Salud y Políticas Sociales: www.juntadeandalucia.es/salud (Consejería de Igualdad, Salud y Políticas Sociales/ Profesionales / Nuestro Compromiso por la Calidad / Procesos Asistenciales Integrados)

Motivo de consulta más frecuente del paciente oncológico hospitalizado en el Hospital de Sagunto. Estudio descriptivo.

Estudi descriptiu dels principals motius d´ingrés i símptomes més freqüents del pacient oncològic. S´obtenen dades demogràfiques, clíniques i patològiques del pacient; així com el principal motiu d´ingrés i la simptomatologia que associa. Resultats: El principal motiu d´ingrés han estat les complicacions derivades de la neoplàsia (84 %), sent el dolor mal controlat la principal causa. La simptomatologia més prevalent ha estat l´anorèxia (69 %), dolor (60 %) i la perduda de pes (40 %). El dolor va ser considerat el símptoma principal, no obstant això, el 60 % dels pacients que presentaven dolor, estava mal o molt mal controlat (EVA>4).

Biomasa de las especies pelágicas más abundantes e importantes del mar peruano en el invierno 2001

La biomasa se determino por el método de estratificación, en áreas isoparalitorales de 10x30’. Se utilizaron los programas ECHOVIEW, MAPINFO Y EXCEL para el procesamiento de datos.

Perdas por erosão e rendimentos de soja e de trigo em diferentes sistemas de preparo de um latossolo roxo de Dourados (MS)

Avaliaram-se as perdas de solo e de água por erosão, em um latossolo roxo muito argiloso, com 0,03 m m-1 de declividade, da área experimental da Embrapa-Centro de Pesquisa Agropecuária do Oeste, em Dourados (MS), entre junho de 1987 e maio de 1995. Os tratamentos, aplicados antes da semeadura de trigo e de soja, cultivados em sucessão, foram: (i) escarificação + gradagem niveladora (ES), (ii) gradagens pesada + niveladora (GP), (iii) plantio direto (PD) e (iv) aração com arado de discos + duas gradagens niveladoras, sem cobertura vegetal (DE). O preparo de solo e a semeadura foram realizados no sentido do declive. O PD foi o tratamento mais eficiente, tanto no controle de perdas de solo e de água quanto em rendimentos de grãos de soja e de trigo. As perdas médias de solo e de água por erosão, relativas aos sistemas PD, ES, GP e DE, foram, respectivamente, de: 0,8; 2,8; 5,3 e 7,3 t ha-1 ano-1 e 27, 80, 112 e 149 mm ano-1. O PD, quando comparado ao DE, controlou 89% das perdas de solo e 82% das de água. O PD mostrou rendimentos médios de grãos, tanto de soja como de trigo, 17% superiores aos do GP. O ES apresentou rendimentos médios 5% superiores em soja e 12% superiores em trigo, quando comparados aos do GP. Este último, dos tratamentos cultivados, foi o menos eficaz, seja no controle à erosão, seja nos rendimentos de soja e trigo. O fator erosividade, R, foi estimado em 6.411 MJ mm ha-1 h-1 ano-1, e a erodibilidade, K, foi de 0,0045 t h MJ-1 mm-1. Entre junho/94 e maio/95, o período de maior intensidade de perdas por erosão por unidade de tempo foi do preparo de solo à semeadura da soja, e o de maiores perdas absolutas foi o de 30 a 60 dias após a semeadura dessa cultura. Isso demonstra a importância de adequada cobertura do solo, entre novembro e março, e reforça a recomendação do Sistema de Plantio Direto para a região de Dourados (MS).

Variabilidade espacial de atributos físicos em um Latossolo Vermelho distrófico sob semeadura direta em Selvíria (MS)

Em uma paisagem natural, os solos apresentam ampla variação de propriedades morfológicas, físicas, químicas e mineralógicas, resultante da superposição dos diversos fatores de formação envolvidos. No caso de uma paisagem cultivada, existem outras fontes de heterogeneidade no solo devidas ao manejo exercido pelo homem. O conhecimento dessa variação é importante para o levantamento e classificação dos solos, desenvolvimento de esquemas de amostragem e definições de práticas de manejos. O presente trabalho foi realizado em agosto e setembro de 1999, na Fazenda Experimental de Ensino e Pesquisa da Faculdade de Engenharia de Ilha Solteira/UNESP, localizada em Selvíria (MS), com o objetivo de estudar a variabilidade espacial de alguns atributos físicos de um Latossolo Vermelho distrófico, cultivado no sistema de semeadura direta. A amostragem do solo foi realizada de acordo com um desenho apropriado para a análise geoestatística na forma de uma malha em uma área de 150 m de comprimento, na direção sul, e 30 m de largura, na direção norte, totalizando 103 pontos eqüidistantes de 10 em 10 m e 39 pontos eqüidistantes de 1 m distribuídos aleatoriamente pela malha. De cada ponto definido pela malha, retiraram-se amostras nas profundidades de 0,00-0,05 m e 0,15-0,20 m. Os dados foram avaliados primeiramente por uma análise estatística exploratória, calculando-se a média, distribuição de freqüência, variância, coeficiente de variação, coeficiente de assimetria e coeficiente de curtose. Posteriormente, a dependência espacial foi verificada por meio de semivariogramas. Os atributos microporosidade, porosidade total e densidade do solo seguiram a distribuição normal, enquanto a macroporosidade e a resistência à penetração seguiram a distribuição lognormal. A umidade do solo apresentou uma distribuição mais próxima da lognormal. Os maiores coeficientes de variação foram observados para a macroporosidade e resistência à penetração, tendo as demais variáveis apresentado coeficiente de variação abaixo de 10%. Foi observada uma dependência espacial moderada para todas as variáveis estudadas. O alcance da dependência espacial variou de 8,36 m (umidade do solo) a 58,80 m (resistência à penetração).

Optimization of HS-SPME/GC-MS analysis and its use in the profiling of illicit ecstasy tablets (Part 1)

A headspace solid-phase microextraction procedure (HS-SPME) was developed for the profiling of traces present in 3,4-methylenedioxymethylampethamine (MDMA). Traces were first extracted using HS-SPME and then analyzed by gas chromatography-mass spectroscopy (GC-MS). The HS-SPME conditions were optimized using varying conditions. Optimal results were obtained when 40 mg of crushed MDMA sample was heated at 80 °C for 15 min, followed by extraction at 80 °C for 15 min with a polydimethylsiloxane/divinylbenzene coated fibre. A total of 31 compounds were identified as traces related to MDMA synthesis, namely precursors, intermediates or by-products. In addition some fatty acids used as tabletting materials and caffeine used as adulterant, were also detected. The use of a restricted set of 10 target compounds was also proposed for developing a screening tool for clustering samples having close profile. 114 seizures were analyzed using an SPME auto-sampler (MultiPurpose Samples MPS2), purchased from Gerstel GMBH & Co. (Germany), and coupled to GC-MS. The data was handled using various pre-treatment methods, followed by the study of similarities between sample pairs based on the Pearson correlation. The results show that HS-SPME, coupled with the suitable statistical method is a powerful tool for distinguishing specimens coming from the same seizure and specimens coming from different seizures. This information can be used by law enforcement personnel to visualize the ecstasy distribution network as well as the clandestine tablet manufacturing.

LC-MS/MS based assay and reference intervals in children and adolescents for oxysterols elevated in Niemann-Pick diseases.

BACKGROUND: Niemann-Pick type C (NP-C) is a rare progressive neurodegenerative lipid storage disorder with heterogeneous clinical presentation and challenging diagnostic procedures. Recently oxysterols have been reported to be specific biomarkers for NP-C but knowledge on the intra-individual variation and on reference intervals in children and adolescents are lacking. METHODS: We established a LC-MS/MS assay to measure Cholestane-3β, 5α, 6β-triol (C-triol) and 7-Ketocholesterol (7-KC) following Steglich esterification. To assess reference intervals and intra-individual variation we determined oxysterols in 148 children and adolescents from 0 to 18 years and repeat measurements in 19 of them. RESULTS: The reported method is linear (r>0.99), sensitive (detection limit of 0.03 ng/mL [0.07 nM] for C-triol, and 0.54 ng/mL [1.35 nM] for 7-KC) and precise, with an intra-day imprecision of 4.8% and 4.1%, and an inter-day imprecision of 7.0% and 11.0% for C-triol (28 ng/ml, 67 nM) and 7-KC (32 ng/ml, 80 nM), respectively. Recoveries for 7-KC and C-triol range between 93% and 107%. The upper reference limit obtained for C-triol is 40.4 ng/mL (95% CI: 26.4-61.7 ng/mL, 96.0 nM, 95% CI: 62.8-146.7 nM) and 75.0 ng/mL for 7-KC (95% CI: 55.5-102.5 ng/mL, 187.2 nM, 95% CI: 138.53-255.8 nM), with no age or gender dependency. Both oxysterols have a broad intra-individual variation of 46%±23% for C-triol and 52%±29% for 7-KC. Nevertheless, all Niemann-Pick patients showed increased C-triol levels including Niemann-Pick type A and B patients. CONCLUSIONS: The LC-MS/MS assay is a robust assay to quantify C-triol and 7-KC in plasma with well documented reference intervals in children and adolescents to screen for NP-C in the pediatric population. In addition our results suggest that especially the C-triol is a biomarker for all three Niemann-Pick diseases.

Determinação de fósforo orgânico em águas de produção petrolífera por ICP- AES e ICP- MS após pré-concentração em coluna de sílica-C18

Results on the optimization of analytical methods for the determination of phosphorus in phosphino-polycarboxylate (PPCA), used frequently as scale inhibitor during oil production, by ICP-AES and ICP-MS are presented. Due to the complex matrix of production waters (brines) and their high concentration in inorganic phosphorus, the separation of organic phosphorus prior to its determination is necessary. In this work, minicolumns of silica immobilized C18 were used. Optimization of the separation step resulted in the following working conditions: (1) prewashing of the column with methanol (80% v/v); (2) use of a flow rate of 5 mL/min and 10 mL/min, respectively, for the preconditioning step and for percolation of the water sample; (3) final elution of organic phosphorus with 7 mL of buffer of H3BO3/NaOH (0.05 M, pH 9) with a flow rate of 1 mL/min. Sample detection limits (3s) for different combinations of nebulizers and spectrometric methods, based on 10 mL water aliquots, are: ICP-AES -Cross flow (47 mg/L) and Ultrasonic (18 mug/L); ICP-MS -Cross flow (1.2 mug/L), Cyclonic (0.7 mug/L) and Ultrasonic (0.5 mug/L). Typical recoveries of organic phosphorus are between 90 and 95% and the repeatability of the whole procedure is better than 10%. The developed methodology was applied successfully to samples from the oil-well NA 46, platform PNA 2, Campos basin, Brazil. Assessment of the PPCA inhibitor was possible at lower concentrations than achieved by current analytical methods, resulting in benefits such as reduced cost of chemicals, postponed oil production and lower environmental impacts.

Ambientes protegidos e substratos com doses de composto orgânico comercial e solo na formação de mudas de Jatobazeiro em Aquidauana-MS

O Cerrado brasileiro possui inúmeras espécies frutíferas com potencial econômico para exploração em cultivo comercial. Neste contexto, desenvolveu-se um experimento com mudas de jatobá-do-cerrado na Universidade Estadual de Mato Grosso do Sul, em Aquidauana - MS, de 29-outubro-2009 a 25-fevereiro-2010, em estufa agrícola coberta com filme de polietileno de 150 μm, difusor de luz, possuindo tela termorrefletora de 50% sob o filme e fechamentos laterais e frontais com tela de monofilamento, malha para 50% de sombreamento e viveiro com tela preta de monofilamento para sombreamento de 50%, fechamento em 45º. Nesses ambientes, as mudas foram formadas em vasos plásticos de 5,0 L, preenchidos com 100% de solo, 100% de composto orgânico e as doses de 10; 20; 30; 40; 50; 60; 70; 80 e 90 de composto orgânico adicionadas ao solo. Utilizou-se um delineamento inteiramente casualizado, em esquema de parcelas subdivididas, com cinco repetições. Em ambos os ambientes de cultivo, as plântulas emergiram mais rapidamente, com maior crescimento e acúmulo de biomassa em substrato sem adição de composto orgânico. As plântulas do substrato sem composto orgânico desenvolveram-se melhor na estufa agrícola. As mudas do jatobá-do-cerrado não apresentaram resposta positiva em relação ao aumento das doses do composto orgânico. O composto orgânico utilizado aumentou o pH dos substratos, apresentou excesso de certos nutrientes e não contribuiu para um crescimento efetivo das mudas.